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Yale Scientific<br />

THE NATION’S OLDEST COLLEGE SCIENCE PUBLICATION • ESTABLISHED IN 1894<br />

MAY 2023<br />

VOL. 96 NO. 2 • $6.99<br />

FATAL<br />

ATTRACTION 22<br />

TRACKING CARBON’S<br />

UNDERWATER DIVE 12<br />

IT’S IN OUR BONES 14<br />

16<br />

ACNE-BIOTICS<br />

ANIMALS AGAINST<br />

19<br />

RISING TIDES


TABLE OF<br />

VOL. 96 ISSUE NO. 2<br />

COVER<br />

22<br />

A R T<br />

I C L E<br />

Fatal Attraction<br />

Cindy Mei<br />

Tsetse flies are responsible for spreading a deadly disease that leads to agricultural and medical<br />

devastation in Africa. The Carlson lab at Yale and their collaborators have identified a pheromone<br />

produced by the fly that may be able to attract and halt the activity of the flies, which holds great<br />

potential to control the tsetse fly population.<br />

12 Tracking Carbon's Underwater Dive<br />

Tori Sodeinde<br />

Many marine animals form calcium carbonate shells that deposit minerals onto the surface of the<br />

Earth, but billions of years ago, before these biotic carbonate sources evolved, what were the most<br />

important contributing sources to the precipitation of carbonate? New geological isotope data<br />

challenges previous ideas about the ancient history of the marine carbonate factory.<br />

14 It's in Our Bones<br />

Evelyn Jiang<br />

Researchers at Yale have uncovered a key molecular link between bone marrow aging and the<br />

development of atherosclerosis—which causes heart attacks, strokes, and other cardiovascular<br />

complications, which are collectively the leading cause of death worldwide. Their findings offer<br />

new hope for the treatment and prevention of the disease.<br />

16 Acne-Biotics<br />

Crystal Liu<br />

Yale structural biologists determined the structure of a promising acne-fighting antibiotic, sarecycline,<br />

in complex with the ribosome of C. acnes, the bacterium largely responsible for acne. Read about<br />

sarecycline’s mechanism, why it can be more effective than other antibiotics, and other discoveries<br />

about the C. acnes ribosome.<br />

19 Animals Against Rising Tides<br />

Abigail Jolteus<br />

Global warming is causing sea levels to rise rapidly, which imposes stress on coastal ecosystems. Researchers<br />

at the Yale School of Environment and the University of Florida have investigated the impact of mussels<br />

on salt marshes, which could help provide more insight into how to help mitigate the effects of sea level<br />

