Issue 97.3

Yale Scientific

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

OCTOBER 2024

VOL. 97 NO. 3 • $6.99

16

A DEEP DIVE

INTO ANGLERFISH

PATHOGENS SET SAIL 12

ION THE PRIZE 14

19

INSIDE MULTIPLE SCLEROSIS

UPPING THE ANTI 22

TABLE OF

VOL. 97 ISSUE NO. 3

COVER

16

A R T

I C L E

Deep Dive

Patrick Wahlig and Brandon Quach

Millions of years ago, a single common ancestor gave rise to over two hundred species of anglerfish,

each uniquely adapted to thrive in the darkest depths of the ocean. Using phylogenetic reconstruction

techniques, Yale researchers have discerned the impact of ancient climate events on this rapid explosion

of anglerfish speciation. Further genetic analysis reveals the unique—and rather clingy—methods that

anglerfish use to survive in the midnight zone.

12 Pathogens Set Sail

Madeleine Popofsky

We often reduce infectious disease histories to their first introduction and overlook the complexities.

New research challenges this tendency by modeling how diseases like measles and smallpox spread on

ships, revealing slower and more intricate transmission patterns than previously assumed. By analyzing

factors such as population size and travel times, the model offers insights into the unpredictable

journey of diseases across oceans, reshaping our understanding of historical outbreaks.

14 Ion the Prize

Kenny Cheng

As demand for critical transition metals rises in the electronics industry, innovative solutions to provide

an alternative supply are needed. One alternative source, resource recovery, faces technical challenges

in extracting metal ions from contaminated waste streams. To address these hurdles, Yale researchers

propose new membrane designs, offering a potential breakthrough in selective ion separation.

19 Inside Multiple Sclerosis

Risha Chakraborty and Crystal Liu

The immune system is the human body’s defense against all things pathogenic—bacteria, viruses,

parasites. However, when our cellular soldiers turn against ourselves, we develop autoimmune disorders,

such as multiple sclerosis. The Hafler Lab at Yale performed multi-omic analyses on immune cells of

multiple sclerosis patients and healthy participants to shed light on the molecular basis of this disease.

22 Upping the Anti

Max Watzky

Matter and antimatter are two sides of the same coin—so why do we only see the former? The STAR

collaboration has spent decades investigating this question, searching for new ways to put antiparticles

together. Recently, they created the largest nucleus of antimatter ever seen. Their finding probes the question

of matter-antimatter asymmetry and the fundamental logic that defines our universe.

2 Yale Scientific Magazine October 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

How do we fight the fungal apocalypse threatening

bananas? • Justin Zhang

How did the thorns on nightshade plants form? • Toler Poole

Don't Look Behind You • Samantha Feingold

Shockingly Clean • Anthony Wilson

Formula or Breast Milk? • Sarah Sattar

Food Savers • Eric Song

A Shell-Shocking Discovery • Michelle So

A Girl, a Scientist, and the Unknown • Vicky Tan and

Gabriella Umboradak Nanjo

Poison or Cure? • Aiden Zhou

The Trojan Horse, Reimagined • Sarah Li

Liquid Assets • Makena Senzon

Inclusive Images • Brandon Ngo

The Lotus Effect • Michael Sarullo

Hue's the Thing... • Annli Zhu and Dereck Ka-Hon Tran

Please Beehave! • Jordan Thomas

The Hurricane Whisperer • Jiya Mody and Ephraim Cho

Undergraduate Profile: Nikita Paudel (YC '25) • Lynn Dai

Alumni Profile: Jacob Eldred (YC '24) • Chloe Alfonso

Science in the Spotlight: Unveiling the Secrets of Aging • Annie Ye

Science in the Spotlight: Quirks & Quarks • Victoria Tan

Counterpoint: Unveiling Chicxulub • Hannah Dirsa

Crossroads: Data Science for Political Campaigns • Alyssa Anderson

www.yalescientific.org

October 2024 Yale Scientific Magazine 3

HOW DO WE FIGHT THE

FUNGAL APOCALYPSE

THREATENING BANANAS?

&

HOW DID THE THORNS ON

NIGHTSHADE PLANTS FORM?

By Toler Poole

Nightshades refer to a group of flowering plants that

grow year-round, ranging from herbs to small trees.

Some are dangerous—the toxic belladonna, poisonous

angel’s trumpet, and alluring red-berried bittersweet—and

some are consumed by people all the time—tomatoes, potatoes,

and eggplants. These staple crops belong to the Solanum

genus, part of the Solanaceae (nightshade) family. While some

nightshades have thorns, the Solanum crops we encounter in the

supermarket don’t. But could even these harmless nightshades

become problematic by also turning prickly?

Prickles are not the same as those classic thorns seen on

roses. Prickles come from the epidermis or cortex of the plant,

whereas thorns are modified stem tissue. The purpose of

prickles in plants ranges from climbing and defense to water

retention. Prickles emerged from the genus Solanum about

about six million years ago. Specifically, disruption in LONELY

GUY (LOG) genes, which encode enzymes that aid in cytokinin

biosynthesis—the production of plant hormones that contribute

to development—has been associated with prickle loss. LOG

genes play a part in cell proliferation and differentiation.

When these genes or other prickle-related genes are affected or

mutated, the result is a prickle-less phenotype.

A Science article published in August details how scientists

used CRISPR-Cas9 to assess the possibility of editing the LOG

gene so that the plants artificially lack prickles. This could

be beneficial to farmers who do not want to grow crops with

prickles. By genetically engineering these nightshade plants,

the food we buy will be harmless, and farmers will no longer

need to worry that the eggplants they grow will hurt their

customers. less phenotype

■

By Justin Zhang

Some fungi show up in our diets, while others are capable

killers, possessing the potential to wipe out entire

species. The Gros Michel banana, sweeter and less prone

to bruising, was wiped out in the 1950s by a fungus called

Fusarium oxysporum f. sp. cubense Tropical Race 1 (Foc TR1).

While Foc TR1 is no longer a threat, a new race called Foc

TR4 is threatening to repeat history. Foc TR4 causes Fusarium

wilt, a disease that clogs nutrient-delivering pathways in plants.

It grows in infected plants in the xylem, the nutrient- and

water-delivering pipeline, leading to rotting and causing plant

mortality rates between fifty and eighty percent. Acting within

a species complex—a group of closely related strains that

appear alike—Foc can infect over one hundred types of crops.

Each strain has a shared core genome and a unique accessory

genome, which makes it a niche pathogen for specific plants.

In a study published in Nature, scientists compared thirtysix

strains of Foc, finding that Foc TR4 was the most potent

inducer of Fusarium wilt. Through genome sequencing, the

researchers discovered that Foc TR4’s accessory genome allows

it to produce and detoxify nitric oxide, a noxious gas. They

found that disabling the genes responsible for nitric oxide

production and detoxification reduced Foc TR4’s virulence

significantly.

By targeting Foc TR4’s nitric oxide defense mechanisms,

scientists could weaken the fungus and reduce its threat

to bananas. This could involve genome editing, fungicide

development, or genetic modification of the bananas to resist

the wilt or the effects of nitric oxide, offering new ways to

protect bananas from extinction. ■


The Editor-in-Chief Speaks

DIVERSIFYING OUR COVERAGE

In August, our Community Coordinator, Samantha Liu, compiled several statistics

from the last three issues of the Yale Scientific (Volume 96, Issues 1-3). The results

are published below:

“From a survey of the past calendar year, eighty percent of published YSM articles

were written about male scientists, meaning that they were either the first author

or the principal investigator. For sections covering non-Yale research, eighty-seven

percent originated from Western institutions, either in the United States or Europe.

For U.S.-based research, nearly all papers originated from Ivy League institutions,

MIT, or the UCs. The thirteen percent of non-Western sources were all from

developed countries in Asia.”

Historically, science has favored researchers who are white, male, and affiliated

with elite institutions. These researchers traditionally receive the most funding and

coverage in high impact factor journals and social media outlets, such as Nature and

The New York Times, fueling a cycle that has been reflected in YSM’s coverage. We

recognize that we have work to do to combat these harmful biases. With Samantha’s

guidance, we have begun to reconfigure our pitching process to spotlight research

published by institutions in the Global South, historically Black colleges and

universities, and labs led by women and people of color.

In Volume 97, Issue 3, we highlight the contributions of traditionally underrepresented

groups in science. In Full-Lengths, we report on research conducted

by Yale E&EB graduate student Elizabeth Blackmore. Blackmore’s work delves into

the sea-borne transmission patterns of pathogens like smallpox and measles, which

are deeply entrenched in the global histories of trade and colonialism (pg. 12). In

Features, we foreground Project Prakash, an organization that aims to restore vision

to children in India with congenital cataracts and other forms of treatable blindness

(pg. 28). We also introduce readers to atmospheric scientist Rosimar Rios-Berrios,

whose childhood in Puerto Rico’s “Hurricane Highway” galvanized her to find a way

to predict hurricanes weeks in advance (pg. 32). In Special Sections, we feature Nikita

Paudel (YC ’25), who founded an educational company called Pyari to destigmatize

menstruation in Nepal (pg. 34), while in News, we uncover an innovative way to filter

nitrates from water, potentially increasing global access to clean drinking water (pg. 6).

Our work to diversify our coverage is ongoing. We want to emphasize that this is

the beginning of a much longer reckoning, which will require diligence and careful

research. We extend our gratitude to all of the YSM masthead members, contributors,

and advisers who have dedicated their labor and care to the magazine and hope that

we can collaborate to ensure that this critical work extends far into the future.

About the Art

Hannah Han, Editor-in-Chief

At first glance, the sharp teeth, long

spines, bulging eyes, and dark habitat

of the anglerfish do not scream “love.”

But these deep-sea dwelling creatures

possess two unique mating habits—

sexual parasitism and immune gene

degeneration—that enable them to

survive in the midnight zone. The

romantic pinks and purples of this piece

capture how love finds a way to flourish

even in the most hostile environments.

Annli Zhu, Cover Artist

MASTHEAD

October 2024 VOL. 97 NO. 3

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

Wyatt Aiken

Chloe Alfonso

Julien Amsellem

Alyssa Anderson

Justin Baldassarre

Gabriela Berger

Andre Botero

Risha Chakraborty

Kenny Cheng

Michelle Cheon

Lynn Dai

Sara de Ángel

Hannah Dirsa

Samantha Feingold

Ian Gill

Daniel Havlat

Sarah Heebe

Sophie Heitfield

Melody Jiang

Patricia Joseph

Genevieve Kim

Joelle Kim

Paul-Alexander Lejas

Crystal Liu

Nyla Marcott

Leah Mock

Kenna Morgan

Lee Ngatia Muita

Brandon Ngo

Kimberly Nguyen

Luke Parish

Toler Poole

Ethan Powell

Malina Reber

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

Jake Robbins

Alondra Moreno

Santana

Makena Senzon

Michelle So

Nikolai Stephens-

Zumbaum

Victoria Tan

Lynna Thai

Ellie Tillman-

Schwartz

Hien Tran

Melda Top

Max Watzky

Anthony Wilson

Annie Ye

Aiden Zhou

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

Psychology / Engineering

DON’T LOOK

BEHIND YOU

UNDERSTANDING HOW

PARANOIA ARISES IN THE BRAIN

BY SAMMY FEINGOLD

SHOCKINGLY

CLEAN

ELECTRIFIED MEMBRANES

FILTER NITRATES

FROM DRINKING WATER

BY ANTHONY WILSON

PHOTOGRAPHY BY SARAH HEEBE

IMAGE COURTESY OF PICKPIK

Have you ever wondered what causes that queasy feeling

that others might be out to get you? Researchers call this

feeling paranoia, and it is believed to stem from one’s

inability to adapt to new situations. Paranoia is associated with

disruptions in volatility beliefs—our expectations of change. A

study led by Praveen Suthaharan, a graduate student in Yale’s

Interdepartmental Neuroscience Program, sought to identify the

brain regions responsible for volatility beliefs.

His team explored two contenders: the orbitofrontal cortex

(OFC), linked to adaptive behavior, and the magnocellular

mediodorsal thalamus (MDmc), which is associated with

reward learning. Monkeys with lesions of either the OFC

or the MDmc were presented with options on a screen, with

one choice yielding a reward for the fewest clicks. The catch:

the reward probability per choice eventually reversed—a task

called the probabilistic reversal learning task. Computational

modeling was used to relate the monkeys’ behavior to human

decision-making patterns.

The MDmc-lesioned monkeys demonstrated heightened

volatility beliefs and switched choices after selecting the “winning”

choice. In contrast, OFC-lesioned monkeys continuously clicked

the least-rewarding choice, indicating decreased reward learning.

The researchers implicated the mediodorsal thalamus in causing

human paranoia based on the volatility impairments displayed.

“I’m excited about how this cross-species approach helps us

understand the link between the brain’s biology and the mind’s

experience. It’s a crucial step toward improving our understanding

of psychiatric conditions and will guide future mental health

research,” Suthaharan said. The next time you look over your

shoulder with apprehension, ask yourself if someone is truly

there, or if your unsubstantiated volatility beliefs are to blame. ■

Access to clean drinking water may feel like a given in the

United States, but a variety of contaminants lurk beneath

the surface of our water sources. In particular, when

present in water sources at high levels, nitrates—compounds

commonly found in fertilizer, sewage, and manure—are often

associated with birth defects and death of aquatic life. The US

Environmental Protection Agency (EPA) sets the nitrate limit at

ten milligrams per liter, yet the metal catalysts currently used to

remove nitrate can cause another form of contamination when

dissolved in water.

A research team led by postdoctoral associate Yingzheng

Fan from the Winter Lab investigated a new nitrate cleaning

system: nanoporous electrified membranes containing carbon

nanotubes (CNT-EMs). These CNT-EMs are composed of

interlaid stacks of carbon nanotubes arranged in cylindrical

shapes, creating tiny gaps known as nanopores. The team

discovered that these membranes were not only more efficient

than the current alternatives but also demonstrated greater

long-term stability. With a filtration time of just fifteen

seconds, they achieved eighty percent nitrate conversion.

What makes this research even more fascinating is its

relevance to Yale and New Haven itself. The water tested in the

paper was gathered from Lake Wintergreen, located less than

five miles away from Yale’s campus. “I want to incorporate

this membrane into large-scale filtration setups and hopefully

try different locations,” Fan said. Although CNT-EMs are

still in their early stages of development, the initial results

are promising. More importantly, this research reveals the

complex work behind ensuring access to something many take

for granted—clean drinking water. ■


Women’s Health / Sustainability

NEWS

j

GOT MILK?

THE EFFECTS OF FORMULA VS.

BREAST MILK ON

INTESTINAL DEVELOPMENT

BY SARAH SATTAR

FOOD FOR

THOUGHT

YALE UNVEILS DINING HALL

AI INITIATIVES TO REDUCE

FOOD WASTE

BY ERIC SONG

IMAGE COURTESY OF PEXELS

PHOTOGRAPHY BY AMY BOOTE

It’s a question at the forefront of many mothers’ minds:

Is it better to breastfeed or formula feed my child? This

choice is particularly crucial for premature infants, who

are predisposed to necrotizing enterocolitis (NEC), a lifethreatening

illness that causes the intestines to experience

severe inflammation. Researchers at the Yale School of

Medicine analyzed the effects of various diets on organoids—

cells artificially grown to mimic an organ—derived from fetal

tissue similar in age to that of an extremely preterm infant.

In the study, the organoids were treated with one of four

types of milk. Parental milk was unpasteurized. Donor

human milk was pasteurized, as it would be from a milk bank,

which denatures potentially beneficial proteins. Standard

formula was the formula full-term infants would usually

drink. Partially hydrolyzed formula was the formula easier

for babies to digest. The results revealed that human milk,

especially parental milk, had the most benefits for intestinal

health, as it supported both growth and differentiation of

essential intestinal cell types in the organoids.

While human milk is most beneficial for preterm infants’

gut health, social and economic factors can make its provision

difficult, especially due to limited maternity leave and the

high costs of donor milk. Neonatologist and physicianscientist

Liza Konnikova expressed the need for more support

for employed mothers through better maternity leave policies

and enhanced hospital support for families. Further research

can also help determine what specific factors make human

milk more beneficial. “If we can supplement the formula with

healthier factors that the milk makes, those babies could also

grow better,” Konnikova said. ■

Sitting down for a meal at the dining hall may seem like

an inconsequential part of every Yale student’s daily

routine. But when the leftovers of our meals are tallied

up, the impact is striking. The US Department of Agriculture

estimates that thirty to forty percent of food is wasted

nationwide. Every day, approximately twelve thousand meals

are doled out by Yale Hospitality across dining facilities on

campus. No matter how good the Yale dining hall food is,

waste is inevitable.