rise —one of the most urgent climate threats today.<br />

2 Yale Scientific Magazine May 2023 www.yalescientific.org


CONTENTS<br />

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

4<br />

6<br />

25<br />

34<br />

Q&A<br />

NEWS<br />

FEATURES<br />

SPECIALS<br />

What is the World's Most Efficient Form of Urination? • Victor Nguyen<br />

Who were the First Cowboys in the World? • Jamie Seu<br />

The Changing Language of Our Changing Climate • Pratiksha Bhattacharyya<br />

Saving Birds on Yale's Campus • Mia Gawith<br />

A New Approach Against an Old Foe • Johnny Yue<br />

Taking a Peek at Pandora's Cluster • Ignacio Ruiz-Sanchez<br />

Sink or Swim • Lea Papa<br />

Using Machine Learning to Produce Metallic Glass • Maya Khurana<br />

A Dynamic Duo Fighting Against Brain Cancer • Casey McGuire<br />

The Carbon Footprint of Care • Jessica Le<br />

Wooden Corkscrew Robots Plant Seeds • Madeleine Popofsky<br />

Your Unique Fingerprint • Elisa Howard<br />

The Impossible Star • Elizabeth Watson<br />

Cyborg Zebrafish • Nathan Mu<br />

How Ancient Humans Escaped the Ice Age • Matthew Blair<br />

Plant-Animal Hybrids • Samantha Liu<br />

Undergraduate Profile: Charnice Hoegnifioh (YC '24) • Emily Shang<br />

Alumni Profile: Amymarie Bartholomew (YC '13) • William Archacki<br />

Science in the Spotlight: Measure for Measure • Henry Chen<br />

Science in the Spotlight: the Darkness Manifesto • Faith Pena<br />

Counterpoint: Quantum Cryptography • Matthew Dobre<br />

Perimeter • Sophia Zhao<br />

www.yalescientific.org<br />

May 2023 Yale Scientific Magazine 3


WHO WERE THE<br />

FIRST COWBOYS IN<br />

THE WORLD?<br />

&<br />

WHAT IS THE WORLD'S<br />

MOST EFFICIENT<br />

FORM OF URINATION?<br />

By Victor Nguyen<br />

Has inspiration ever hit you while you were on the toilet? For<br />

scientists studying the potty period of the glassy-winged<br />

sharpshooter, a half-inch-long insect in the Cicadellidae<br />

family, a revelation between physics and biology was born. Known to be<br />

serious agricultural pests, sharpshooters relieve themselves by forming<br />

small droplets of urine at their anal styluses, which are appendages<br />

involved in excretion. Eventually, the droplets grow to a diameter of<br />

0.725 millimeters, and the anal styluses launches the particulates<br />

repeatedly, accelerating up to forty times the force of gravity.<br />

Sharpshooters developed this bathroom behavior due to their waterheavy<br />

diets. The leafhoppers feed on plant xylem sap, which has a small<br />

nutrient-to-liquid ratio. As a result, they drink up to three hundred<br />

times their body weight. A closer analysis of this phenomenon,<br />

published by researchers at Georgia Tech in Nature Communications,<br />

showed that sharpshooters developed this biological mechanism to<br />

conserve energy given their small size and energy output.<br />

The sharpshooter’s urinary facilities mark a notable discovery because<br />

they are the first observation of superpropulsion in a biological system,<br />

a phenomenon in which a projectile moves faster than the launcher<br />

that propelled it. Applications of the sharpshooter’s mechanisms have<br />

a future in electronics. Researchers investigating the sharpshooters<br />

foresee how the insect’s energy-efficient solution can be used to remove<br />

solvents in micro-manufacturing or to eliminate water from complex<br />

surfaces. This intersection of the physical and biological sciences sets<br />

a precedent for finding unorthodox answers. Wherever and whenever<br />

inspiration or the need to relieve strikes, innovation may soon follow. ■<br />

By Jamie Seu<br />

Stirrups. Leather boots. The Wild West. Cowboys have been<br />

a subject of fascination for centuries, appearing in every<br />

aspect of American pop culture from cliché Halloween<br />

costumes to Hollywood blockbusters. However, the modern<br />

perception of these equestrian cavaliers encapsulates only a<br />

minuscule piece of the long, intertwining history of humans<br />

and horses—a history that, according to recent archaeological<br />

findings, could date back over five thousand years.<br />

While evidence of equine domestication has been welldocumented<br />

throughout history, proof of ridership and determination<br />

of the practice’s exact origins have been difficult to establish. In a<br />

paper published in Science Advances, a team of researchers from<br />

Finland, Romania, Bulgaria, Hungary, and New York analyzed over<br />

two hundred skeletal remains to unravel these mysteries. They found<br />

the earliest bioanthropological evidence of horseback riding to date<br />

in the skeletons of five Yamnaya individuals, a people noted for their<br />

expansion across Eurasia during the Early Bronze Age in the third<br />

millennium BC. Each skeleton was analyzed according to six specific<br />

criteria indicative of “horsemanship syndrome.” The five skeletons<br />

displayed at least four of the six traits, including wear on the pelvis<br />

and femur, stress-induced vertebral degeneration, and alterations in<br />

certain bone shapes and sizes.<br />

The use of horses as a mode of transportation marked a dramatic<br />

transition in societal evolution, dictating patterns of migration and<br />

facilitating trade between previously isolated locations. So while the<br />

first cowboys were not quite the gun-toting, saloon-loving buckaroos<br />

we make them out to be, they—and their speedy, four-legged sidekicks<br />

—may have been some of the most influential figures in history. ■<br />

4 Yale Scientific Magazine May 2023 www.yalescientific.org


The Editor-in-Chief Speaks<br />

THROUGH THE LOOKING GLASS<br />

This summer, I had the immense privilege of interviewing Dr. Vivek Murthy,<br />

the 19th and 21st U.S. Surgeon General and an alumnus of the Yale School<br />

of Medicine. When asked about the role of science journalism in our society,<br />

Dr. Murthy told me, “There could not be a time in my life where I think we have<br />

needed science journalists more to be there for us explaining what people need to<br />

know in a world where we’re awash in misinformation.”<br />

Indeed, with the polarization of online forums and social media platforms,<br />

conspiracy theories are spreading like never before, while the public’s distrust in the<br />

notion of ‘experts’ has rapidly grown. How, then, can we bridge the chasm that has<br />

emerged between science and society?<br />

There is no simple or straightforward answer, but as Dr. Murthy emphasized,<br />

science journalism plays a pivotal role in connecting the two. While I would<br />

typically use this space to tell you about the articles in this issue, I found it would<br />

be fitting to re-examine the mission of the Yale Scientific itself. At its core, our<br />

work strives to highlight the relevance of recent innovations in our daily lives,<br />

spark scientific interest in youth, help communities make informed decisions, and<br />

build public trust in science. We aim to present scientific, medical, and engineering<br />

discoveries to a general audience—no matter their background—in an accessible<br />

and unbiased manner.<br />

Recently, we’ve had the privilege of poring through the archives from the <strong>YSM</strong><br />

offices in Welch Hall on Old Campus and in 305 Crown St. Flipping through the<br />

yellowing pages of our hand-bound volumes from the 19th century and learning<br />

about the history of the Yale School of Medicine, the Sheffield Scientific School,<br />

and the Yale Scientific Magazine itself has revealed that while a lot has changed,<br />

our central mission has remained steadfast. In fact, it has only been reaffirmed as<br />

science has become the center of attention in debates surrounding deeply divisive<br />

issues, ethical concerns, and public policy controversies. At <strong>YSM</strong>, we will continue<br />

to question the assumed, communicate the abstract, and weave distinctly human<br />

stories around technical scientific developments.<br />

I am honored and humbled to continue the Yale Scientific’s long legacy of<br />

science journalism alongside our incredible masthead, student contributors, and<br />

community partners. With you, our readers, let’s embark on the formidable quest<br />

to which we aspire at the Yale Scientific—to maintain objectivity without the loss of<br />

nuance, present technicality without the loss of perspective, and highlight science<br />

without the loss of humanity.<br />

About the Art<br />

Alex Dong, Editor-in-Chief<br />

Researchers have identified a<br />

pheromone that may influence the<br />

behavior of flies that spread disease<br />

in Africa. This cover illustration<br />

depicts two Tsetse flies with<br />

pheromones, represented as glowing<br />

particles, between them.<br />

Catherine Kwon, Cover Artist<br />

MASTHEAD<br />

May 2023 VOL. 96 NO. 2<br />

EDITORIAL BOARD<br />

Editor-in-Chief<br />

Managing Editors<br />

News Editor<br />

Features Editor<br />

Special Sections Editor<br />

Articles Editor<br />

Online Editors<br />

Copy Editors<br />

Scope Editors<br />

PRODUCTION & DESIGN<br />

Production Manager<br />

Layout Editors<br />

Art Editor<br />

Cover Artist<br />

Photography Editor<br />

BUSINESS<br />

Publisher<br />

Operations Managers<br />

Subscriptions Manager<br />

Outreach Manager<br />

OUTREACH<br />

Synapse Presidents<br />

Synapse Vice President<br />

Synapse Outreach Coordinators<br />

Synapse Events Coordinator<br />

WEB<br />

Web Managers<br />

Head of Social Media Team<br />

Social Media Coordinators<br />

STAFF<br />

Sanya Abbasey<br />

Luna Aguilar<br />

Ricardo Ahumada<br />

William Archacki<br />

Dinesh Bojja<br />

Risha Chakraborty<br />

Kelly Chen<br />

Leah Dayan<br />

Steven Dong<br />

Chris Esneault<br />

Erin Foley<br />

Mia Gawith<br />

Simona Hausleitner<br />

Tamasen Hayward<br />

Katherine He<br />

Miriam Huerta<br />

Sofia Jacobson<br />

Jenna Kim<br />

Catherine Kwon<br />

Charlotte Leakey<br />

Ximena Levya Peralta<br />

Yurou Liu<br />

Samantha Liu<br />

Helena Lyng-Olsen<br />

Kaley Mafong<br />

Georgio Maroun<br />

Cindy Mei<br />

Lee Ngatia Muita<br />

Lea Papa<br />

Hiren Parekh<br />

Himani Pattisam<br />

Emily Poag<br />

Madeleine Popofsky<br />

Tony Potchernikov<br />

Zara Ranglin<br />

Yusuf Rasheed<br />

Alex Roseman<br />

Ilora Roy<br />

Ignacio Ruiz-Sanchez<br />

Noora Said<br />

Alex Dong<br />

Madison Houck<br />

Sophia Li<br />

Sophia Burick<br />

Anavi Uppal<br />

Hannah Han<br />

Kayla Yup<br />

Krishna Dasari<br />

Mia Gawith<br />

Will Archacki<br />

Matthew Blair<br />

Jamie Seu<br />

Samantha Liu<br />

Anya Razmi<br />

Malia Kuo<br />

Ann-Marie Abunyewa<br />

Sydney Scott<br />

Kara Tao<br />

Catherine Kwon<br />

Jenny Wong<br />

Lucas Loman<br />

Dinara Bolat<br />

Tori Sodeinde<br />

Georgio Maroun<br />

Yusuf Rasheed<br />

Hannah Barsouk<br />

Sofia Jacobson<br />

Jessica Le<br />

Kaley Mafong<br />

Lawrence Zhao<br />

Anjali Dhanekula<br />

Abigail Jolteus<br />

Emily Shang<br />

Elizabeth Watson<br />

Keya Bajaj<br />

Eunsoo Hyun<br />

Jamie Seu<br />

Kiera Suh<br />

Yamato Takabe<br />

Joey Tan<br />

Kara Tao<br />

Connie Tian<br />

Van Anh Tran<br />

Sheel Trivedi<br />

Robin Tsai<br />

Sherry Wang<br />

Elise Wilkins<br />

Aiden Wright<br />

Elizabeth Wu<br />

Nathan Wu<br />

Johnny Yue<br />

Iffat Zarif<br />

Hanwen Zhang<br />

Lawrence Zhao<br />

Celina Zhao<br />

Matthew Zoerb<br />

The Yale Scientific Magazine (<strong>YSM</strong>) is published four times a year by Yale<br />