However, Yale believes we can do better. Beginning on

March 1, the Yale Hospitality Culinary Support Center

and all residential dining hall kitchens implemented AI

technology as part of a new sustainability initiative to

reduce food waste. Daniel Flynn, director of asset renewal

at Yale Hospitality, describes the system as an aid to making

sustainable purchasing decisions for dining halls.

The system operates as follows: when food waste is

discarded, AI-powered cameras and scales keep track of

the disposed food items. This information is then used to

optimize how food is purchased, prepared, and served,

allowing for more efficient use of ingredients. “It’s similar to

the previous system in terms of convenience,” one diner at

Timothy Dwight College’s dining hall said.

But how effective is this system? In April, the new

technology was used behind the scenes in the dining hall

kitchens and central culinary center, greatly reducing food

waste. At the beginning of fall 2024, a front-of-house system

was introduced in Timothy Dwight College’s dining hall as a

trial run. Ultimately, Yale’s goal is to decrease food waste by

twenty percent in 2024 and thirty percent in 2025. With the

assistance of AI, this seems more possible than ever. ■



FOCUS

Energy

A SHELL-SHOCKING

DISCOVERY

How Giant Clams

Became Our Best

Solar Panels

BY MICHELLE SO

IMAGE COURTESY OF FLICKR

The most efficient solar energy farm might not look like what

you’d imagine. There are no acres of flat desert, no industrialsized

mirrors or refrigerator-sized batteries. Rather, in the

crystalline waters of Palau, the giant clam Tridacna boasts a peculiar

trait—near sixty-seven percent optimal photosynthesis. As strange

as it sounds, these irregular creatures may possess the anatomy to

conduct the most efficient form of photosynthesis currently known.

Clams are members of the bivalve family—organisms that are

bilaterally symmetrical with an “in” siphon and an “out” siphon.

As they take in and expel water, clams capture vital foods such as

microscopic plankton. However, the clear waters of Palau are not the

best areas to filter-feed for these small critters. Imagine trying to bob

for apples in the Great Lakes…not effective!

So, to sustain itself, the giant clam possesses a unique anatomical

structure: a stunningly iridescent mantle filled with special

photosynthetic algae. The pairing is evolutionarily elegant; the algae

provide the clam with sugars from photosynthesis, and the the clam

upholds its end of the bargain by contributing nitrogen and other

nutrients to the algae. What makes the clam’s structure interesting isn’t

just this symbiotic relationship, but its efficiency. Food crops grown

under high solar energy, similar to the tropical environment of the

clam, only convert around three percent of the energy in sunlight

into usable sugars. Then, what is the secret behind the giant clam’s

solar efficiency?

“As it turns out, the algae inside the clam tissue are organized in a very

specific geometry, kind of like they’re in these cylindrical pillars. Like

spaghetti pillars growing straight toward the sun,” said Amanda Holt,

a Yale physicist and co-author of the study published in PRX: Energy.

During Holt’s post-doc at UCSB, she came to appreciate the

interdisciplinary collaboration used to investigate interesting optical

properties of marine animals and how they could be applied to

new technologies. It was there that Holt met Alison Sweeney, a Yale

professor of ecology and evolutionary biology and physics, and they

began working on clam biophysics together. The two eventually

moved to Yale, where Holt currently works as an associate research

assistant in Sweeney’s lab. Her lab focuses on the interaction of light

with biological materials, like the clam tissue, and how these materials

naturally evolve.

Along with third co-author Lincoln Rehm, who is Palauan-American,

the researchers created a model to calculate the clam’s quantum

efficiency, or the ability to convert photons into electrons. The clam

contains layers of spherical cells called iridocytes, which scatter sunlight

outward into a cone-like shape. This conical beam of diffused light

then reaches the columns of algae, which are nearly perfectly aligned

to receive the light. Everything about this system works in tandem to

maximize the output. Being exposed to such strong sunlight can be

damaging to molecules, which is why diffusing the light is essential to

preserve the integrity of the proteins involved.

What they found was that the tissues had a forty-two percent

quantum efficiency, a number significantly greater than the fourteen

percent efficiency boasted by terrestrial photosynthetic plants in

the same region. But the team took their model one step further,

accounting for the clams’ daily movement; as the sun changes position

throughout the day, the clam readjusts and spreads out its fleshy mantle

to account for this fluctuation. The new calculation came out to around

sixty-seven percent.

Holt said these findings hold major applications across numerous

industries. Algae compounds are incorporated into various products,

including cosmetics, foods, and, most importantly, fuel. By creating

tiny devices mimicking the pillar-like geometry of the giant clam’s

algae, growers can maximize algal production for commercial use.

It’s worth noting that several species of Tridacna clam are listed as

protected species due to habitat threats and climate change. Valued

highly for their ivory-like shells, these centuries-old organisms have

also become victims of poaching. Because of their conservation status,

Holt said that researchers would purchase giant clams from local

farmers and perform tissue biopsies in the lab, rather than collect

specimens from the wild.

With these bountiful applications, it’s no surprise that unsuspecting

consumers may soon reap the benefits of the remarkable giant clam,

whether for algal-based cosmetics, food additives, or even the energy

powering our homes. ■


Medicine

FOCUS

A GIRL,

A SCIENTIST,

AND THE

UNKNOWN

The Story Behind PI3Kγ

BY GABRIELLA UMBORADAK NANJO

AND VICKY TAN

IMAGE COURTESY OF MATT BRADBURY COMMUNICATED BY MARYAM TWAHIR

Like all big discoveries, this one begins with a story. Carrie

Lucas, an associate professor at the Yale School of Medicine,

first learned about a young girl who had abnormal blood

cell levels through her clinical colleagues at the National Institutes

of Health (NIH). The girl later developed trouble breathing and

diarrhea. Lucas was intrigued because the patient’s immune disease

had two components: immunodeficiency and inflammation. The

girl’s antibody levels were low, which caused her to suffer from a

cycle of reinfection in her lungs. She also had inflammation in her

gut and lungs. Previously, her doctors gave her anti-inflammatory

drugs and antibodies to increase her defenses against infection.

The girl’s immune system was malfunctioning, but it wasn’t clear

how or why. Our immune system consists of the innate and the adaptive

system. The innate system recognizes invading microorganisms

and responds to pathogens quickly. However, these initial defenses

are sometimes not enough, so the innate system communicates with

the adaptive system to mount a more specific response to an invading

microbe. B cells are a part of the adaptive system. They are a type

of white blood cell that can transform into antibody-secreting cells

(ASC). The B cell receptors (BCR) on their surface recognize and

bind to antigens—foreign molecules in our bodies. Once BCRs are

secreted by ASCs, they are referred to as antibodies. Antibodies, “Y”-

shaped proteins that recognize and bind to intruding antigens, block

microbes from causing infections and alert the immune system to

attack the foreign substance.

Lucas, whose lab focuses on children with rare genetic immune

disorders, was determined to uncover what was happening to the

young girl. After sequencing her genome, Lucas and her team discovered

that the girl had a mutation that causes a decreased production

of phosphatidylinositol 3-kinase-gamma (PI3Kγ), a signaling

molecule in the immune system. Lucas was fascinated by the unexpected

connection between this molecule and antibody production

since prior knowledge would not have predicted low antibodies

from PI3Kγ deficiency. Further research conducted by scientists in

the lab revealed that PI3Kγ plays a crucial role in the ability of B cells

to become ASCs. “What’s great about this type of discovery is that

it starts with patients with rare diseases who we aim to help by uncovering

why are they sick, both from a genetic and immunological

standpoint, and it advances to a better understanding of the fundamental

biology of how our immune systems work, offering opportunities

to apply that new knowledge across a range of disease context,”

Lucas said.

To determine that this mutation was responsible for the young girl’s

symptoms, the Lucas Lab used a mouse model that lacked the PIK3CG

gene, which encodes PI3Kγ. As a first assessment, they co-housed the

lab mice with mice from a pet store. Unlike lab mice, which have a very

‘clean’ microbiome due to the controlled laboratory environment, petstore

mice possess a more diverse gut microbiome developed through

more interactions with the natural environment and other animals.

Taking into account the fact that gut microbiota have a major impact

on immune cells was important when imitating human PI3Kγ deficiency.

Co-housing the lab mice with the pet store mice simulated

those external factors in the human patient’s environment that could

be implicated in the development of disease symptoms. They found

that the lab mice with the deficient gene developed symptoms similar

to those of the human patient, establishing a causal relationship between

the gene loss and the disease symptoms.

These findings can potentially be applied to a wide range of diseases.

Lucas highlighted diseases like lupus and rheumatoid arthritis, in

which the immune system mistakenly reacts against the body’s healthy

cells. “Some of these diseases are characterized by antibodies that bind

to your tissues, so it raises the idea that now that we have learned from

this rare disease that PI3Kγ is so important for the step of becoming

an ASC, maybe we could help patients who have antibody-mediated

disease by inhibiting this [signaling molecule] so disease-causing antibodies

are reduced,” Lucas said. From the discovery of a rare mutation

in a single patient to the dedicated research in Yale’s labs, this story

emphasizes the potential for patient-driven research to produce great

advances in knowledge and, in the long run, new avenues for treatment

options for a range of diseases. ■



FOCUS

Botany

POISON OR

CURE?

The Search for the

Hellebore Plant

BY AIDEN ZHOU

PHOTOGRAPHY BY AIDEN ZHOU

Upon graduating from medical school, physicians often recite

modern versions of the Hippocratic Oath, which famously

contains the promise to “do no harm.” Today, this measure is

purely ceremonial—rarely do doctors wish to hurt their patients. In

Ancient Greece, however, the notion of harm and healing were often

intertwined. The Greek word pharmakon captures this duality—it

does not refer exclusively to prescribing remedies, but it encompasses

the dual notions of healing and hurting, poisons and cures.

Hellebore, a delicate flower famed in Greek culture, typifies this

duality. While it was known to be a popular pharmaceutical product

in antiquity, its exact applications and effects have now been lost.

Oddly, hellebore is also a fatal poison. Implicated in the death of

Alexander the Great and used by Nebros, an ancestor of Hippocrates,

to poison the city of Kirrha’s water pipes, the “winter rose” has had a

dubious yet unquestionably decorated history.

To investigate the nature of hellebore, the Yale Ancient Pharmacology

Program (YAPP) traveled to Antikyra this summer. Led by Andrew J.

Koh, the program’s director and a Museum Scientist at the Peabody

Museum, YAPP is a unique research team. Aiming to study “ancient

pharmacology,” the program combines a variety of methodologies,

merging ethnographic observations and chemical analysis with

innovative ideas from machine learning and drone technology.

Micah Gold (YC ’24) was a part of the Greek expedition and has

been contributing to the technological aspects of YAPP’s research

since his first year. His early work focused on recognizing and

identifying pottery using multispectral imaging. “The idea is that

when sunlight hits pottery, it reflects different spectra than rock,”

Gold explained. “And if we use our multispectral drone at the right

frequencies, we can pick out that difference.”

This summer Gold traveled to Antikyra, an ancient port city that

used to be well-known for its hellebore treatments, hoping to apply

his skills in the team’s search. “Historically, Antikyra seems to be a

sort of sanatorium for recovering individuals. People would travel

from all across the world to Antikyra to do a hellebore treatment,”

Gold said.

YAPP aimed to find local hellebore specimens and figure out why

the plant was so desired. It wasn’t easy: the team contacted medicine

men and local farmers and hiked for miles up Mount Helicon. But

after three days of searching, it happened. “We finally found this large

quantity of hellebore and were able to take samples,” Gold said.

With these samples, Gold and other technicians in the YAPP team

trained their drones on the multispectral and thermal signatures of

hellebore. Similar to how they located pottery, they used the data to

detect these plants from the sky, avoiding more arduous journeys in

the future.

Coming back from this successful expedition, YAPP has more

options than ever as they get ready to explore the implications of their

findings. Modern drug discovery today is focused on the process of

exhaustion, akin to throwing a proverbial kitchen sink at any given

problem. This approach, called high-throughput screening, uses

machine learning to run through millions of pharmacological tests,

creating combinations of chemical compounds that just might work.

YAPP’s research aims to take a different, more economical approach

to drug discovery. “Why don’t we have a concerted effort to use the

knowledge of past botanicals, and maybe that can be a better clue to

finding the next life-saving drug?” Gold asked.

In addition to presenting us with possibilities for medical innovation,

uncovering clues from the past can also help us learn about how

humans used to live. Was hellebore truly used to cure madness and

indigestion? Did Emperor Caligula use it during Roman times? There

are many questions left unanswered. “It might be the case that the

hellebore we’re studying doesn’t have any special properties because it

might be the case that the hellebore we’re studying is not even the right

species,” Gold said. “It could be that that species has gone extinct.”

According to locals, there are at least two other types of the plant that

YAPP has not yet found.

The YAPP team’s quest for hellebore will continue next year with

the additional support of Yale botanists, including Patrick Sweeney

from the Peabody Museum. Their efforts could potentially reveal

discoveries about both the ancient world and the present day. ■


Molecular Biology

FOCUS

THE TROJAN

HORSE,

REIMAGINED

Fighting Cancer

from the Inside Out

BY SARAH LI

PHOTOGRAPHY BY LUKE PARISH

Picture this: a group of ancient warriors hiding inside a massive

wooden horse, ready to infiltrate a fortified city. When the

unsuspecting guards bring the horse inside, the warriors leap out

and take over from the inside. This is the story of the Trojan Horse, and

believe it or not, postdoctoral associate Fei Cao and associate professor

James Hansen at the Yale School of Medicine Department of Therapeutic

Radiology have found a way to use this tactic against cancer cells with a

groundbreaking new therapy.

The heroes in this story are called antinuclear antibodies (ANAs).

Typically, these antibodies play a role in autoimmune diseases like lupus,

where they mistakenly target the body’s own cells. However, researchers

have repurposed these antibodies to infiltrate cancer cells and cause

damage. One of the most remarkable examples of these is Deoxymab-3

(DX3). This antibody is designed to sneak into the nuclei of cancer cells,

where it can enact its destructive potential.

Cancer cells often have multiple defenses that make them difficult to

treat. Many standard therapies rely on targeting specific surface markers

to identify and attack cancer cells. However, this approach can be

limiting, particularly against aggressive tumors that lack these markers.

DX3 associates with the nucleoside (essentially a nucleotide without

the traditional phosphate group) salvage pathway—a recycling process

that converts nucleosides back into nucleotides for cellular processes.

DX3 first enters the cell via nucleoside transporters. As the nucleoside

is brought into the cell for repurposing, DX3 successfully bypasses the

cell membrane and nuclear membrane, entering even the most secure

cancer cells.

Once the DX3-nucleoside transporter complex is inside the nucleus,

it lures an enzyme known as cathepsin B (CatB) into the nucleus. Under

normal conditions, CatB resides in the cytoplasm, where it helps break

down cellular waste. However, when DX3 brings CatB into the nucleus,

the researchers hypothesize a self-defense mechanism is triggered due to

the fact that DX3 itself is toxic to the cancer cells.

In addition to DX3, the scientists developed a next-generation weapon

called an antinuclear antibody-drug conjugate (ANADC). “This approach

combines DX3 with a powerful drug, linked by a chemical fuse that CatB

can sever,” Cao said. When DX3 infiltrates the cancer cell’s nucleus and


draws CatB in, the enzyme activates ANADC precisely where it is needed

by cleaving the link between the drug and DX3, delivering a targeted

attack on the cancer cells. However, if CatB is blocked, ANADC loses its

effectiveness, emphasizing the enzyme’s critical role in this therapy.

What sets ANADC apart is its tumor-agnostic nature, meaning that

it has the potential to address a wide range of cancers, regardless of their

individual characteristics. Unlike traditional treatments that depend on

specific markers, ANADC targets the DNA and nucleosides released by

dead or dying tumor cells.

Researchers have tested this innovative strategy against brain cancer

modeled in mice with impressive results. One of DX3’s standout features is

its ability to cross the blood-brain barrier (BBB), a major obstacle for many

therapies. The BBB, a filter-like membrane between the blood and brain,

protects the brain from harmful substances but also prevents most drugs

from reaching it. DX3 uses nucleoside transporters to navigate this barrier,

allowing it to potentially treat difficult-to-reach brain tumors like gliomas.

In laboratory studies and mouse models, ANADC has demonstrated

its ability to penetrate cancer cells effectively, leading to substantial tumor

destruction. It not only slows tumor growth but also extends survival

rates without harming healthy tissues. This is a significant advancement,

as many conventional treatments, such as chemotherapy, often damage

healthy cells and lead to severe side effects.