Scientific Publications, Inc. Third class postage paid in New Haven, CT<br />

06520. Non-profit postage permit number 01106 paid for May 19, 1927<br />

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

any submissions, solicited or unsolicited, for publication. This magazine is<br />

published by Yale College students, and Yale University is not responsible for<br />

its contents. Perspectives expressed by authors do not necessarily reflect the<br />

opinions of <strong>YSM</strong>. We retain the right to reprint contributions, both text and<br />

graphics, in future issues as well as a non-exclusive right to reproduce these<br />

in electronic form. The <strong>YSM</strong> welcomes comments and feedback. Letters to the<br />

editor should be under two hundred words and should include the author’s<br />

name and contact information. We reserve the right to edit letters before<br />

publication. Please send questions and comments to yalescientific@yale.edu.<br />

Special thanks to Yale Science and Engineering Association.


NEWS<br />

Environmental Studies / Sustainability<br />

THE CHANGING<br />

LANGUAGE OF OUR<br />

CHANGING CLIMATE<br />

HOW WORD CHOICE AFFECTS<br />

CLIMATE CHANGE PERCEPTION<br />

BY PRATIKSHA BHATTACHARYYA<br />

FREE AS A BIRD<br />

SAVING BIRDS ON<br />

YALE’S CAMPUS<br />

BY MIA GAWITH<br />

IMAGE COURTESY OF FLICKR<br />

IMAGE COURTESY OF PXFUEL<br />

Researchers from the Yale Program on Climate Change<br />

Communication (YPCCC) are using a novel method to<br />

measure public opinion on climate change—studying how<br />

people react to different phrases used to describe emissions of<br />

carbon dioxide and methane. “Over the last few decades, there<br />

has been an increased interest in the terms ‘carbon emissions’<br />

and ‘greenhouse gasses,’” said Matthew Goldberg, an author of<br />

the study and associate research scientist at the YPCCC. The<br />

team asked study participants questions about climate change,<br />

which were identical between participants apart from the specific<br />

phrase used to describe carbon emissions—either “greenhouse<br />

gas emissions,” “carbon emissions,” or “carbon pollution.”<br />

Then, the team tracked differences in responses based on<br />

the phrases used. “We were interested in getting a holistic<br />

perspective of these terms,” Goldberg said. A key finding was<br />

that different reactions to these phrases revealed more about the<br />

general associations that participants held with each term. For<br />

example, the phrases “carbon pollution” and “carbon emissions”<br />

evoked more negative reactions and correlated with a greater<br />

understanding of the environmental harms of climate change<br />

than the phrase “greenhouse gas emissions.”<br />

These insights are crucial for policymakers and<br />

environmentalists who want to effectively communicate the<br />

urgency of addressing climate change. By paying attention to how<br />

people react to the different words used to describe these crucial<br />

issues, we can gain insight into how we can best emphasize the<br />

need for action. Experts can tailor messaging to better resonate<br />

with their audience by being cognizant of widely held associations<br />

with key scientific phrases in their communication. ■<br />

We all recognize the signs: the sickening thud on a<br />

window, the flutter of feathers hitting the ground,<br />

and the stomach-churning dread of peeking outside.<br />

As one of the top causes of bird deaths, bird-window collisions<br />

kill almost one billion birds per year. However, a new project<br />

at Yale University seeks to challenge this reality: the Yale Bird-<br />

Friendly Building Initiative, a collaboration between Yale Law<br />

School’s Law, Ethics and Animals Program, the Yale Peabody<br />

Museum of Natural History, the Yale Offices of Sustainability<br />

and Facilities, and the American Bird Conservancy.<br />

Launched in the spring of 2022, the Initiative aims to<br />

mitigate bird-window collisions and adopt bird-friendly<br />

designs on Yale’s campus and beyond. The Initiative records<br />

the location, time, and cause of all reported bird deaths,<br />

preserving the bodies for future research. “If I find a dead bird<br />

or someone else brings it to me, I want to preserve it because<br />

it gives them a second life in a way, because they become<br />

imminently useful,” said Kristoff Zyskowski, collections<br />

manager at the Yale Peabody Museum. The Initiative found<br />

that designs with highly reflective, transparent glass and<br />

nearby trees create a deadly optical illusion, luring birds to<br />

their death.<br />

“Our ultimate goal, in my view, is for Yale to be the gold<br />

standard of what it looks like to be a bird-friendly campus,”<br />

said Viveca Morris, executive director of the Law, Ethics, and<br />

Animals Program. Future developments involve retrofitting<br />

Yale buildings and implementing new design regulations on<br />

campus and beyond. By saving countless birds, this project<br />

sets its sights on a new vision of wildlife sustainability. ■<br />

6 Yale Scientific Magazine May 2023 www.yalescientific.org


Physiology / Astronomy<br />

NEWS<br />

A NEW APPROACH<br />

TO AN OLD FOE<br />

INNOVATION IN AORTIC<br />

ANEUR<strong>YSM</strong> SURGERY<br />

BY JOHNNY YUE<br />

TAKING A PEEK<br />

AT PANDORA’S<br />

CLUSTER<br />

LOOKING UP AT SPACE WITH<br />

THE JAMES WEBB SPACE<br />

TELESCOPE<br />

BY IGNACIO RUIZ-SANCHEZ<br />

IMAGE COURTESY OF NAIEM NASSIRI<br />

IMAGE COURTESY OF PIXABAY<br />

Thoracoabdominal aneurysms (TAAAs) occur when the<br />

aorta—the artery carrying blood from the heart to the rest of<br />

the body—balloons and weakens, which can lead to internal<br />

bleeding. Up until the past few years, TAAA surgery required<br />

highly invasive procedures with high chances of debilitating side<br />

effects, including paraplegia, or lower body paralysis.<br />

Endovascular Debranched Aortic Repair (EDAR), a new<br />

surgical technique performed at Yale, was first invented by<br />

Patrick Kelly of Sanford Health in South Dakota. Vascular<br />

surgeon Naiem Nassiri learned about the technology under<br />

Kelly’s guidance. “I built six prototypes on my breakfast table, and<br />

some took up to six hours to build,” Nassiri said. Together with<br />

Prashanth Vallabhajosyula, director of Yale’s Aortic Institute, the<br />

medical duo has implemented EDAR to treat the weakened aorta<br />

in a minimally-invasive manner. “TAAA surgery used to involve<br />

patients getting their entire chest, abdomen, and diaphragm split<br />

open, and the procedures were attached to high morbidity and<br />

mortality,” Vallabhajosyula said.<br />

But EDAR simply involves a stent that is inserted into the<br />

body through two small penetrations made in the groin using<br />

a needle. The stent, compressed in a tube, is delivered through<br />

blood vessels to the aorta. “We’ve done about sixteen cases and<br />

haven’t encountered any paraplegia cases (patient paralysis),”<br />

Vallabhajosyula said.<br />

EDAR shows tremendous promise to treat TAAAs. “What is<br />

wonderful about this platform is that at any time, you can decide to<br />

stop the operation and bring the patient back at a later date,” Nassiri<br />

said. “This minimizes the harm for the patient.” With the surgeons’<br />

expertise, TAAA patients now have new hope for better outcomes. ■<br />

The black background of outer space is studded with<br />

white bursts of light—some are sharp lines, while others<br />

are surrounded by a white hazy glow. In the foreground<br />

sits a star from our own galaxy, shining among a giant group<br />

of galaxies located four billion light years away from Earth:<br />

Pandora’s Cluster. After the launch of NASA’s James Webb<br />

Space Telescope, we’ve been fortunate to witness images from<br />

the distant corners of our universe, but these are the first,<br />

detailed images of Pandora itself.<br />

Scientists have been monitoring this galaxy cluster for over<br />

a decade, utilizing the most advanced technology available,<br />

mainly the Hubble Space Telescope, to get a glimpse of<br />

Pandora. However, none have achieved as much as the Webb<br />

Telescope to capture stellar pictures of the cluster, unveiling<br />

never-before-seen details. The new images were a tireless effort<br />

by the Ultradeep NIRSpec and NIRCam ObserVations before<br />

the Epoch of Reionization (UNCOVER) program, whose team<br />

of astronomers included several Yale scientists. The team<br />

captured thirty hours of data using Webb’s Near-Infrared<br />

Camera (NIRcam), with wavelengths capable of detecting the<br />

earliest stars in the process of formation and nearby galaxy<br />

populations. What’s even more exciting is that the telescope<br />

captured Pandora as a megacluster, meaning the combined<br />

mass of the four galaxies creates a powerful gravitational lens<br />

to expose other very large distant galaxies in the early Universe.<br />

While strikingly beautiful, these images are not just potential<br />

dorm-room posters or lock screens—this achievement could<br />

ultimately help us discover other hidden galaxies, further<br />

unraveling the mysteries of our Universe. ■<br />

www.yalescientific.org<br />

May 2023 Yale Scientific Magazine 7


FOCUS<br />

Ecology & Evolutionary Biology<br />

SINK OR<br />

SWIM<br />

Climate change<br />

impacting fish<br />

evolution<br />

BY LEA PAPA<br />

PHOTOGRAPHY COURTESY OF PAUL-ALEXANDER LEJAS<br />

When we think about global warming, many of us<br />

imagine melting ice caps or mass extinction events,<br />

undoing the work done by millions of years of<br />

evolution. But could climate change also threaten the forward<br />

progress of evolution? A recent study investigating the role of<br />

changes in water depth in the rapid speciation, or formation<br />

of new species, of fish in polar latitudes strongly suggests that<br />

yes, global warming can affect evolution’s progress. The study<br />

specifically points to the potential negative impact of warming<br />