Cao and Hansen’s work offers a novel approach to cancer therapy,

transforming antinuclear antibodies into effective agents that can infiltrate

and destroy cancer cells from within. By leveraging DX3’s ability to lure

CatB into the nucleus, this therapy can potentially target a wide array of

cancers, even those resistant to current treatments. “Cancers such as triplenegative

breast cancer do not have normal cell receptors, so the world can

benefit from this type of therapy,” Cao said. The capability to cross the BBB

and specifically target brain tumors further enhances its potential.

The DX3 antibody is currently patented and already listed in clinical

trials with researchers having high hopes of replicating in humans the

promising results seen in mice. This innovative strategy offers new hope

in the ongoing fight against cancer, with the potential to revolutionize the

way we treat this complex disease and bring us one step closer to a cure.

Watch out, tumor cells! The cure is right behind you. ■


FOCUS

Ecology

PATHOGENS SET SAIL

Modeling the Journey of Diseases Across Oceans

BY MADELEINE POPOFSKY

ART BY HANNAH DIRSA

Measles was first introduced to Fiji in

1875. It died out only six months after

its debut.

The introduction of measles to the Pacific

Islands is often painted as a straightforward

superspreader event, but the reality is that

measles didn’t become the outbreak we know

it as until it was reintroduced in 1903. “There’s

a story of global disease history in the popular

imagination that says diseases spread like wildfire

across the globe once European colonists started

sailing on their ships,” said Elizabeth Blackmore,

a graduate student in the Department of Ecology

and Evolutionary Biology at Yale. However, this

story is an inaccurate one, and her work gives

reason as to why.

A recent paper by Blackmore and James Lloyd-

Smith, a professor of ecology and evolutionary

biology at the University of California, Los

Angeles, deepens our understanding of how

diseases spread across oceans and the likelihood

they will take hold in a population. They seek

to poke holes in popular, yet false, narratives

about disease.

Moving beyond the simplistic notion that

every single case has the potential to spark a

superspreader event, the paper presents a model

that offears a detailed quantitative framework for

analyzing infectious disease spread aboard ships.

A New Approach to Understanding Outbreaks

The model, known as a stochastic Susceptible-

Exposed-Infectious-Recovered (SEIR) model,

aims to quantify the probability of an outbreak

lasting a particular length of time within a

certain population. It was inspired by studies on

epidemics in California, where the researchers

noticed that measles had been introduced

relatively late, in 1806. This unexpected finding

spurred them to develop this mathematical

model to explore the reasons behind it.

“How did it take that long? How did measles

even get to California?” Blackmore said. “How

easily could measles survive on a ship?”

Blackmore described the model as taking

a classic approach. “Because this is the first

general study of how long outbreaks last

onboard ships, we intentionally decided to take

one of the simplest approaches we could think

of,” she explained.

Using established outlooks and parameters

from traditional infectious disease studies,

Blackmore and Lloyd-Smith built their model of

disease spread during transatlantic voyages. This

approach enabled them to quantitatively analyze

events that had previously only been addressed

qualitatively. Their efforts marked the first

time these issues had been evaluated through a

numerical lens.

The model begins by examining susceptibility—

determining whether a given individual within a

population is capable of contracting the disease.

To simplify the initial analysis, the model first

assumes that the entire population is susceptible,

which allows them to create a baseline for their

model. The researchers later explored varying

percentages of susceptible individuals to see

how different levels of immunity could influence

disease transmission patterns.

Next, the researchers incorporated two critical

timeframes: the incubation period, which refers


Ecology

FOCUS

to the time from infection to symptom onset,

and the infectious period, which is the duration

a person can transmit the sickness to others. In

addition, they factored population size into

their model.

Another important element is the

epidemiological parameter, or R 0

, which

represents the average number of infections

caused by a single person in a fully susceptible

population. By manipulating R 0

, the researchers

could observe the dynamics of disease spread.

A very low R 0

indicates that the virus does not

transmit beyond the initial case—thus, the

outbreak lasts only as long as the first person

is incubating the virus. Conversely, when R 0

is very high, the virus continues to spread

among individuals and is only stopped when

herd immunity is achieved—that is, until

enough people are no longer susceptible to

the disease, which ultimately slows down and

can halt transmission. This situation results

in outbreaks that last longer, as the virus has a

larger pool of potential hosts to reach before it

can no longer spread effectively.

Interestingly, the longest outbreaks occur

when R 0

is at an intermediate “critical” value.

Around this range, the outbreak can last up

to thirty times longer than the average length

of an infection in a single individual, though

durations can vary greatly. While R 0

serves as

the foundation for their initial, simpler model,

Blackmore and Lloyd-Smith later refined this

value into the pathogen effective reproduction

number (R e

), a more nuanced representation of

transmission intensity.

Measles in California

Focusing on steamship journeys between

1850 and 1852 to and from a port in San

Francisco, Blackmore and Lloyd-Smith used the

model to analyze the transmission of measles,

influenza, and smallpox, demonstrating how

each disease’s distinct characteristics influenced

their spread.

The model demonstrated that disease

transmission, even via ship travel, can be slow

and depends greatly on specific disease traits. For

instance, influenza has a very low R 0

and very

short incubation and infectious periods; based

on the model’s calculations, only the most rapid

journeys with a high volume of passengers could

have facilitated the introduction of this disease

to California. In contrast, measles, which has

longer incubation and infectious periods, poses

a moderate risk. Smallpox poses a great danger

even on extended journeys due to its prolonged

incubation period. However, its low R e

means

that transmission within a population, and

therefore widespread introduction throughout a

city, is still unlikely.

In addition, the model sheds light on important

historical events. “Even Christopher Columbus’s

famous 1492 journey had a decent chance of

carrying a virus like measles or smallpox across the

Atlantic—if an infected sailor had been among the

crew at departure,” Lloyd-Smith said.

Charting a Path for Future Disease Prevention

Blackmore emphasizes the importance of

viewing infectious diseases through a more

human-centered lens. “You’ll see everywhere

people saying that ships carried disease. And

it makes it sound like the disease is sitting in a

box, along with a whole bunch of other cargo,”

Blackmore said. “I think it’s important to write

histories of infectious disease where we take the

experience of infection seriously.”

The researchers continue to work on validating

the model by comparing its predictions to even

more historical sources, such as ship medical

logbooks and quarantine station records, to test

their confidence in its predictions. Future work

could also improve the model by introducing

more complexity to its components. For example,

instead of assuming everyone in the population

is equally susceptible to a disease, a new model

could take variations in individuals’ susceptibility

into account. Additionally, parameters could

be added to consider that some diseases can

be spread through non-human routes, such as

surface contact or vectors like rats. Finally, the

roles of infected individuals on the ship can also

influence risk levels.

Blackmore hopes to use her research to educate

the public about historical disease transmission.

However, she also emphasizes her work’s relevance

to contemporary issues, such as COVID-19.

“We can’t expect people to believe that social

distancing works if we are telling stories about

how ships spread pathogens across the world like

magic,” Blackmore said.

Modeling infectious disease spread has

important implications for both the past and

present. However, it could also play a key role

in the future. In particular, space travel could be

a perfect candidate for Blackmore and Lloyd-

Smith’s model. “There are strong similarities [to

ships], with small populations of humans aboard

a vessel for extended periods, journeying to new

areas that may not have encountered some of our

human pathogens before,” Lloyd-Smith said.

Blackmore noted that pathogens with longer

lifespans would be especially relevant in space

environments, citing tuberculosis as a prime

example. With potential advancements in space

travel technology, however, it’s possible that even

measles could become a concern.

“If humans establish a colony on Mars, we

would like to avoid introducing pathogens from

Earth if we can avoid it,” Lloyd-Smith said. ■

PHOTOGRAPHY BY WENHE ZHANG

Elizabeth Blackmore, the first author of the paper,

writes the differential equations that form the foundation

of the mathematical model of pathogen transfer.

ABOUT THE AUTHOR

MADELEINE POPOFSKY

MADELEINE POPOFSKY is a junior majoring in Chemistry, B.S. (Intensive). In addition to her roles as

senior staff writer, layout editor, and illustrator for YSM, she performs chemical biology research for

the Slavoff Lab, is a member of the Yale Debate Association, and is the visual arts director for Hippo

Literary and Arts Magazine. She enjoys running, drinking iced coffee in thirty-degree weather, and

eating chocolate.

THE AUTHOR WOULD LIKE TO THANK Elizabeth Blackmore for her time and insightful comments

regarding her research.

REFERENCES:

Blackmore, E. N., & Lloyd-Smith, J. O. (2024). Transoceanic pathogen transfer in the age of sail and

steam. PNAS, 121(20): e2400425121. https://doi.org/10.1073/pnas.2400425121



FOCUS

Environmental Engineering

ION THE PRIZE

Using Bio-Inspired

Membranes to

Recover Critical Metals

BY KENNY CHENG

ART BY MADELEINE POPOFSKY

I

n today’s sustainability-driven world,

resource recovery—the extraction of

valuable materials from waste—has

become increasingly important. Certain

metals, including cobalt, nickel, and copper,

are essential for key sustainable technologies

like electric vehicle batteries and wind

turbines, but their supply is limited. This

scarcity, coupled with a pressing demand, has

earned them the title of ‘critical metals.’

One promising source of critical metals

lies in waste streams, byproducts discarded

from industrial or commercial processes

that often contain significant amounts of

valuable metals. However, recovering metals

from waste streams continues to be difficult

because they are often contaminated mixtures

that require complex separation processes.

“The pressing need for critical metals

necessitates the development of

advanced ion separation

technologies,” said Menachem

Elimelech, Sterling Professor

of Chemical and Environmental

Engineering at Yale. “Traditional

methods are chemical and

energy-intensive, which hinders

the recovery of valuable materials

from waste streams.” Indeed,

finding a more efficient method

to extract valuable metals from waste

mixtures, where these metals exist as

charged particles called ions, would provide

a much-needed solution to the scarcity of

critical metals—and a solution that may

already exist in nature.

In a recent paper published in Nature Water,

researchers from the Elimelech Lab present

innovative new strategies for designing

membranes—thin filters that selectively

allow certain particles to pass while blocking

others—that can be made to extract critical

metal ions from waste streams. Designing

such membranes presents substantial

challenges. Traditional approaches have

relied heavily on two key mechanisms: pore

size and static charge. Membranes can reject

larger ions that are unable to fit through the

tiny holes across their surface, acting like a

sieve. They can also be designed to have a

specific electrical charge on their surface,

generating an electrostatic field that repels

i o n s

of like charges.

But for transition metals like

cobalt, nickel, and copper, this

existing method is inadequate.

“The problem for transition

metal separations, which are so

critical to our transition away from

fossil fuels, is that these metal species

are similar in size and charge,” explained

Camille Violet, a PhD candidate at Yale

and first author of the paper.

To address this, the team has begun

developing membranes inspired by natural

biological systems, chemically tailoring

membrane materials to separate different

critical metal ions.

Bio-Inspired Separation

A key innovation highlighted in the paper

is the design of metal-organic frameworks

(MOFs) as materials for ion separation.

MOFs are crystalline structures composed of

metal nodes and organic ligands—molecules

that link the metal components together.

These frameworks are designed to be highly

porous and customizable, making them an

ideal material for selectively isolating specific

molecules from complex waste mixtures.

To tailor the MOFs for the targeted separation

of ions, the researchers identified several

quantum- and molecular-level properties that

influence ion selectivity. By leveraging these

properties of transition metals, they aimed to

achieve more precise separations.

One such critical property of transition

metals is their hydration shell, which refers to

the layer of water molecules that form around

ions in solution. Some transition metals are

more likely to shed their hydration shells than

others, allowing them to bind more easily

to the membrane. Additionally, the unique

electron arrangements of each transition

metal lead to distinct binding preferences for

specific groups of atoms, known as functional

groups, found on the membrane surface. For

instance, copper ions tend to adopt a specific

geometry due to a phenomenon called Jahn-

Teller distortion, differentiating them from

cobalt or nickel. This subtle difference can be


Environmental Engineering

FOCUS

strategically exploited. Understanding these

properties, often overlooked in traditional

membrane design, is crucial for creating highly

selective materials capable of distinguishing

between similar ions.

Optimizing Cooperative Ion Transport

Another important consideration in

membrane design is how ions move through

the membrane pores. While ions must bind

selectively to the membrane, there is a delicate

balance between attraction and transport

efficiency. “You need it to be strong enough

for the ion to move into the pore, but if that

interaction is too strong, the ion will become

stuck and won’t permeate through to the other

side,” Violet said. On the other hand, if the

interaction is too weak, the ion may not even

enter the pore.

To tackle this challenge, the researchers

suggested incorporating multiple closely

spaced binding sites within single pores. If

there was only one high-affinity binding site at

the entrance of each pore, the ion could become

stuck and unable to travel through the rest of

the pore, effectively blocking off the opening.

However, if multiple binding sites are arranged

along each pore, the next binding site could

attract the ion and facilitate its movement away

from the initial binding site. This way, the ion

uses the attraction of neighboring binding sites

to navigate through the membrane efficiently.

Another key factor the researchers examined

was pore geometry, particularly the diameter

of the nanopores embedded throughout the

membrane. The pores need to be small enough

to shave off the hydration shell surrounding

the ions, as hydrated ions are larger and

harder to distinguish. However, the channel

length must also be kept short to minimize

the number of binding site interactions, which

can accumulate to slow the transport of ions

through the membrane.

A novel insight from the paper is the

interaction of multiple ions within the

membrane. When many ions are present in

the material, they exert pressure against one

another due to their similar charges.

This repulsion can aid the movement

of ions through the membrane,

accelerating transport. Violet calls

this a “facilitative repulsion,” where

the ions push each other through

the pores, helping each other

overcome the energy barriers that

would otherwise slow their progress.

This cooperative behavior has been

overlooked in traditional membrane science

but could be key to designing more efficient

separation processes. By increasing the

density of binding sites within a membrane,

researchers can increase the number of ions

that enter the material, thereby enhancing the

facilitative effect of these inter-ion interactions.

This could lead to faster ion transport and

improved separation performance, particularly

for applications where large quantities of ions

must be processed quickly.

Pharma-Inspired Computational Screens

To further optimize the design of these

ion separation membranes, the team has

recommended using computational methods

such as molecular dynamics simulations.

These simulations allow researchers to model

the movement of ions through nanopores

and their interactions with functional groups.

By systematically varying factors such as

pore geometry and binding site spacing, the

researchers can predict how different designs

will affect ion selectivity and transport

efficiency. “Using this method, we can

accurately identify an optimal binding energy

or binding site for the membranes,” Violet said.

Drawing inspiration from the pharmaceutical

industry, the team is also testing

machine-learning methods to expedite

the discovery of new functional groups for

membrane materials. In

innovative drug discovery,

high-throughput screening

is used to sift through

thousands of potential

chemical compounds to find

those likely to interact positively with

target receptor sites. Similarly, researchers

can also screen databases to identify potential

chemical components for membrane designs.

“Using the drug discovery model, we can

accurately identify ligands that exhibit the

desired optimal binding energy to target

metal ions,” Violet said. This interdisciplinary

approach could significantly accelerate the

discovery process, facilitating the roll-out of

sustainable resource recovery technologies.

The Future of Resource Recovery

As the global demand for critical metals rises,

developing efficient methods of extraction

from waste streams has become imperative for

a sustainable future. Improvements in methods

for selectively separating cobalt, nickel,

and copper could revolutionize the battery

recycling industry and extend the lifespan of

existing natural resources. Additionally, bioinspired

membranes could be applied to water

treatment to remove heavy metals and other

contaminants from industrial wastewater.

“By leveraging insights from biological ion

channels and employing rational design

principles, we can create novel membrane

materials capable of precise ion separation,

paving the way for a more sustainable and

circular economy,” Elimelech said. ■

ABOUT THE AUTHOR

KENNY CHENG

PHOTOGRAPHY BY JUSTIN BALDASSARRE

Camille Violet, the first author of the paper (left), and

Makenna Parkinson, a first-year PhD student (right),

prepare a membrane to be tested and analyzed.


KENNY CHENG is a sophomore majoring in Molecular, Cellular, and Developmental Biology.

Outside of YSM, Kenny carries out research on lncRNAs in the Breaker Lab and is an editorial

associate for the Yale School of Medicine and the Yale Medicine Magazine.

THE AUTHOR WOULD LIKE TO THANK Camille Violet and Menachem Elimelech for their time

and enthusiasm in sharing their research.