waters on the ability of fish to rapidly speciate and, therefore,<br />

further their evolution.<br />

Published by Yale researchers Sarah Friedman and Martha Muñoz,<br />

the paper addresses the relationship between the remarkably rapid<br />

speciation rates of fish in polar latitudes and the ability of those<br />

fish species to move through the “depth gradient”—the intervals of<br />

water depth populated by different species in a body of water.<br />

Friedman was prompted to explore this idea after reading a<br />

paper that revealed that despite the higher biodiversity among<br />

fish in tropical regions, fish in the polar regions show faster rates<br />

of speciation. This discovery was both utterly surprising and<br />

intriguing to Friedman, who worked with Muñoz—an assistant<br />

professor of Ecology and Evolutionary Biology at Yale—to pursue<br />

research that could probe this finding. “When you look at the<br />

global scale, you’re going to see more species in the tropics,”<br />

Friedman said. “But what they found was that speciation rates are<br />

actually fastest towards the poles, which is [a] really interesting<br />

and counterintuitive result.”<br />

After intensive research into the prior literature on this<br />

phenomenon, Friedman hypothesized that shifting water depth<br />

may be the mechanism for rapid fish speciation in polar latitudes.<br />

Deep waters allow fish to move across the depth gradient, isolating<br />

fish groups from each other. This separation promotes more rapid<br />

speciation than in shallow, lower latitudes, where fish are more<br />

likely to interact and reproduce, thus slowing speciation.<br />

To investigate their hypothesis, the researchers used phylogeny,<br />

a common evolutionary biology technique that visualizes the<br />

ancestry and genetic relationships between different groups<br />

through the creation and analysis of phylogenetic trees. Because<br />

of limitations caused by the COVID-19 pandemic, Friedman<br />

and Muñoz analyzed existing data on fish evolution in this metaanalytic<br />

approach to reach their conclusions about biodiversity<br />

and speciation rates in polar-region fish.<br />

By the end of their extensive research, the team’s findings<br />

supported their hypothesis. “I think it was really reassuring to<br />

find what I hypothesized to be true,” Friedman said. “Those clades<br />

that are rapidly speciating are also those ones that are moving<br />

across the depth gradient pretty rapidly as well.” The relationship<br />

between rapid speciation rates and the ability to traverse a wider<br />

depth gradient explained the surprising speciation rates in the<br />

polar latitudes.<br />

Friedman and Muñoz also consider other findings from their<br />

study to be particularly intriguing, including one that suggested<br />

a pipeline of biodiversity exchange across latitudes, particularly<br />

from polar to tropical latitudes. “In fact, what we discovered is that<br />

speciation is faster at the poles, reflecting greater depth transitions,<br />

and that diversity is later transported to the tropics, so the polar<br />

regions are actually supplying species to the tropics,” Muñoz said.<br />

What could these findings mean for biodiversity and speciation<br />

in the era of extreme climate change and warming waters?<br />

According to Dr. Friedman, the effects will be disastrous. Because<br />

of the constant cold of the poles, there is little difference in water<br />

temperature throughout the depth gradient, meaning that the fish<br />

species through the gradient in the poles are similarly adapted<br />

for temperature, which contributes to how easily polar fish move<br />

between shallow and deep water. “As temperatures, and especially<br />

those surface temperatures, start warming up due to global<br />

warming, it’s going to increase the barriers to moving along that<br />

gradient,” Friedman said.<br />

Could global warming stall evolution? According to the<br />

researchers, this may be an extreme conclusion. Nevertheless,<br />

their research opens our eyes to a previously unknown harm of<br />

climate change, re-emphasizing the need for meaningful action. ■<br />

8 Yale Scientific Magazine May 2023 www.yalescientific.org


Computer Science<br />

FOCUS<br />

TEACHING<br />

MACHINE<br />

LEARNING<br />

PHOTOGRAPHY COURTESY OF PAUL-ALEXANDER LEJAS<br />

Machine learning is often thought of as the silver bullet<br />

for solving puzzles in science. With enough data in<br />

any given subject, a model with impressive predictive<br />

properties can be created to produce an abundance of helpful<br />

information. But sometimes, machine learning isn’t perfect. In their<br />

recent paper, Guannan Liu and his colleagues at the Schroers Lab<br />

at Yale explore the limitations of machine learning models and how<br />

we can incorporate human learning into new models to strengthen<br />

their predictive power.<br />

Liu, a Ph.D. candidate in Mechanical Engineering and Materials<br />

Science, has spent most of his time at Yale studying machine learning<br />

and its ability to solve complex materials science problems. The<br />

study of glass-forming ability is a canonical example of one of these<br />

problems. It is quantified by the minimum cooling rate required to<br />

prevent the formation of undesired crystalline structures, resulting<br />

in a glass with an amorphous atomic structure. Studying glassforming<br />

ability by performing hands-on experiments in the lab<br />

can be tedious, and this is where machine learning comes in to<br />

potentially accelerate the process. “Simply put, machine learning is<br />

trying to make inferences from data, and maybe predict something<br />

from [that] data,” Liu said.<br />

But there’s a catch—previous machine learning models designed<br />

to predict the glass-forming ability of metallic glasses have fallen<br />

short of providing useful insights on the subject. Metallic glasses<br />

are alloys, which are made by combining two or more elements.<br />

“You have to have meaningful features that describe the particular<br />

alloy after the mixing of elements,” Liu said. Liu contextualized this<br />

idea by offering an example. “For atomic size, it’s not the average<br />

[element size] that matters but the difference in size,” Liu said.<br />

“This allows space to be filled as much as possible, favorable for<br />

glass formation.” Models that lack such information and instead<br />

arbitrarily use statistical functions to construct features do not truly<br />

capture the essence of the alloy’s glass-forming ability.<br />

The other issue with the previous machine learning model for<br />

the glass-forming ability of alloys was its limited capacity to make<br />

new predictions. “[In] the previous model, usually the task was<br />

interpolation—the model was only predicting things that were<br />

www.yalescientific.org<br />

Improving a machine learning<br />

model to better predict<br />

metallic glass formation<br />

BY MAYA KHURANA<br />

similar to the dataset,” Liu said. In other words, the model could not<br />

make any predictions for new and unfamiliar data—it could only<br />

work inside the bounds of the dataset.<br />

To rectify these errors, Liu and his team worked on a new machine<br />

learning model: one that incorporated scientific insights from<br />

human learning. “Our model used extrapolation, [or] prediction<br />

into unknown space,” Liu said. This way, they were able to align their<br />

machine learning model with the reality that they have observed in<br />

the lab. Take, for instance, the property of atomic size again. Larger<br />

differences in size result in better glass-forming ability because the<br />

atoms are able to pack in more tightly. It is properties such as these<br />

that Liu and his team were better able to account for in their model,<br />

and their approach worked. “We found that our model was actually<br />

very successful in predicting glass-forming ability,” Liu said.<br />

Unlike its predecessors, this model was much better at<br />

extrapolation. “Our model can predict alloys that are more distinct<br />

from the training set,” Liu said. “We concluded that physical insights<br />

are really needed [to develop effective machine learning models].”<br />

This project is far from the end of Liu’s work with machine<br />

learning for materials science. He has three main goals moving<br />

forward. “The first is to use machine learning to test [our] current<br />

understanding of complex material science problems,” Liu said. It<br />

can be hard to quantify the efficacy of foundational rules within<br />

material science, so Liu plans to use machine learning to evaluate<br />

these guiding principles. Secondly, Liu strives to combine machine<br />

learning and high-throughput fabrication methods to discover<br />

new metallic glasses.<br />

Finally, Liu will investigate the contexts in which machine<br />

learning can be helpful. His goal is to determine what kinds of<br />

problems it can help solve and what circumstances limit its utility.<br />

“[We want to] have a viewpoint that can be meaningful for the<br />

community as to what machine learning is useful for [versus]<br />

situations where machine learning would be hard to use,” Liu said.<br />

This research will ensure that machine learning models are taking<br />

all possible human insights into account while making inferences<br />

from data. Clearly, machine learning can be an extremely valuable<br />

tool if it is wielded skillfully. ■<br />

May 2023 Yale Scientific Magazine 9


FOCUS<br />

Biomedical Engineering<br />

A DYNAMIC<br />

DUO<br />

Combining two<br />

technologies to fight<br />

brain cancer<br />

BY CASEY MCGUIRE<br />

PHOTOGRAPHY COURTESY OF YAZHE WANG<br />

It’s a diagnosis that strikes fear in the hearts of patients and their<br />

loved ones: glioblastoma, a type of brain cancer that is notoriously<br />

aggressive and difficult to treat. However, hope may be on the<br />

horizon, as researchers from Yale and the University of Connecticut<br />