REFERENCES:

Violet, C., Ball, A., Heiranian, M., Villalobos, L. F., Zhang, J., Uralcan, B., Kulik, H., Haji-Akbari,

A., & Elimelech, M. (2024). Designing membranes with specific binding sites for selective ion

separations. Nature Water, 2: 706–718. https://www.doi.org/10.1038/s44221-024-00279-6


FOCUS

Evolution

Deep Dive

How Anglerfish Conquered the

Midnight Zone

By Brandon Quach and Patrick Wahlig

Art by Alondra Moreno Santana


Evolution

FOCUS

In the depths of the midnight zone, where

sunlight fails to penetrate and water

pressure exceeds extremes, anglerfish

have discovered an ocean of rich opportunity.

This species has evolved to thrive over sixteen

thousand feet below sea

level, while exhibiting one

of the highest levels of

species diversity found

in this ecosystem. In a

recent study published

in Current Biology,

researchers in the lab

of Thomas J. Near, a

professor and chair of

the Yale Department

of Ecology and

Evolutionary Biology,

collaborated with the

Dornburg Laboratory

at UNC Charlotte to

investigate the origins

of the anglerfish’s rapid

spread across the ocean

and explore how the

species flourished in such

harsh conditions.

Periods of extreme environmental

change can radically alter ecosystems and

create new ecological opportunities that species

may rapidly exploit. The evolution of new traits

from a common ancestor, allowing species to

adapt to different ecological roles, is known

as adaptive radiation. Over time, adaptive

radiation induces the development of many

new species from a single common ancestor,

forming a single clade. Fifty million years

ago, the common ancestor of the anglerfish

inhabited the ocean floor, also known as the

benthic zone. This ancestor species was wellsuited

to “walk” across the ocean floor on

modified fins. Based on their phylogenetic

data on evolutionary relationships among

species, the researchers hypothesized that this

single ancestor gave rise to over two hundred

species of anglerfish, many of whom now

inhabit the deep open ocean. Anglerfish in the

clade Ceratioidei are no longer confined to the

ocean floor and exhibit a remarkable range of

anatomical and physiological characteristics.

Chase Brownstein (YC ’23), a graduate

student in Yale’s Department of Ecology

and Evolutionary Biology, wanted to use

his evolutionary expertise to understand

the factors driving this incredible example

of species diversification. Examining the

phylogenetic evidence, Brownstein and

his fellow researchers hypothesized that

something external was driving this swift

adaptive radiation: an intense environmental

change might have pushed anglerfish into the

midnight zone and, in the process, inspired a

surprising new mating tactic.

It’s Gettin’ Hot in Here…

Climate change has

impacted our planet for

millions of years. One of

Earth’s most notable climate

change events coincided with the rise

of the anglerfish. “What we’re inferring

about the timing of diversification of

deep-sea lineage is that it corresponds to

global as well as oceanic temperatures,” said

Near, the senior author of the paper.

During the Paleocene-Eocene Thermal

Maximum (PETM), roughly fifty million years

ago, a rapid increase in atmospheric pressures

catalyzed a series of mass extinctions. Although

anglerfish dwelled near the deepest depths

of the ocean, even they weren’t safe from the

incredible impacts of global warming.

The ancestors of the anglerfish were floordwelling

scavengers that had modified, feetlike

fins. However, as water temperatures

increased during the PETM, food became

a scarce resource for all marine life. The

anglerfish thus left the ocean floor, losing their

“feet” in the process. The anglerfishes’ express

trip off the ocean floor prompted a cascade of

adaptation. One could say that the anglerfishes’

ancestors walked so that the modern day fish

could swim.

While the anglerfish had more feeding

opportunities, they now found themselves with

a new problem: reproduction. This led to the

evolution of a unique adaptation—the fusion

of males to females—which we observe

in modern ceratioid anglerfishes.

In this case, temperature

change resulted in

both the adaptation

towards new

habitats and the

development of

new reproductive

modes that had not yet

been seen.

’Til Death Do Us Part

An ancient warming of the oceans may

have propelled the anglerfish into a new

environment, but that’s just the beginning of the

ceratioids’ evolutionary tale. In the isolation of

this dark, new expanse, the only way to secure

a partner for life meant never leaving each

other’s side—literally. Enter sexual parasitism,

a phenomenon that researchers believe was the

catalyst for the rapid expansion of anglerfish

into the midnight zone.

“We think that some form [of sexual

parasitism] actually evolved right at the base,

or right at the common ancestor […] of all

living deep-sea ceratioid anglerfishes,”

Brownstein said. If commitment were

the only factor, Ceratioidei would be

considered one of the best spouses of

all time.

This parasitism can be temporary,

permanent, or a combination of both. In

most cases, the comparatively smaller male

anglerfish will locate a female and attach himself

to her. If this attachment becomes permanent,

the male fuses with the female, integrating

with her body as a sperm-producing organ.

In the harsh conditions of the midnight zone,

sexual parasitism has proven to be an iron-clad

strategy for reproduction, sustaining the clade

Ceratioidei and ensuring an opportunity for

continued survival.

Fishing for Phylogenies

When did anglerfish adopt this reproductive

tactic? Genome sequencing has been a key

part of understanding the evolution of sexual

dimorphism—major physical differences in

sexes—as well as the reproductive modes of

anglerfish. Previous studies relied solely on

mitochondrial DNA or small samples of ten

to twenty common genes, limiting their ability

to trace the

millions of years of evolutionary changes

among anglerfish species. This study took over

1,300 genes from the more comprehensive

modern-day nuclear genome and analyzed

the mutations, achieving a newfound clarity

that far surpasses past techniques.

By searching through these genomes, the



FOCUS

Evolution

A researcher handles an anglerfish sample.

researchers have determined that temporary

attachment was likely the trait of the most

recent common ancestor of all modernday

anglerfishes. This conclusion does not

come without limitations as there are certain

accepted biases in the data and remaining

ambiguities in the evolutionary tree. As a result,

reconstructing the exact timeline of when

key traits evolved can be challenging. “We

cannot do experiments that prove chickens

are dinosaurs. We have to make inferences

by reconstruction from the past,” Near said.

Despite these limitations, the data indicate that

sexual parasitism evolved at the start of the

species’ move into the midnight zone, likely

catalyzing the rapid expansion of ceratioid

anglerfishes that followed. These new insights

offer a clearer understanding of how

anglerfish adapted to survive in such

a harsh, low-density environment

and reveal the evolutionary

pressures that shaped their unique

biology and behaviors.

Knock, Knock, Who’s

There? — Not the Male

In order for sexual

parasitism to work, a complex series of

underlying genetic alterations have to occur.

A key aspect of species survival is the ability

to fend off foreign invaders like viruses and

bacteria that find their way into an organism’s

body. To enable male anglerfish to seamlessly

attach to a female “host,” the adaptive immune

systems of both the male and the female must

be suppressed. Otherwise, each organism

would mount an immune response against

the other. While the stronger individual

might survive, the infeasibility of mating

would ultimately spell

extinction for the species.

The researchers

analyzed previously

sequenced anglerfish

genomes and identified

genes related to the

process of adaptive

immunity, which targets

specific pathogens.

Their temporal analysis

suggested that the

deterioration of these

genes aligned with

the advent of sexual

parasitism in Ceratioidei

species. Sexual parasitism

was the peanut butter,

and the degeneration of adaptive immunity

was the jelly; together, the two allowed for

the reproductive success of anglerfishes in the

midnight zone.

The devolution of adaptive immunity

and the unique form of sexual reproduction

employed by many members of Ceratioidei

might have gotten the fish into the midnight

zone, but that was just one part of their

species diversification. Ceratioidei is an

incredibly diverse clade, exhibiting traits

from spikes to antennae to giant teeth.

The sheer range of incredible adaptations

among these species is shaped by the

unique niches of the deep ocean, with the

advent of sexual parasitism as a vessel for

this journey.

IMAGE COURTESY OF PAUL ALEXANDER-LEJAS

Investigating the Gray Area

Reconstructing genetic histories

is not a flawless science, and different

ABOUT THE

AUTHORS

approaches often lead to different results.

This uncertainty creates “anomaly zones”

in phylogenetic trees—the ecologist’s

rendition of an extended family tree—

where researchers are unable to pinpoint

the proper position of a species among its

relatives. These anomaly zones may create

a little static in the signal, but the general

message of phylogenetic trees can still be

uncovered via careful large-scale analysis. In

this case, the teams’ phylogeny showed that

sexual parasitism evolved in the most recent

common ancestor of modern anglerfish,

likely aiding their adaptation to the deep-sea

environment. This provides further support

for the theory that this unique reproductive

strategy not only addressed the challenges

of mate scarcity but also played a role in the

broader diversification of anglerfish species

across extreme ocean habitats.

Brownstein’s phylogenetic reconstruction

of the anglerfish adaptive radiation serves

as a telling example of environmentallydriven

evolution, and the impact of this

work extends far beyond the midnight zone.

Both Brownstein and Near are particularly

excited about the practical applications of

their recent anglerfish research in relation

to the human adaptive immune system.

Near posits that if similarities exist between

a human’s immune system and that of a

fish, this could lead to great advances in

research targeting organ transplantation,

autoimmune disease, and other areas

involving a misdirected adaptive immune

function. The translational road from

Ceratioidei to humans may not be a simple

one, but Brownstein’s work has provided a

valuable template for future endeavors into

the deep, dark unknown. ■

BRANDON QUACH is a sophomore in Davenport College from Alhambra, California. He currently

conducts research in the Sorrells Lab at the Yale School of Medicine focused on transgenic mosquitoes.

Outside of YSM, Brandon enjoys rearing fish, drinking tea, and trying new restaurants.

PATRICK WAHLIG is a sophomore in Branford College from Falmouth, Maine. He currently conducts

structural biophysical research in the Tang Lab. When he’s not writing, Patrick enjoys fishing, sailing, and

playing broomball.

THE AUTHORS WOULD LIKE TO THANK Chase Brownstein and Dr. Thomas Near for their availability

and willingness to share their research with the public.

FURTHER READING:

BRANDON QUACH

PATRICK WAHLIG

Brownstein, C. D., Zapfe, K. L., Lott, S., Harrington, R. C., Ghezelayagh, A., Dornburg, A., & Near, T. J. (2024).

Synergistic innovations enabled the radiation of anglerfishes in the deep open ocean. Current Biology,

34(11): 2541-2550.e2544. https://www.doi.org/10.1016/j.cub.2024.04.066


Immunology

FOCUS

Inside

Multiple

Sclerosis


The Role of PRDM1-S

in Immune Dysfunction

By Crystal Liu and Risha Chakraborty

Art by Lynn Dai


FOCUS

Immunology

Sometimes, our immune cells stage a

mutiny, turning their defensive weapons

against the body they’re meant to

protect. This betrayal is the defining feature of

autoimmune disorders: the immune system,

which typically protects us from germs and

foreign substances, begins to mistake our

own cells as foreign threats—so it attacks.

One such disorder is multiple sclerosis

(MS). In MS, T cells, a type of immune cell,

misidentify parts of the brain as foreign and

attack their myelin sheaths, an insulating fatty

lining that surrounds neurons. Without these

sheaths, neural signaling slows dramatically,

leading to a wide range of symptoms, from

visual problems and muscle weakness to

urinary dysfunction.

Normally, conventional T cell activity

indicates a robust immune system, but it must

be kept in check to prevent overreaction. This

job falls to a specialized group of T cells called

regulatory T cells (Tregs), which are responsible

for distinguishing between self and non-self

cells and suppressing overactive conventional

T cell responses. While Tregs may not be as

celebrated as their conventional counterparts,

they are crucial players in the immune

system. They were first characterized in

mouse models in 1996 by Shimon Sakaguchi,

a professor at Osaka University, while their

role in humans was described in 2001 by

David Hafler, now the William S. and Lois

Stiles Edgerly Professor of Neurology and

Immunology at the Yale School of Medicine.

In MS, the prevailing hypothesis is that

when Tregs malfunction, T cell activity goes

unchecked, and autoimmunity ensues.

The Hafler Lab has focused on studying

Tregs to better understand the basis of MS. In a

recent study published in Science Translational

Medicine, they examined the mechanism

behind regulatory T cell dysfunction. “We’ve

spent the past quarter century looking at

why [Tregs] are defective, but this paper really

worked out the molecular mechanism for

loss-of-function,” said Hafler, the senior

author of the study.

Identifying A “Master Switch” in MS

The team employed a multi-omics

approach, which integrates multiple types of

biological data, including gene expression and

gene regulation. They isolated regulatory T

cells from MS patients and healthy individuals

as controls, and then performed RNA

sequencing on these cells. RNA sequencing

allows researchers to quantify the expression

of genes in cells of interest, providing insight

into which genes are active. While DNA stores

the genetic information needed for making

proteins, gene expression first involves

transcribing DNA into RNA, which serves

as the template for proteins. Although DNA

sequences are identical across almost all cells

in the body, the expression levels of different

genes within our DNA differ greatly. Since

proteins drive most biochemical reactions

in cells, fluctuations in gene expression levels

can lead to changes in cell function.

“Studies have been focused on how specific

molecules cause Treg dysfunction in MS,

but we’ve never explored unbiased gene

expression profiles from MS patient Tregs,”

PHOTOGRAPHY BY JENNY WONG

Tomokazu Sumida (left), an assistant professor of neurology and the first author of the study, David Hafler (middle), a professor

of neurology and immunology, and Alice Yi (right), a postgraduate research associate, pose together in the Hafler Lab.

said Tomokazu Sumida, an assistant professor

of neurology at Yale School of Medicine and

first author of this study.

When Sumida and colleagues compared

the RNA-sequencing data of MS individuals

to that of the controls, they identified genes

with differing expression levels between

the two groups. One gene was of special

interest: PRDM1.

“When you look at the differential display,

[PRDM1] was one of the highest—it was

strikingly high. And the other factors that

were high were RNAs either induced

or suppressed by PRDM1,” Hafler said.

He explained that PRDM1 encodes B

Lymphocyte-Induced Maturation Protein 1

(BLIMP1), a transcription factor that helps

regulate the transcription of other genes.

PRDM1 expression is increased in MS

patients; it follows that the expression levels

of genes that it up- or down-regulates should

also deviate from controls. For example, ID3,

a gene repressed by BLIMP1, was among the

most significantly under-expressed genes in

MS Tregs.

To confirm that the PRDM1 overexpression

was consistent across different subtypes of

Tregs, the researchers also performed singlecell

RNA sequencing. Their results showed

that PRDM1 was indeed consistently

overexpressed across all Tregs.

Short Form PRDM1: Why Mouse Models

Fall Short

PRDM1 is relatively well-characterized

in mouse models of MS, where its higher

expression is usually linked to less severe

disease. Researchers were therefore surprised

to find PRDM1 was overexpressed in humans

with MS. “We were very confused because

there are very nice studies which showed that

PRDM1 in animal models of MS is associated

with increased Treg function and less disease,”

Hafler said.

Clinical samples were the missing link to

solving this discrepancy between humans

and mice. It turns out that PRDM1 exists in

two forms in humans: the full-length form

(PRDM1-L) and a shorter form, PRDM1-S,

which exists only in dry-nosed mammals, such

as primates and rodents. PRDM1-S encodes a

truncated form of BLIMP1 named BLIMP1-S,

which inhibits the normal function of fulllength

BLIMP1. While this has been studied in

immunology, it was primarily in the context of

cancer, not autoimmunity.


Immunology

FOCUS

The researchers measured PRDM1-S

and PRDM1-L expression in different

immune cells of healthy participants and

found that their proportions varied across

cell types. They went on to characterize

PRDM1 expression in MS patients.

Additional analysis of RNA-sequencing

of Tregs indicated that while PRDM1-S

expression was considerably elevated

in patients with MS, the expression of

PRDM1-L also increased—though not to

a statistically significant degree—which

maintained a constant ratio of short- to

long-form PRDM1. This suggests that the

effects seen in MS are not merely due to a

relative decrease in PRDM1-L activity, as

the relative amounts of both forms remain

unchanged. Still, PRDM1-S upregulation

was correlated with lower expression of

proteins that play an important role in Treg

suppression of conventional T cells. It was

therefore hypothesized that PRDM1-S

must have an independent effect in MS,

separate from its potential interaction

with PRDM1-L.

Armed with this information, the

researchers looked for downstream

pathways that were most affected by

PRDM1-S. A combination of biochemical

and RNA-sequencing analyses revealed

that PRDM1-S overexpression induced the

expression of a gene called SGK1, named

after the protein that it encodes, serum

and glucocorticoid-regulated kinase 1.

This was an interesting finding because the

relationship between PRDM1 and SGK1 has

been previously implicated in numerous

autoimmune diseases, including allergies

and inflammatory bowel disease. The final

linchpin came by identifying the effects of

SGK1 in suppressing the expression and

stabilization of the protein FOXP3, a protein

crucial for Treg function. FOXP3 instability

is a known factor in Treg dysfunction in MS.

Putting the pieces together for this

pathway explained some patient data

that had long puzzled physicians. MS

treatments have included low-salt

diets, based on the observation that

salt exacerbates autoimmune flare-ups.

Now, researchers know that a highsalt

environment leads to increased

PRDM1-S expression. Understanding

that the PRDM1-S/SGK1 pathway drives

MS patient symptoms underscores the

importance of studying this pathway for

the development of future therapeutics.


Transcription Factors for the

Transcription Factor?

The researchers also sought to

understand the upstream causes of

PRDM1-S upregulation in Tregs, such

as whether certain transcription factors

regulate PRDM1-S and PRDM1-L differently.

They performed an assay to find regions of

DNA that are more loosely packed, which

corresponds to increased accessibility for

transcription factor binding and therefore

increased rates of transcription. In the case of

PRDM1, overall accessibility was comparable

between MS patients and controls.

Using this data, it is also possible to

identify the binding sites, also known

as “footprints,” of specific factors. This

analysis reveals the extent of transcription

factor interaction with a DNA sequence

based on its chemistry rather than how

tightly the DNA is packed. Here, the

researchers found increased binding of

activating protein-1 (AP-1) and interferon

regulatory factor (IRF) transcription factor

families in MS patients. These factors have

previously been associated with immune

cell differentiation that gives rise to Tregs.

The team inhibited the expression of BATF

and IRF4 transcription factors, members

of the AP-1 and IRF families, respectively,

and found that knockdown of either

transcription factor led to higher PRDM1-S

expression. Thus, losing these two key Treg

regulators seems to be a potential cause for

aberrant PRDM1-S induction in MS.

ABOUT THE

AUTHORS

Broad Implications and Future Directions

“I think PRDM1-S is a highly overlooked

transcription factor in humans,” Sumida said.

Different immune cell types show distinct

expression patterns of the short and long

forms of PRDM1. For example, B cells, which

produce antibodies in adaptive immune

response, are tightly regulated to express only

PRDM1-L, and upregulation of PRDM1-S

is associated with B cell lymphoma. On the

other hand, in natural killer cells, PRDM1-S

expression is much higher than PRDM1-L

expression. The Sidi Chen Lab at Yale recently

reported that a CRISPR-generated shortened

version of PRDM1 led to higher CAR-T

(chimeric antigen receptor T-cell therapy)

efficacy in cancers.

Given the substantial implications of

PRDM1-S, the Hafler and Sumida Labs

plan to continue their research on this

transcription factor. “We’re working with

some structural biologists in crystallography

to come up with small molecules that

block short-form PRDM1,” Hafler said.

Since the transcription factor is involved in

many cellular pathways and autoimmune

disorders, they hope that it will be a

particularly lucrative molecular target for

drug development. Eventually, Hafler is

interested in targeting SGK as well. As the

team works on elucidating the effects of

PRDM1-S and its downstream effects,

their findings may pave the way for

novel treatments for MS and other

autoimmune disorders. ■

CRYSTAL LIU

RISHA CHAKRABORTY

CRYSTAL LIU is a junior in Pierson College majoring in MCDB. Besides writing for YSM, she conducts

molecular biochemistry research on the HPV L2 protein at the DiMaio Lab and manages backstage

and administrative duties at Yale Vermilion Theater.

RISHA CHAKRABORTY is a senior 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.

THE AUTHOR WOULD LIKE TO THANK David Hafler and Tomokazu Sumida for their time and

enthusiasm in sharing their work.

FURTHER READING

Sumida, T. S., Lincoln, M. R., He, L., Park, Y., Ota, M., Oguchi, A., Son, R., Yi, A., Stillwell, H. A., Leissa,

G. A., Fujio, K., Murakawa, Y., Kulminski, A. M., Epstein, C. B., Bernstein, B. E., Kellis, M., & Hafler, D. A.

(2024). An autoimmune transcriptional circuit drives FOXP3 + regulatory T cell dysfunction. Science

Translational Medicine, 16(762): eadp1720. https://doi.org/10.1126/scitranslmed.adp1720


FOCUS

Physics

Upping the Anti

Meet the Heaviest Anti-Nucleus

By Max Watzky

Art by Luna Aguilar


Physics

FOCUS

Blink, and you’ll miss it—scientists

at the STAR Collaboration, an

international effort, are smashing

metal ions together at nearly the speed of

light, unleashing an unfathomable amount

of energy with each impact. For a brief

fraction of a second, the colliding atoms are

broken down not merely into protons and

neutrons, but into an even more primordial

form: quarks and gluons, the basic building

blocks of all matter. The resulting soup

of particles is so hot and dense that it is

thought to resemble conditions in the early

universe, just a few microseconds after the

Big Bang. As the ball of quark-gluon plasma

expands, spreading out at a dizzying clip,

it rapidly cools and settles into larger and

more complex structures. By studying what

emerges from their Big-Bang-in-a-jar, the

researchers seek to probe not only the nature

of matter and the laws of physics, but also

the underlying logic of the universe itself.

The key to this exploration lies in one

particular kind of object: antimatter. In

August of 2024, the STAR team announced

that they had detected the largest group,

or nucleus, of antiparticles ever found.

Their work, the culmination of decades of

effort, pushes the boundaries of particle

physics and sheds light on the fundamental

axioms that govern our world. STAR is one

of the largest and longest-running physics

collaborations in the world: since its

inception in 1991, thousands of scientists

from across the globe have worked together

on the project.

One of STAR’s most essential researchers

is Helen Caines, the Horace D. Taft Professor

of Physics at Yale. Caines chaired the STAR

Collaboration as its spokeswoman from 2017

to 2023 and studies the quark-gluon plasma

by examining the particles it creates. Working

alongside Caines is fellow STAR researcher

Fernando Flor, a postdoctoral fellow at Yale

who develops computational models to

help interpret the high-energy collision data

generated by their particle accelerator.

One Particle, Two Charges

But hold on a second—what even is

antimatter? Though the word is often bandied

about by science fiction writers and futurists,

few people understand what it really means.

The concept of antimatter was first

proposed over a century ago by the

mathematical physicist Paul Dirac. In 1929,

Dirac was interested in combining the new

theories of quantum mechanics and special

relativity, which both offered insights into

the nature of matter and energy. He began

by working on a seemingly simple case study,

the electron. But just as the square root of a

number can yield both a positive and negative

answer, Dirac’s equations predicted that

the electron can possess either a negative or

positive charge. Electrons were universally

known to be negatively charged particles; the

notion of a positively charged counterpart—

later named the anti-electron, or “positron”—

was nonsensical. The scientific community

twisted itself into knots trying to disprove

the finding. Yet, only three years later, Dirac

was vindicated. The existence of the positron

was confirmed, unlocking a whole new world

of antiparticles: objects that share the same

properties as their ordinary counterparts,

but have opposite charges. For objects that

lack charge, like neutrons, their antiparticle

equivalents have other properties reversed,

such as their quantum number, which

describes the particle’s possible energy states.

Dirac’s work quickly revealed a deeper

problem. The universe had started with a

net charge of zero, so there should have been

equal amounts of positively and negatively

charged objects, elementary particles and

antiparticles. “We should see an equal

number of quarks and antiquarks come

out of this process, because the quantum

numbers and charge have to be conserved.

For every charge you should make an anticharge,

and for every quark you should

make an antiquark,” Caines said.

Yet, when we look out into the universe

PHOTO COURTESY OF BROOKHAVEN NATIONAL LABORATORY COMMUNICATED BY WILL ARCHACKI

The quark-gluon plasma detector of the Solenoidal Tracker at the relativistic heavy ion collider (RHIC), a part of Brookhaven

National Laboratory.

today, there is almost no antimatter. The

proof? When matter and antimatter interact,

they destroy one another, converting into pure

energy in a process known as annihilation.

This process is extremely violent: if just one

gram of matter came in contact with one

gram of antimatter, the resulting explosion

would release enough energy to destroy a

city. If there were any significant amounts

of antimatter in our environment, we’d be

in serious trouble. At some point between

the beginning of the universe and now,

something must have wiped out most of the

antimatter—without touching regular matter

in the process.

Why Antimatter Matters

This asymmetry between matter and

antimatter has puzzled physicists for decades

as they sought to understand how the

properties of antimatter might differ from

those of ordinary matter. One theory suggests

that antiparticles might not bond in the same

way as ordinary matter and are therefore left

in smaller, higher-energy forms that are more

vulnerable to decay.

“Is this the reason we’re in our matter

universe—because, for some reason, antimatter

simply cannot form?” Caines said. “Perhaps we

can make antiprotons and positrons, but they

just don’t combine into nuclei in the same way.”

But if this was true, it would challenge one

of the most fundamental axioms of modern

physics, an idea called charge, parity, and time

reversal (CPT) symmetry. Much like how a

sphere appears the same from every angle, CPT

symmetry asserts that particles should look the



FOCUS

Physics

same

if you swap their

charge, direction of

motion, and orientation in time.

This implies that particles and

their corresponding antiparticles are

fundamentally identical, just moving in

opposite directions. Therefore, they should

be governed by the same physical laws, and

should bond in the same way. Thus, the study

of antiparticle bonding has the potential to

confirm or undermine CPT symmetry, one of

our most essential notions about the nature of

reality itself.

At first, antimatter researchers looked to

space for their investigations. “Originally,

we were limited to studying extraterrestrial

sources of antiparticles, like cosmic rays

or particles from the Sun,” Flor said. Since

these particles spend their lives in a nearperfect

vacuum, they never have a chance to

be annihilated, and occasionally make it to

Earth’s surface unscathed, where they can be

detected. But such events are rare—in order

to observe an antimatter bonding event, two

cosmic rays would have to collide, a nearly

impossible event. So, in order to investigate

antimatter bonding, it’s become more feasible

for us to first create the antiparticles ourselves.

The Antimatter Hypernucleus Is Born

This is where STAR, which stands for

the Solenoidal Tracker at RHIC, comes in.

STAR is based at the relativistic heavy ion

collider (RHIC), a particle accelerator at

Brookhaven National Laboratory. There,

scientists accelerate gold, uranium, zirconium,

and ruthenium to 99.996 percent the speed

of light—fast enough to traverse the fourkilometer

circumference of the device over

seventy-five thousand times per second.

When two of these massive atoms collide,

they are heated to over seven trillion degrees

Fahrenheit, scrambling their constituent

particles into quark-gluon plasma. Out of this

quark-gluon plasma emerges antiparticles,

which can then bond to form nuclei.

However, some nuclei—including the

newly discovered nucleus—decay very

quickly, making them challenging to

detect. These are called “hypernuclei”

because they contain an extra

particle: an unstable twin of the

proton called a lambda hyperon.

Hypernuclei provide another critical

avenue to explore antimatter bonding,

and ultimately probe CPT symmetry. “The

question becomes: can you bind a lambda

particle with an antiproton and an antineutron

in the same way that you can bind their matter

equivalents?” Caines said.

Because the lambda hyperon is unstable,

it causes its parent nuclei to decay rapidly,

splitting up into smaller particles after just a

fraction of a second. Therefore, STAR looks

not for the hypernuclei themselves but for their

byproducts. The detector at STAR is effectively

an enormous container filled with gas. As the

byproduct particles zip through the gaseous

medium, they ionize it, releasing electrons.

The new electrons are exposed to electric

and magnetic fields, causing them to move in

different directions. “If we can measure [the

electrons’] location and drift velocity at the

detector, we can figure out what position they

came from in the detector,” Caines said. By

tracing the byproducts in this way, STAR can

determine where and what they came from.

The new antimatter hypernucleus consists

of a lambda hyperon, an antiproton, and two

antineutrons: the most massive antimatter

configuration ever discovered. However, its

complexity means that it forms extremely

rarely. In order to detect the new antimatter

hypernucleus, the STAR team had to register

over seven billion collisions. Out of this sample,

the team is only confident that they saw the

new nucleus fifteen or sixteen times. “For

context, this would be like going around the

ABOUT THE AUTHOR

PHOTO COURTESY OF BROOKHAVEN NATIONAL LABORATORY

A group of visiting students tours the Brookhaven National

Laboratory facilities.

planet, polling everyone that exists, and asking

if a dozen or two of them have something in

common,” Flor said.

The discovery of this new hypernuclei

suggests that CPT symmetry works—for now.

The STAR team combed through all seven

billion collisions, searching for clues about the

properties of their new hypernucleus. They

found that it forms and decays at the same rate

as its matter equivalent, confirming that they

both obey the same laws of physics.

Conclusions and Future Possibilities

The STAR scientists are exhilarated. The

creation of the new hypernucleus opens

the door to new possibilities, like exploring

the inner structure of antimatter atoms.

“Going forward, we’re very interested to

see if the proton, neutron and lambda in

this nucleus are arranged in a different

way from how we’d expect,” Caines said.

As STAR approaches its technical limits,

new experiments are on the horizon.

Brookhaven is currently constructing

a new electron-ion collider, which will

help scientists probe the inner structure

of atoms with unprecedented detail.

“We’re moving into a new and exciting

space, limited only by math and our own

imagination,” Flor said. ■

MAX WATZKY

MAX WATZKY is a sophomore in Benjamin Franklin College studying physics and applied mathematics.

Outside of YSM, he serves as Prize Lecture Chair for the Society of Physics Students, plays trombone in

the Yale Concert Band, and extends his four-hundred-day streak on Duolingo.

THE AUTHOR WOULD LIKE TO OFFER HIS THANKS to Dr. Helen Caines and Dr. Fernando Flor for

their time, warmth, and expertise.

FURTHER READING:

STAR Collaboration (2024). Observation of the antimatter hypernucleus Λ 4 H. Nature, 632: 1026–1031.

https://doi.org/10.1038/s41586-024-07823-0


Geology

FEATURE

LIQUID ASSETS

REIMAGINING THE ORIGINS

OF WATER ON EARTH

BY MAKENA SENZON

ART BY NINA LIU

In 1990, NASA’s Voyager 1 spacecraft captured a vast image

of local space. Against the cosmos is a speck—a faint blue

group of pixels, affectionately known as “The Pale Blue

Dot,” or more simply, Earth. Earth is characterized not just by

its location in the solar system but also for the life-sustaining

substance that gives it its distinctive, pale blue color: water. But

when this water originated on the planet is a mystery.

In newly published research, geologists have added a prequel to

our understanding of water’s history. Hamed Gamaleldien,

along with a team of fellow scientists from Curtin University

in Australia, uncovered evidence that freshwater arose on Earth

four billion years ago—five hundred million years earlier than

previously thought. This means that life could have emerged on

Earth earlier than expected.

Gamaleldien described the satisfaction he finds in this new

discovery. “To start from looking at my own life and then push

the start of all life back by five hundred million years—it’s so

exciting,” Gamaleldien said. The sign for when freshwater first

emerged came from ancient rocks in the Jack Hills in Western

Australia. When Gamaleldien was a PhD student, the chair

of his thesis panel, Simon A. Wilde, led him to the Jack Hills

to solve the mystery of the origin of ancient water. Wilde had

been excavating samples of the mineral zircon in that region

since 1983.

“There was a very unsuccessful first year,” Wilde said. “But

in 1984, we sort of hit the jackpot, and that’s when we found

what was then the oldest crystal on Earth.” They found zircon.

Zircon is one of the gold standards in geochemistry research,

both because it contains uranium utilized for specific dating

and because it remains stable throughout time. One crystal

of zircon can resist change across eons of metamorphisms

and weathering.

In the new research, Gamaleldien and the team analyzed the

oxygen isotopes in zircon crystals that they established to be up to

four billion years old. Oxygen has two major isotopes, and when

comparing the prevalence of each, scientists can observe distinct

ratios arising from freshwater

and saltwater environments.

Based on around fifteen hundred

isotope analyses and statistical

simulations, it was found that these

zircon crystals were exposed to a

mixture of salt and freshwater four

billion years ago.

As anyone’s daily water usage

can attest, water is connected to


a much larger story of our planet and life itself. Freshwater cycles

through the atmosphere and percolates through the ground in

the hydrological cycle, a process necessary for the origin of

life. Based on the information from the oxygen isotopes, the

researchers concluded that the hydrological cycle began at

least four billion years ago. That idea is still controversial to

some scientists, as it would shift the timeline for the origin

of life to less than six hundred million after Earth formed, a

relatively short period in geological time. The oxygen isotope

ratios that correlate with salt and freshwater are based on modern

data, so it is impossible to guarantee that these ratios have been

constant throughout time. Still, the team hopes their research

will reveal insights into the origin of life on Earth.

“Do we have evidence that life started four billion years [before]

now?” Gamaleldien said. “We don’t know. But we [had] the

recipe. We [had] the ingredients and the main recipes to form

life, which is dry land and freshwater, and this was the main

implication of our discovery.”

Another recent research paper out of the Institute of Geophysics

at Polish Academy of Sciences found similar findings by analyzing

oxygen isotopes from Antarctic rocks. The paper’s authors

dated the emergence of freshwater to at least 3.7 billion

years ago. Though the date is later than Gamaleldien’s work

suggested, it still substantiates that freshwater may have been

on the planet earlier than the previously theorized date of 3.5

billion years ago.

Now, with the potential for life five hundred million years

earlier than previously thought, Gamaleldien, who has moved

to Khalifa University in the United Arab Emirates, hopes to shift

his focus to finding proof of life through RNA chemical traces

from rocks. “We should push scientists and

astrobiologists to start to search for

new life,” Gamaleldien said. ■


FEATURE

Computer Science

IMAGE COURTESY OF ZHIXUAN LIU

In these AI-generated images, the new SCoFT technique was used to alter the initial Stable Diffusion

images to create culturally relevant responses to the prompt “Two people wearing traditional

clothing, in [Culture].”

When you’re visiting a country you’ve never been to

before, you might rely on a travel guide to navigate

the streets, find the best food, and understand the

local customs. But what if that guide was written based on

outdated or incorrect stereotypes, leading you to misunderstand

traditions, behaviors, and beliefs? This is similar to what happens

when generative artificial intelligence (AI) creates images of

different cultures. Like the travel guide, AI models rely on vast

amounts of data to create depictions of the world. And crucially,

if that data is biased, the results can be deeply flawed. Instead

of accurate depictions, AI-generated images can reinforce

outdated, oversimplified, or entirely incorrect stereotypes about

cultures, perpetuating a distorted view of the world. Just as a

bad guidebook can mislead a traveler, these images can mislead

viewers, reinforcing biases rather than breaking them down.

New text-to-image generative AI models like Stable Diffusion

enable users to transform text descriptions into custom images—

and they can produce some truly impressive visuals. These AI

models are created through an extensive training process where

they learn through trial and error, making random guesses on

a dataset where humans have provided images with text labels.

Stable Diffusion was trained on more than 5.85 billion textto-image-pairs

in the Large-scale Artificial Intelligence Open

Network (LAION) dataset. However, there are problems with

this approach. Prompting Stable Diffusion to generate an image

of a modern street in a non-Western city may create something

that reflects stereotypes from the West rather than an accurate

depiction. “The results were not satisfying,” said Zhixuan Liu, a

researcher at the Robotics Institute at Carnegie Mellon University

who observed these troubling images.

Liu and a team of fellow researchers focused on enhancing

generative AI to promote more inclusive representations. The

team itself reflected diversity: Liu is Chinese, her advisor is

Korean, and one of her closest colleagues is Nigerian. Together,

they frequently tested Stable Diffusion and other AI models to

assess their accuracy in reflecting their own respective cultures.

“[The images] are not even Chinese. They’re not Korean. They’re

not Nigerian. They all have Westernized cultural bias,” Liu said.

Responding to these cultural misrepresentations, the team began

working on their solution in November 2022, only months after

the release of Stable Diffusion.

INCLUSIVE

IMAGES

SQUISHING THE BIAS BUG IN AI

BY BRANDON NGO

ART BY MALINA REBER

Liu aimed to tackle a major issue: the massive, flawed datasets

like LAION that contributed to the harmful cultural stereotypes

produced by the AI models. These datasets are typically sourced

from the web, where minority cultures are often underrepresented,

leading to biased outputs that fail to accurately reflect cultural

diversity. “The distribution of these datasets is not good. You may

find many authentic Chinese, Vietnamese, or Korean images, but

the portion is very small in comparison to Western adaptations,”

Liu said. To address this issue, Liu’s research team developed a

new dataset called the Cross-Cultural Understanding Benchmark

(CCUB), designed to provide more accurate representations

of these underrepresented cultures. This dataset was created

through direct engagement with the communities it represented,

ensuring that their cultural nuances were better captured and

reflected in the data. “This data set is very small but accurate. It

contains several cultures, and for each culture, we recruit people

from that culture to help us collect the text and image data from

their respective cultures,” Liu said.

After developing the CCUB dataset, Liu’s research team created

a new image-modifying technique called Self-Contrastive Fine-

Tuning (SCoFT) for text-to-image AI models. This method

adjusts certain settings in models like Stable Diffusion, allowing it

to adapt from generating typical images to creating ones that are

more culturally relevant. The team then applied SCoFT to their

curated dataset, which helped the model produce images that

better reflect different cultural contexts. Overall, this approach

improved the AI’s ability to generate culturally accurate images

based on descriptions.

Improving the cultural accuracy of generative AI models like

Stable Diffusion is essential because the images they generate

have profound impacts on how cultures are represented to global

audiences. In the future, Liu hopes that generative AI models will

use the CCUB dataset to produce images that more accurately

represent marginalized cultures. This effort aims to reduce bias and

improve the inclusivity of AI-generated media. “The development

of the CCUB dataset is just the beginning. We continue to contact

more people from these marginalized cultures to expand our

dataset,” Liu said. With each improvement to these models, we

move closer to a more inclusive and accurate portrayal of diverse

cultures, emphasizing the importance of ongoing innovation and

collaboration across cultures to address these biases. ■


FEATURE

THE LOTUS EFFECT

PLANTS INSPIRE NEXT-GEN CANCER

RESEARCH TECH

BY MICHAEL SARULLO

ART BY MANDY CHEN

Biomedical Engineering

When a flourishing garden is overrun with a variety

of weeds, each festering in different soil types and

conditions, it becomes difficult to eradicate these

invasive species. This chaotic scene mirrors the challenges

researchers face in studying cancer metastasis, where clusters

of cancer cells travel through the bloodstream, often leading to

devastating consequences. Just as some weeds develop resistance

to herbicides, metastatic tumors exhibit diverse genetic traits

that help them evade standard treatments, complicating efforts

to manage their spread. For decades, scientists have struggled

to replicate the chaotic 3D structure of these cell clusters in the

lab, limiting opportunities in metastasis research. Fortunately, a

breakthrough is on the horizon, driven by innovative research that

draws inspiration from nature.

Many cancers follow a common maturation process: they

first begin in a localized area of the body; then, in later stages,

parts of the growing tumor, called metastases, break off,

spreading throughout the bloodstream to the rest of the body

in a process known as metastasis. In most cancers, once these

metastases spread, survival rates become grim. Until now, a

realistic, accurate representation of the disorderly 3D structure

of tumor cells has yet to be efficiently produced and replicated

in laboratories.

Typically, analysis of tumor cells in the lab starts with

growing cells in 2D sheets—a good enough solution for many

applications. However, for studies of metastases in the blood,

sheets misrepresent reality. “A 2D sheet of cells does not

accurately represent the non-uniform and uneven stacking of

cells against one another as what occurs in real-life metastases,”

said Michael King, a professor of bioengineering at Rice

University. Because the current methods of mimicking these

realistic 3D tumors are neither efficient nor cost-effective,

much research focused on the behavior of metastases has been

restricted. However, a new project within King’s lab headed

by graduate student Maria Lopez-Cavestany may have broken

this barrier.

In a new study funded by the National Institutes of Health

(NIH grant number: CA203991), Lopez-Cavestany used a

biomimetic approach:

u t i l i z i n g

n a t u r a l

phenomena

to engineer

biological

replicas

f o r

human disease (in this case, tumor formation). Coined the

superhydrophobic array device (SHArD), Lopez-Cavestany’s

cell-growth device executes what is commonly known as the

“Lotus Effect”—a crown jewel in the field of bioengineering.

Think about the lotus flower: water droplets bead and fall off

its waxy surface. SHArD utilizes this “Lotus Effect” by growing

tumor cells in small wells on a superhydrophobic zinc oxide-

coated wafer, causing the cells to cluster into a 3D structure.

Using the water-shedding property of SHArD, Lopez-Cavestany

was able to simulate the unorganized 3D structure of a tumor in

a process so straightforward that it could be employed for a low

cost by any lab with step-by-step instructions.

The motivation for the project was clear: “[A 3D solution]

takes more time and costs more, so for high-throughput drug

testing, you usually want something that’s cheap and easy to use

to get fast results. But we believe that adding 3D models into

mainstream research, maybe after the initial 2D testing, could

give more reliable results that better predict how clinical trials

will turn out,” Lopez-Cavestany said. Integrating efficient 3D

models into mainstream research, as Lopez-Cavestany suggests,

could prove essential for testing candidate therapeutics to

understand the behavior of cancer cells as they bunch up into

clumps within the blood.

The road to discovery was not without its challenges. “We

used photolithography, which typically handles thinner layers,

but we needed three hundred-micron structures,” Lopez-

Cavestany said. “The main issue was adhesion; if the resin

cooled too quickly after baking, it could snap off the wafer.”

However, thanks to collaboration with Vanderbilt University

and the Oak Ridge National Laboratories, Lopez-Cavestany

developed a protocol using thin grids of resin under a thicker

layer to achieve proper adhesion. Such a protocol has allowed

SHArD to retain its efficient and replicable nature, critical for

future usage in metastasis research.

King is understandably optimistic about this work. “Our goal

is to understand how cancer cells survive in the bloodstream

long enough to form metastases. If we can prevent that, most

cancers could become more treatable and survivable. The

experiments in Maria’s paper are a significant step toward

advancing that research,” King said.

With this work done, Lopez-Cavestany is continuing her

research at Cambridge University, and she plans to become

a professor. King and Lopez-Cavestany emphasized their

excitement for the next generation of researchers based on their

positive experience with this work. If research is a true passion,

then go for it, they suggest. Many surprises lie in store. ■



FEATURE

Neuroscience

HUE'S THE THING...

Early Experiences With Limited Color

Help the Brain Learn to See

BY ANNLI ZHU AND DERECK KA-HON TRAN

ART BY MELODY JIANG

Color is a crucial part of how most

people perceive the world. Even

still, most people have little trouble

recognizing an image that has its colors

modified—after all, most people have no

difficulty recognizing objects or people in

a black-and-white film. New research may

indicate, however, that without a specific

developmental trajectory, some people

may end up relying too heavily on color.

Investigations into the experiences of

blind people who gained their sight later

in life through a program called Project

Prakash, along with simulations of

complex computer learning models, may

indicate more about the exact timeline of

development for color vision in humans.

Project Prakash was launched in 2005

by Pawan Sinha in India, where there

is an outsize population of people with

untreated cataracts. The project sought to

restore vision to children in India born

with cataracts in both eyes—a form of

blindness. While the noble cause didn’t

begin with the purpose of learning more

about our vision developmental timelines,

MIT postdoctoral researchers

Marin and Lukas

Vogelsang, alongside

Project Prakash research

scientist Priti Gupta, saw

an opportunity to do

just that.

“I would say the research

question that really drove the

study—so really the motivation,

the motivating piece—is quite

simple, which is ‘how come you

and I, and all of us, are so good

at recognizing objects or

also faces in these old, say,

black-and-white movies

or photographs?’” Lukas

Vogelsang said. “Because

in our daily lives we see all

these colors, and they’re so

vivid and they seem so

important, but if you

remove them, we’re

still quite good

at pretty much

e ver y t h i ng…We

seem to be so good at this, but

it’s not so clear as to why.”

With that question floating around

Gupta’s and the Vogelsangs’ minds,

they began to study the rather unique

population of children from Project

Prakash. In exploring the cases of Project

Prakash, the researchers discovered

something quite remarkable: although the

children in question were living without

sight for a long period of time, their visual

processing abilities were able to recover

and adapt to our world quite quickly, save

for a few key aspects.

In one revealing experiment, groups

of children were first shown images of

everyday objects, like a banana or a tree,

in full color as well as in grayscale. For the

born-sighted child, there was almost no

difference in recognition success between

the color images and the grayscale images.

Demonstrating the human body’s ability

to quickly adapt, the late-sighted

children didn’t actually have much

problem readjusting to chromatic

vision and performed quite

well at recognizing the color

images. However, the same

could not be said for the

grayscale images.

“As we would expect,

the normally sighted

controls, like you or me,

have almost no difference

in [chromatic versus

grayscale] recognition. But

what we did find—and

this is a bit interesting—

is that these late-sighted

children…they do have a

strong difference,” Vogelsang said. “So for

them, when color information is removed,

their recognition is actually quite poor.”

Evidently, there’s something peculiar

about how these late-sighted children

develop vision. For most newborns,

the eye’s retina and cortex are not fully

developed at birth, meaning that the

color information the brain receives is

quite limited. As such, the brain learns

to distinguish visual information based

on shape, luminance, and other features.

When the eyes improve later in infancy,

color information becomes incorporated

into the mix. However, this is not the case

for late-sighted individuals, whose color

information is incorporated far earlier.

As such, the researchers hypothesized,

this overreliance on color to distinguish

images may hinder visual development.

“These limitations of normal

development may be, if you will, a feature,

not a bug,” Vogelsang said.

To test this hypothesis, the research team

simulated the development of the human

visual system using AlexNet, a wellknown

convolutional neural network (a

computational model of the brain capable

of learning). This allowed them to reliably

and ethically carry out experiments

without harming the development of real

children. “These networks are by no means


Neuroscience

FEATURE

perfect models of the biological system,”

Vogelsang said. “But they still serve an

important purpose.”

Two different instances of AlexNet were

trained on different sets of images. In

the first training approach, researchers

started by only feeding the neural network

grayscale images, and later introduced

color images (gray to color, or G2C). This

mimicked the way human vision most

often develops, where infants initially see

in limited color and gradually experience

full color as their vision matures in

the first few years of life. In the second

approach, the neural network was trained

on colored images only from the very

beginning (C2C). This modeled the visual

development of the Prakash children.

The researchers discovered that

the model simulating born-sighted

development could successfully identify

objects in both grayscale and color images,

and it remained robust against other color

changes. In contrast, the model trained

only on color images, like the Project

Prakash children, still did well on fullcolor

images but struggled to generalize

well to grayscale or hue-altered images,

highlighting the importance of early

exposure to diverse visual inputs.

In addition to seeing training data in

grayscale at all, it also mattered when

that data was seen. When the researchers

swapped the order of visual input, training

the model first on colored images then

grayscale ones (C2G), the model became

very good at identifying grayscale images,

but lost its ability to identify color well.

When the researchers analyzed the inner

workings of their G2C model, they found

that it was relying on luminance to identify

objects. When color input was introduced,

this fundamental approach did not change,

since the same strategy worked just as well.

On the other hand, when the C2G model

was introduced to grayscale images later

in its training process, it could not adapt

its strategy well enough to identify both

full-color and colorless images accurately,

instead becoming confused.

The combination of these two findings

confirmed the research team’s suspicions.

Limited visual input during infancy is

crucial to visual development, and this

limitation has to happen at the very

beginning of the visual development

process in order to be effective.

The research team also believes that

their findings could be generalized to

other sensory systems in humans. It is

well known that brain plasticity is higher

during infancy, meaning that it learns

faster and adapts more easily. Therefore,

training on limited input—whether that

be color, auditory queues, or something

else—earlier in life may in fact be beneficial

to development. In previous studies, the

team had investigated visual acuity using

a similar approach and found that infants

with more precise vision earlier tended to

focus on small details and had a harder

time seeing the larger shapes and contours

IMAGE COURTESY OF ICECLANL

A close-up depicts a congenital cataract in the human eye.

of a scene. “So this theory we have—of early

limitations being a good thing—might be

quite a broad one,” Vogelsang said.

Vogelsang hopes that these results could

also help guide the rehabilitation process

of children who gain vision later in life. By

somehow artificially limiting their color

perception immediately after recovering

vision, the same developmental arc could

potentially happen, leading to a more

normal visual perception system.

“This would really be closing the full

loop,” Vogelsang said “If we learned

something about normal development

from these children, and then could

improve the outcomes for these children

using what we learned…that would be the

ultimate dream.” ■



FEATURE

Ecology

PLEASE BEEHAVE!

CRACKING THE CODE OF

TARGETED POLLINATION

BY JORDAN THOMAS

ART BY PATRICIA JOSEPH

While it may not be easy to

teach bees to perform aerial

acrobatics like in Cirque du

Soleil shows, training bees to pollinate

certain crops to improve agricultural

yield has become a promising reality—

so much so that it may be the solution

to the growing threats facing our highly

pollinator-dependent agricultural system.

Pollination is an invaluable service

bees and a number of other pollinators

provide to the Earth’s ecosystems.

Approximately three-fourths of

the Earth’s flora and one-third of

agricultural crops, depending on the

source, are pollination-dependent.

This means just about every meal you

eat is made possible in some form by

pollinators. If they don’t pollinate crops,

those crops generally can’t grow. To

address the high demand for pollination

in steadily expanding agricultural

settings, considerable effort has been

focused on harnessing pollinators and

guiding them to specific crops. While

some plans to direct pollinators have

been more successful than others, one

method in particular has generated a lot

of buzz.

“The idea is that conditioning is a very

useful procedure. And so, with this in

mind, we asked the following question:

Is it possible to train social individuals

to a specific target crop?” said Walter

M. Farina, a professor and insect

physiology researcher at the University

of Buenos Aires. “Under lab conditions

we’ve obtained a really clear cause-andeffect

relationship between training bee

hives and bee foraging at specific

flora. This will have

positive outcomes for

crop pollination and

crop yield.”

Such an approach

to increase agricultural

crop pollination

through

“c o n d i t i o n i n g ”

bees is referred to

as a targeted pollination

strategy.

This method aims

to increase the

pollination of

particular crops

by teaching bees

to respond to

certain stimuli

like aromas

that emanate

from the target

crop naturally. In

a study Farina conducted on bees, he

and researchers in his lab conditioned

honey bees by exploiting their sense of

smell, or olfactory discrimination. They

did so by pairing a sugar-filled liquid

with a synthetically produced scent

that mimicked the natural aroma of a

particular plant. By creating this aromareward

pairing, bees were taught to

target specified plants, such as almonds

and apples. Previously, this aromareward

conditioning strategy had only

been applied to flora and agricultural

crops that produce nectar, which is a

natural food source many pollinators

find delicious. Whether the targeted

pollination strategy would hold for flora

and crops without the natural reward of

nectar was the next question Farina and

his group would have to answer.

“The new challenge for us was how

to approach other crops, because

many of them contain no nectar. For

instance, the kiwi fruit crop is not a

huge temptation for honey bee colonies

because they are nectarless flowers and

do not offer an immediate reward for

pollinators,” Farina said.

Farina’s group recently published

their findings on this topic. In their

study, they detailed how utilizing

olfactory-conditioned bees to target

nectarless crops may be just as feasible

as conditioning bees to target nectarproducing

flora. The researchers chose

kiwi flowers as their nectarless target

crop and produced six mimic odors of

varying content to simulate the kiwi’s

natural odor. Six groups of honey bees

were initially conditioned over five

trials with sugar-containing liquid

scented with one of the six mimic odors.

“This absolute conditioning phase of the


Ecology

FEATURE

honey bees showed the potential of the

mimic odors. If the mimic odor that

we develop is really good, the bees not

only learn during the conditioning

phase, but also remember or, we say,

generalize,” Farina said. “When we

offer the natural fragrances of the male

and female flower, the proportion the

bees respond to is based on the quality

of the mimic odor. From this, we find

the best candidate for us to continue

conditioning the bees.”

For the group of bees initially

conditioned with the synthetic mimic

odor named kiwifruit mimic odor

(KM), over ninety percent of bees

extended their straw-like mouth, called

the proboscis, when subsequently

presented with the sugarless, natural

kiwi-scented liquid. This indicated the

similarity between KM and the natural

aroma of kiwi flowers. Now that part

A of the research was completed, the


IMAGE COURTESY OF PIXNIO

Bees forage among pollen-containing flora. The pollen sticks to their bodies and is carried to the next pistillate, or female

flower, which the bees pollinate.

researchers moved on to part Bee.

During the kiwi flower

blooming season, the

researchers in Buenos

Aires conditioned

bees at an orchard

with sugarcontaining

KM.

Following the

c ond it ion i n g

period, the

activity of

the hive was

q u a n t i f i e d

based on the

number of bees

that left the colony

and the amount and

type of pollen that the

foraging bees brought back

to the hive.

“In the blooming period of kiwi

f lowers, there are other blooming

f lowers containing nectar,” Farina

said. The bees would be more attracted

to the nectar-containing f lora, so the

number of bees that go to kiwi f lowers

will continuously decrease.

“But remember that the colonies

of honey bees are around sixty to

seventy thousand. With even ten

percent or five percent of bee

activity at the nectarless kiwi

crop, that is a decent amount

of activity still,” Farina said.

“And when the food or other

bioindicators are transferred

from one individual to another,

this will establish and promote

long-term intensive activity onto

the target crop throughout the hive.”

Despite the potential benefits of

conditioning bees to target nectarless

crops, it's important to note that this

strategy does not come without its

drawbacks. Yes, conducting longer

and more expansive studies involving

conditioned bees will help to evaluate

the efficacy of the mimic aroma and

the potential of the target pollination

strategy. And yes, developing synthetic

aromas for various nectarless crops that

bees are normally unable to distinguish

other plants by scent is also a necessity.

All of these are valid considerations that

must be resolved before the findings

from Farina and his lab are actually

applied. But perhaps most

important to examine

when considering the

future of this field

is the danger that

comes to bees

when foraging

on agricultural

land.

“It is important

to

shorten the

period in

which bees are

conditioned…

[in order to]

reduce the time

bees are exposed to

agricultural environments,”

Farina said. “The use of agrochemicals

and poor biodiversity…[make] these

agricultural environments very

disturbed and pose risks to honey

bee health.”

If the targeted crop strategy is

implemented, it is important to

be cognizant of the underbelly of

pollinator-based agriculture methods.

If we aren’t cautious about how we

augment the complex environmental

systems of our world, we risk disrupting

global ecology by debilitating the

pollination activity of bees. On the

other hand, there is also a possibility

of improving agricultural productivity,

even for nectarless crops that often

go unforaged by pollinators, which

provide an invaluable service to f lora

and to us. ■


FEATURE

Environmental Science

THE HURRICANE

WHISPERER

BY JIYA MODY AND EPHRAIM CHO

PREDICTING THE

NEXT CYCLONE

ART BY KARA TAO

Rosimar Rios-Berrios’s journey from

being a young girl in hurricaneprone

Puerto Rico to a leading

atmospheric scientist is as inspiring as it is

impactful. Raised on the small Caribbean

island, often described as the “Hurricane

Highway,” her early life was shaped by

powerful storms—now, her research

reveals a new way to predict hurricanes

weeks in advance.

“Growing up, my family and I

experienced firsthand the direct impacts

of hurricanes,” Rios-

Berrios said.

In 1998,

when she was just nine years old, a

Category Three hurricane devastated her

community, and her friends and neighbors

lost everything. This event—and others

like it—fueled her determination to better

understand these natural forces, initially

as a television meteorologist. But as she

embarked on her undergraduate studies

in physics at the University of Puerto Rico,

specializing in meteorology, her passion for

research began to take shape.

Rios-Berrios’s academic journey took

a pivotal turn during her PhD at the

University at Albany, New York, where

her focus shifted to the complex science of

tropical cyclogenesis—the process by which

tropical storms and hurricanes form. It was

during this time that she became interested

in the phenomenon of atmospheric

Kelvin waves—large-scale disturbances

in the atmosphere that

some scientists had long

suspected influenced the

development of hurricanes.

Kelvin waves typically

consist of large clusters of

clouds and precipitation,

and their presence can

influence wind patterns,

temperatures, and

overall atmospheric

circulation. They

propagate eastward

along the equator but

can also affect areas

to the north and south

of the equator. Kelvin

waves can increase or

decrease the amount of

precipitation over tropical

oceans and lands, including

agricultural areas over South America

and Africa. Initially, Rios-Berrios was

fascinated by the potential role of Kelvin

waves in tropical cyclone formation but

lacked a robust way to explore this topic in

further detail so early in her PhD.

The right time came along during Rios-

Berrios’s postdoctoral research at the

National Science Foundation National

Center for Atmospheric Research, when

she was tasked with coming up with a new

research topic. Supported by a fellowship

that allowed her academic freedom, Rios-

Berrios finally delved into Kelvin waves,

deciding to focus on tropical cyclogenesis

and its variability rather than the dynamics

of already-formed hurricanes.

One of her key tools during this phase

was an “aquaplanet” model. The Earth is a

complicated system, and there are a lot of

factors that explain when, where, and why a

hurricane forms. This, unfortunately, makes

it incredibly hard for researchers to analyze

how Kelvin waves affect cyclogenesis. To

solve this problem, Rios-Berrios, along with

co-researchers Brian H. Tang, Christopher

A. Davis, and Jonathan Martinez, utilized

an atmospheric model developed by the

National Center for Atmospheric Research

to create an aquaplanet—a simplified

version of Earth—as a model substitute.

The aquaplanet has no land, seasons, El

Niño, or La Niña. Thanks to its simplicity,

the aquaplanet allows scientists to isolate

any combination of factors to see how they

specifically affect hurricane formation while

maintaining the physical characteristics of

Earth—and thereby the model’s validity.

Using this framework, Rios-Berrios’s

team planned to isolate the role Kelvin

waves play in hurricane formation. But


Environmental Science

FEATURE

first, she needed to answer a crucial

question: How precisely could they find

and track Kelvin waves?

To locate Kelvin waves, the team

used a technique called spatiotemporal

filtering to analyze rainfall rates in the

aquaplanet. In simple terms, rainfall

rates were detected and plotted over a

period of time and longitude, which was

shown in previous studies to indicate

the presence of Kelvin waves. To detect

hurricanes and cyclogenesis in the

aquaplanet, a different approach was

needed. Hurricanes present certain

features in the atmosphere that scientists

can use to detect the existence of

hurricanes and their potential movement

and location. Rios-Berrios’s team used

an algorithm called TRACK to perform

this analysis, which looked specifically

for a circulation to identify cyclones.

From here, it was onto the fun part—

finding out whether Kelvin waves were

really a major cause of cyclogenesis, and

what that connection might entail.

After identifying Kelvin waves, the team

tracked the relationship between Kelvin

waves and hurricanes by recording the

amount of time between when a Kelvin

wave passes a longitude and when the

cyclone actually forms at that same

longitude. The team found that there

was a statistically significant correlation

between Kelvin wave crests and hurricane

formation. The results showed that, on

average, a hurricane is twice as likely to

develop two days after the Kelvin wave

reaches its “crest,” or highest point. Because

the aquaplanet simulation still retains

many of the same characteristics as Earth,

these results suggest that Kelvin waves

are not only correlated with hurricane

formation, but may indeed help induce it.

Rios-Berrios’s research shows that these

atmospheric waves can strongly increase

the likelihood of storm development by

augmenting atmospheric conditions that

are conducive to the birth of tropical

cyclones. This discovery has opened

the door to new possibilities in the

long-standing challenge of predicting

hurricane formation.

With current methods, scientists

can predict hurricanes only a few days

in advance. However, Rios-Berrios’s


Hurricane Matthew, which struck Haiti in 2016, is captured from an aerial viewpoint.

research offers the possibility of extending

this window to one or even two weeks.

Her work suggests that monitoring Kelvin

waves could provide early indications

of periods of heightened tropical

cyclone activity, offering a potential

breakthrough in the science of hurricane

forecasting. “We could start thinking

about anticipating one week, two weeks

ahead of time,” Rios-Berrios said.

Imagine this: forecasters could issue

warnings of potential hurricane activity

weeks in advance, giving communities

in vulnerable regions—such as Rios-

Berrios’s native Puerto Rico—more

time to prepare and mitigate the effects

of storms. This would be a dramatic

improvement to current methods, where

the lack of adequate time for cities and

countries to prepare has claimed the lives

of hundreds of thousands of people.

Rios-Berrios’s work also has significant

implications in the context of climate

change. As the planet warms, hurricanes

are becoming more intense, driven by

higher sea surface temperatures and

increased atmospheric moisture. Her

research raises important questions about

how Kelvin waves—and, consequently,

hurricanes—might behave in a changing

climate. Will these waves become

stronger or more frequent, leading to

more powerful storms? Or could changes

in global atmospheric patterns reduce

their influence?

Answering these questions will require

significant advances in climate modeling,

IMAGE COURTESY OF NASA GODDARD PHOTO AND VIDEO

especially in how these models simulate

the intricate relationships between Kelvin

waves and tropical cyclones. While

current models provide useful insights,

they lack the detail necessary to fully

capture these complex interactions.

“They’re very powerful, but unfortunately,

they cannot resolve all the fine details of

tropical cyclones,” Rios-Berrios said. “So

I think we need to spend more resources

and continually improve our climate

models so that they can give us certain

information about how hurricanes will

change in the changing climate.” Overall,

improved models will be crucial for

understanding the future of hurricane

behavior in a warming world.

Rosimar Rios-Berrios’s journey is

not just about scientific discovery; it’s

a deeply personal mission. From her

early experiences in Puerto Rico, where

hurricanes were a deadly threat, to her

cutting-edge research on the atmospheric

forces that drive storm formation, her

work is rooted in a desire to help others.

Her research stands as a beacon of hope

for communities like her own, which

face the brunt of these natural disasters.

When asked what she would say to a

younger version of herself, she said, “Our

atmosphere is a lot more complex than we

think it is. And even though hurricanes

can be very destructive, there is a lot we

don’t know about them. And so, pursuing

a career in research to understand how

hurricanes form and become strong could

be very interesting.” We agree. ■


SHORT

Profile

NIKITA PAUDEL

YC ’25

BY LYNN DAI

When Nikita Paudel (YC ’25) got her first menstrual

period at age eleven, she was escorted to another

room to have dinner away from her family. “You get to

watch TV and eat dinner in this room,” she recalled her mother

saying. To Paudel, that experience was a first-hand account of

the restrictions many families in Nepal place on women who are

actively menstruating. “[My dad] told my mom, ‘If you treat Nikita

like this, you might as well throw her out of the house,’” Paudel said.

“I experienced firsthand how much of a voice men have in shaping

menstruation experiences.” The stigma that these traditions place

on the menstruation process is often further exacerbated by a lack

of access to sanitary products.

Paudel established an education company called Pyari in January

2023 with co-founder Priyanshu Pokhrel, a junior at Wesleyan

University, to address this inequity in menstruation from the

cultural and structural aspects of menstrual health management.

Pyari, meaning “cutie” or “lovable” in Nepali, is a direct rejection

of the traditional view of menstruation as impure. The initiative

branched out from an Environmental Studies course Paudel took

on Sustainable Development Goals (SDGs) and Implementation.

While Paudel initially planned to establish Pyari as an initiative

to teach young women to sew reusable pads, the varying access to

basic hygienic products like soap or irons that women had in Nepal

led her to shift Pyari’s focus to education. She later engaged the

local ward and school committee chairperson in a presentation to

increase awareness of the need for menstrual health and sanitation.

“What we’re hearing from the government and schools is they

don’t have the time, resources, or manpower to improve the

[sanitation infrastructure],” Paudel said. “So that’s where we want

to fill that gap by really understanding the community’s needs and

identifying the mismatch.”

One of the earliest roadblocks Paudel ran into was the diversity

of cultural practices restricting equitable access to menstrual

health. While the Pyari team had conducted extensive research

into the hygiene infrastructure of various cities in Nepal—Syangja,

Bajura, and Kathmandu—they found their work “went out the

window” once they talked to residents in these communities. Last

summer, the team conducted a needs assessment in Syangja with

over fifty stakeholders to evaluate hygiene and menstrual health

management issues and skill management.

“I think there’s a common misconception of the cultural stigmas

surrounding menstrual health in Nepal,” Paudel said. “These

taboos are actually very different geographically: there are some

parts of Nepal where residents have never heard of the practice

of restricting menstruation, but there are also other areas

like Bajura, where women have to participate in Chhaupadi, a

[practice] banning them from the house. We were able to really

understand the full breadth of how intricate this was across

Nepal and then figure out ways to be targeted no matter what

IMAGE COURTESY OF PYARI EDUCATION PVT. LTD. AND SWARNIMA SHRESTHA

COMMUNICATED BY ALYSSA ANDERSON

The co-founders of Pyari, Nikita and Priyanshu, stand by their booth.

community we went to.”

As a result, Paudel has developed guidelines to target the

different restrictions of menstrual health equity and, in some cases,

translate their educational materials between dialects like Nepali

and Bajurali.

Paudel began placing more emphasis on education in an effort

to spark a cultural shift, targeting children around the time they

experience their first period so that the conversation could start

earlier rather than later. “We began focusing more on education to

try and cause a cultural shift by starting with children around the

time they receive their first period, so we can get the conversation

going early instead of later,” she said. These educational initiatives

include in-person lectures to facilitate interactiveness between

students and Pyari’s volunteers and create awareness for students

in Nepal to engage with the direct action of touching a menstrual

pad and tampon. Meanwhile, Pyari aims to station volunteers

around Nepal to check the quality of water and create pictographs

for kids to understand the steps of hand-washing and disposing

of pads.

In a documentary filmed by Thibeaux Hirsh, a member of

Pyari who is currently a senior at Wesleyan, there is a scene of

a little boy in the Syangja community running up to Paudel and

asking to express his opinions about the importance of respect

for the film. “Building empathy early on is the ultimate goal of

all of this,” Paudel said, speaking of the prevalence of domestic

violence and sexual abuse in South Asia. “That’s why we start

that conversation early: to get boys and girls to understand each

other earlier on. If we’re able to do that, that will be the thing I’m

proudest of,” she said. ■


Profile

SHORT

JACOB ELDRED

YC ’24

BY CHLOE ALFONSO

Every year at commencement, ceremonial maces

are displayed and paraded through Old Campus. A

gleaming trident hangs in the Grace Hopper dining

hall. In Morse, a neon axe looms over students as they eat

dinner. What do this mace, trident, and axe have in common?

The answer: Jacob Eldred.

In his four years at Yale as a mechanical engineering

major, Eldred built a legacy for himself through art and

engineering. He designed the mace, trident, and axe to

hold symbolic significance that far exceeds their decorative

value. The Yale School of Engineering and Applied Science

only became its own school in 2022, and Eldred’s mace

represented this autonomy. Grace Hopper College was

renamed in 2017, and the trident symbolized revived student

spirits and a reckoning with Yale’s history. After the isolation

imposed by the pandemic, the axe was an electric start to

Morse’s homecoming.

“[My work] comes from a place of understanding

materials and manufacturing. Some art is interested in

form and tries to hide the fabrication techniques, but I

am more interested in being guided by the constraints of a

technique,” Eldred said.

While some might think that art and engineering are

different, Eldred is a firm believer that the two crafts are very

similar if approached in a specific way. “To me, the problem

solving in sculpture and mechanical engineering are very

similar. There are no arbitrary shapes. Beyond cost, structure,

and fabrication, engineers might consider heat or vibrations,

and artists might attach political or historical ideas to their

forms, but the method of creating shapes that make sense

within some value system [is] the same,” Eldred said. When

talking about how to synthesize art and engineering, Eldred

offers a piece of advice: everyone should take some form of

a craft class, even if just to make small things to decorate

a dorm room. “Exerting control over your environment

and making physical objects are two of the most satisfying


IMAGE COURTESY OF JACOB ELDRED COMMUNICATED BY CHLOE ALFONSO

Eldred designed a mace for the Yale School of Engineering & Applied Science.

IMAGE COURTESY OF SAM KARP COMMUNICATED BY CHLOE ALFONSO

Eldred proudly holds the trident he created for Grace Hopper College.

things a person can do,” Eldred said.

Three months after graduating, Eldred reflects on his time

at Yale fondly. When not designing nine-foot neon axes or

building machines to study the coronavirus, Eldred loved to

listen to the many speakers that visited Yale, with the goal of

seeing five to ten speakers per term. He recounts incredible

talks from film directors and Nobel laureates and still

remembers missing one speaker by three seats on the waitlist.

When asked about his favorite classes, Eldred mentioned

that he made sure to take as many non-engineering classes

as possible, two of his favorites being on Indian national

security and the nature and politics of rivers. And, of course,

some of his favorite memories are in the MechE shop, a

guided workspace available to students, and making art with

his mentors Nick and Vinny Bernardo at the SEAS and Gibbs

shops at Yale. Eldred said he cannot thank them enough:

“They are brilliant machinists and thoughtful teachers, and

they helped shape how I see the world by working with me

on all of my projects.” Nick helped on the axe and the trident,

while Vinny made the first machine Eldred ever designed for

a lab. These two mentors were originally trained as manual

tool and die machinists but are able to make anything out of

metal, Eldred said. “It was a privilege working with them,

and Yale should do everything it can to keep well-staffed

shops open to students. If they weren’t here, I would have

received half the education I did,” he added.

Currently, Eldred is pursuing a masters in mechanical

engineering at Stanford University. Although he now lives

on the other side of the country and is represented by a tree

instead of a bulldog, he will always be a part of Yale for what

he was able to give it: community. ■


WHY WE DIE

UNVEILING THE SECRETS OF AGING AND

THE QUEST FOR IMMORTALITY

BY ANNIE YE

SCIENCE

IN

IMAGE COURTESY OF WIKIMEDIA COMMONS

For many of us, the idea of dying evokes so much fear that we would rather

approach it with denial—to view death as something that happens to

others, rather than to ourselves. In his recent book, Why We Die: The New

Science of Ageing and Longevity, Nobel laureate Venki Ramakrishnan defines

death as something much more systematic. For him, it is simply when the cells

of our body stop working as a coherent unit. In his book, Ramakrishnan details

the various approaches scientists have taken to combat death, and he questions

whether we should even want to live forever at all.

Ramakrishnan brings the rigor and curiosity of a scientist to his description

of the many breakthroughs of the past century in aging research. He draws upon

his expertise from his decades-long career, which includes conducting research

in biochemistry at Yale, the Brookhaven National Laboratory in New York,

and the Medical Research Council Laboratory in Cambridge, U.K. Throughout

the podcast, Ramakrishnan reminds readers of how far we’ve come. Modern

research, including improvements in vaccines and sanitation, has increased life

expectancy significantly, he reiterates.

In recent years, scientists have attempted to fight death in a variety of ways.

Ramakrishnan details each of these methodically, facilitating discussions about

death by characterizing it simply as a scientific question. He explains how aging

arises due to telomeres, proteins on the end of chromosomes that shorten with

age, causing cells to stop dividing. In response, scientists have explored modifying

telomere lengths to slow aging. Ramakrishnan also summarizes studies showing

that calorie restriction can elongate lifespan and details scientists’ subsequent

attempts to modify the TOR gene, which functions to regulate cell growth and

metabolism, to produce similar results. Some scientists are even exploring

methods of protecting control proteins from aging, which regulate protein

production and are more prone to error as we age.

However, in a larger quest for immortality, Ramakrishnan tells readers that

most of these results seem to be dead ends. Changing natural telomere length

may lead to cancer, adjusting the TOR gene could increase risks of infection, and

the process by which proteins age is still unknown. Despite these many “failures”,

Ramakrishnan focuses on the valuable lessons learned through each experiment,

finding more value in the journey of the research process than the ultimate end.

As scientists may be getting closer to curing death, it is important to consider

the social ramifications of this breakthrough. Lengthening life span would

significantly increase the world population, as well as the population of elderly

that require intensive care. Moreover, Ramakrishnan warns that even if we

could postpone death, we would still lose significant intellectual and physical

capabilities as we age. Overall, Ramakrishnan states that societies may not be

prepared for the consequences of prolonged life. And if this is the opinion of a

scientist with decades of experience in the aging industry, perhaps it’s best if we,

as the public, simply sit back and enjoy our lives, however long we have. ■


QUIRKS AND QUARKS

THE BEST OF SCIENCE AND STORYTELLING

BY VICTORIA TAN

For decades, spaceflight has captivated humanity’s imagination. A podcast

called Quirks & Quarks capitalizes on that interest. Hosted by Bob McDonald,

this podcast has brought the most cutting-edge discoveries in physics and

natural sciences to its listeners for over forty years. They’ve explored topics ranging

from the mysteries of gravity to pandemic virus research; fittingly, their website

describes it as covering “the quirks of the expanding universe to the quarks within

a single atom…and everything in between.” McDonald is an experienced program

host and science correspondent, owing to his work at the Ontario Science Centre.

Quirks & Quarks recently hosted a particularly special segment for both its

namesake and host—one that discusses the health risks of space travel. In this

segment, McDonald explored the consequences of space missions on human health

with a leading expert on the topic: Susan Bailey, a professor at Colorado State

University’s Department of Environmental and Radiological Health Sciences. Bailey

has contributed extensively to the repository of research on the effects of space

travel on health, including NASA’s famed twin study on astronauts Scott and Mark

Kelly, which analyzed the physiological, cognitive, and molecular changes that space

travel had on a human’s body. In total, the repository amounts to a collection of over

forty manuscripts from more than twenty-five countries, all of which will provide

answers to the intricate questions that arise about the relationship between space

travel and human health.

In the nearly nine-minute segment, McDonald asked Bailey a variety of thoughtprovoking

questions. For example, he wanted to know how quickly physiological

changes could occur once the astronauts traveled into space. Bailey discussed the

SpaceX Inspiration4 mission frequently, which provided insight into comparisons

between civilians and trained astronauts, as well as the effects of short and long

space travel times. Both McDonald and Bailey agreed about the implications of

space travel on telomeres—protective caps on chromosomes that are crucial for

cellular aging and have long-term consequences on health. It was found that no

matter the length of spaceflight time, all travelers exhibited shorter telomere lengths

upon returning to Earth.

THE

SPOTLIGHT

Later in the segment, Bailey brought in an outside expert—Christopher

Mason, one of the principal investigators in NASA’s twin study and a professor

of Genomics, Physiology, and Biophysics at Weill Cornell Medicine—to discuss

the limiting effect of radiation exposure. Radiation is one of the most harmful

threats that spaceflight poses to humans, causing DNA damage, mitochondrial

dysfunction, and changes in the microbiome. These findings showcase that no

matter what, the current technological capabilities do not allow for safe backand-forth

travel between Earth and outer space, at least for extended periods.

The segment ended on this slightly somber conclusion, but one note of hope

rang through. “There’s no place like Earth,” McDonald said. And indeed, listeners

are left to ponder that if humans were able to send rockets, satellites, and people

beyond the confines of our atmosphere to explore outer space, it is only a matter

of time before they are also able to find ways to do so more safely. ■




COUNTERPOINT

UNVEILING

CHICXULUB

The Asteroid That Changed

Earth’s History

Stegosauruses ruffle through ferns; a

lone velociraptor hunts in the desert;

brachiosauruses bite leaves from ginkgo trees;

a triceratops family looks up to see a flaming ball

of fire plummeting towards Earth. This is one of

the most recognizable scenes from our knowledge

of Earth’s history. The Chicxulub crater under the

Yucatán Peninsula of Mexico, where the Chicxulub

asteroid left its mark, tells the story of how the

mass extinction of the dinosaurs paved the way for

the reign of mammals and, consequently, humans.

But this crater also contains fascinating evidence

of this famous asteroid’s extraterrestrial origins.

Scientists have debated whether an icy comet or

a rocky, metallic asteroid caused the Cretaceous-

Paleogene extinction. A new research study led

by Mario Fischer-Gödde from the University of

Cologne supports the latter theory and provides

solid evidence for a new perspective: the Chicxulub

asteroid was formed much further out in space

than previously thought.

Fischer-Gödde came to this conclusion after

analyzing samples taken from the Chicxulub

impact zone. In order to differentiate between Earth

soil and traces of ancient meteorite material, the

research team chose to measure the concentration

of ruthenium, an element that tends to be more

abundant in meteorites. Ruthenium has various

isotopes whose concentrations vary depending on

the meteorite type. When the team analyzed the set

of isotopes present in the soil, they found that the

data was most similar to the typical concentration

of ruthenium isotopes in carbonaceous chondrite

(CC) meteorites. Concentrated amounts of CC

meteorites in the soil from the impact zone suggest

that Chicxulub was a carbonaceous asteroid. These

By Hannah Dirsa


types of asteroids form at distances beyond the

orbit of Jupiter.

Most of the meteorites on Earth are from

siliceous asteroids, which are formed in the inner

solar system. So as prevalent as Chicxulub is in

textbooks about Earth’s history, it is a relatively

rare phenomenon to happen to Earth. How did

an asteroid from more than 440 million miles

away make its journey to Earth? One guess is that

gravity pulled some carbonaceous asteroids into

our solar system, causing them to settle into the

Main Asteroid Belt between Mars and Jupiter.

However, there is no definite answer.

The analysis technique used by the Fischer-

Gödde research team may be very useful for

future studies about meteorite impacts on Earth.

The team also took samples from five impact

zones that were thirty-six to 470 million years

old, as well as samples from sedimentary

deposits called spherule layers that were

3.2 to 3.5 billion years old. The ruthenium

concentrations showed that the younger impact

sites had meteorites from siliceous asteroids. On

the other hand, the ruthenium in the spherule

layers aligned with carbonaceous asteroids. In

the future, ruthenium isotopes could be used in

experiments to investigate more impact sites and

study meteor collision trends at various points

in Earth’s history.

The fact that the rise of humanity was dependent

on an asteroid that, from over 440 million miles

away, came to Earth on an extraordinarily specific

collision course, could be an inspiring or disturbing

revelation. Nevertheless, one thing is for certain:

the history of the Earth is still a mystery to us,

and many answers are right at our fingertips. ■


BY ALYSSA ANDERSON

On November 5, 2024, American citizens will cast their

votes in the presidential election. Casting a ballot is

inevitably influenced by the weeks and months of

candidates’ campaigning that precedes it: commercials, billboards,

yard signs, and mail displaying Harris’s and Trump’s policies and

beliefs. But how much do we really know about how campaigns

are designed and the scientific strategies that inform them? Joshua

Kalla, an associate professor of political science and statistics and

data science, teaches a course called “Data Science for Political

Campaigns,” an interdisciplinary class offered every fall that

explores the structural and scientific underpinnings of electoral

campaigns and how they drive voting decisions.

Kalla’s course approaches both past and present political

campaigns with the rigor of data science analysis. As an

introductory course, it is meant to be an introduction to data

skills, computational social science, coding, and statistics, as

well as an application of those topics to the world of elections

and campaigns.

Before introducing this course, Kalla worked in data analytics

for political campaigns and researched how campaign tactics can

impact voting decisions. “One of my colleagues once told me that

a lot of my research ruined cocktail parties,” Kalla said. People

have inflated expectations about how influential the things that

they’re working on—what they are funding, what doors they’re

knocking on, or what TV ads they’re buying—are, he said. “But

a lot of my work is about how most of what’s done in American

campaigns tends to be minimally to not effective at all,” Kalla

said. This revelation about the minimal impact played by

election campaigns is just one of the many insights students are

able to garner.

In this course, students study polling, create representative

samples for surveys, analyze election results, and explore

persuasion techniques. One topic Kalla examines is likely

voter screening. In a campaign, the only important

polling demographic is the people

who actually vote in the election,

otherwise known as likely

voters. Data scientists can’t

simply poll everyone who

claims they will vote

because, in reality,

these predictions

often fall short.

Therefore, samples

for polling are built

based on voters’

history in order

to minimize the

CROSS

DATA SCIENCE FOR

POLITICAL CAMPAIGNS

IMAGE COURTESY OF ALYSSA ANDERSON

Kalla explains the Python coding concept of floating point arithmetic.

chance that a non-voter gets a say in a poll that won’t

impact them.

Beyond polling, accuracy in surveys is another topic

that arises frequently in the class and is a fundamental

aspect of understanding political data science. Politicians

rely heavily on public surveys to gauge voter satisfaction.

Because of this reliance, students consider how details

of a survey, including how questions are phrased,

can critically impact responses. Using non-leading

questions, data scientists can gather more unbiased

data, allowing politicians to accurately analyze the

effectiveness of their campaigns.

Kalla’s 130-student course meets once a week and

offers an interactive environment filled with student

engagement and excitement. Each 110-minute class

meets in a half-lecture and half-group lab format. “The

labs are a way for them to practice those coding skills

and the substantive skills of what we’re covering in

class,” Kalla said. The final project prompts students

to find real data in the world of politics and answer

a question about it using the data analysis and coding

skills that they’ve learned throughout the class.

This class allows students interested in politics to

engage with it in a data-intensive way, serving as an entry

point into the computational social sciences. “And on

the flip side, there are a lot of students who come from

a statistics and STEM background who are craving to

learn more about applications of the kind of stuff that

they’re learning, and this is a great opportunity for them

to do that,” Kalla said. So, whether you come from a

background in social science, statistics, or STEM, PLSC

347 acts as a great meeting point for coders, STEM

enthusiasts, and passionate politicians alike. Because

who knows? Maybe you, with the use of data science

and Python 3, could help elect the next president of the

United States. ■

ROADS

ART BY KARA TAO



Interested in getting involved with

Yale Scientific

for writing, production, web,

business or outreach?

Learn more at

yalescientific.org/get-involved

D_Yale_SC_ENG_half_FALL_10_19qxp.qxp_8 10/7/19 12:05 PM Page 1

Welcome to Yale!

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.

We are excited to be a part of your Yale journey, and we look forward to

supporting you at Yale and beyond!

Join us at: ysea.org

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