(UConn) have developed a groundbreaking new therapeutic approach<br />

for those battling this devastating disease. The treatment loads tiny<br />

particles called nanoparticles, developed by Professor Mark Saltzman’s<br />

lab at Yale, with proteins that target the tumor cells, designed by<br />

Professor Raman Bahal and his team at UConn. Currently, the best<br />

treatment for glioblastoma is the removal of the bulk of the tumor<br />

during surgery, followed by radiation and chemotherapy. However, the<br />

median survival is only fifteen months. This new treatment combines<br />

two cutting-edge technologies, nanoparticles and peptide nucleic<br />

acids, to tackle this lethal disease and provide hope for future patients.<br />

Nanoparticles are particles that can infiltrate cells due to their small<br />

size. Saltzman’s lab has extensively researched nanoparticles as a vehicle<br />

to deliver drugs to specific areas of the human body. The polymerbased<br />

nanoparticle developed by his team can penetrate the brain<br />

and reach the tumor cells. Saltzman underlined the importance of the<br />

nanoparticles remaining at the tumor site and continuing to deliver<br />

the drug over time. “You can only administer the therapy after surgery<br />

directly into the brain and you cannot re-administer, but we want the<br />

therapy to last a long time,” Saltzman said. “We designed nanoparticles<br />

with certain properties to allow for this behavior.” The particles have<br />

an affinity for tumor cells due to their bioadhesive coating, and they<br />

will stick around to slowly release the drug inside the cells.<br />

The drugs encapsulated in the nanoparticles were designed<br />

by Bahal, who was a postdoctoral researcher and collaborator of<br />

Saltzman’s at Yale before moving to UConn. Bahal’s team developed<br />

peptide nucleic acids, or PNAs, to be loaded inside the nanoparticles.<br />

These proteins are synthetically constructed to be complementary<br />

to a certain sequence of microRNA, or short strands of RNA that<br />

regulate gene expression in cells. The tumor cells of glioblastomas<br />

overexpress certain microRNAs, leading to more tumor growth<br />

and decreased patient survival. Past studies suggest that two of<br />

these upregulated microRNAs, miR-10b and miR-21, are the most<br />

significant in glioblastomas. These microRNAs have been shown<br />

to exacerbate tumor growth and invasion, while decreasing the<br />

effectiveness of Temozolomide, the type of chemotherapy typically<br />

used for glioblastomas. The researchers loaded a mixture of the PNAs<br />

against miR-10b and miR-21 into the nanoparticles.<br />

After surgery, this treatment can be administered directly into<br />

the brain to target the remaining cancerous cells. Therefore, this<br />

treatment would be an addition to the current standard of care.<br />

During mouse trials, this therapy improved survival and also<br />

enhanced the efficacy of the chemotherapy. “The results are very<br />

promising, and I think there is an opportunity here,” Saltzman said.<br />

He described how the researchers are striving to move towards more<br />

extensive safety testing and eventually clinical trials.<br />

Glioblastomas account for just a fraction of cancer patients. In<br />

2022, brain and other nervous system cancers added up to 1.3<br />

percent of cancer cases in the United States, and 14.5 percent of<br />

these nervous system tumors were glioblastomas. Despite this<br />

seemingly low percentage, Saltzman has researched drug delivery<br />

systems for glioblastomas for around thirty-five years and defends<br />

its importance as a focus of research. “It’s rare, but not as rare as you<br />

would think,” Saltzman said. Even though his results were published<br />

in early February in Science Advances, he still receives one or two<br />

emails a day from people searching for new treatments for a family<br />

member suffering from a glioblastoma. Saltzman’s driving force for<br />

his glioblastoma research and this project is the hope it provides<br />

for patients. “I’ve become fascinated with this challenge and want<br />

to do something that really helps people,” Saltzman said. “Along the<br />

way, I have met a lot of individuals with glioblastoma. They are not<br />

alive anymore and that has had a huge impact on me. It feels more<br />

like a mission now than just an interesting project to work on.”<br />

Saltzman’s nanoparticles loaded with PNAs present a novel<br />

and precise approach to address the currently inadequate<br />

landscape of therapeutic options for glioblastoma. When<br />

integrated into the standard of care, this dynamic duo has the<br />

potential to improve survival rates, finally giving glioblastoma<br />

patients a fighting chance. ■<br />

10 Yale Scientific Magazine May 2023 www.yalescientific.org


Environmental Science<br />

FOCUS<br />

THE CARBON<br />

FOOTPRINT<br />

OF CARE<br />

The unexpected<br />

environmental impacts<br />

of prostate biopsies<br />

BY JESSICA LE<br />

IMAGE COURTESY OF WIKIMEDIA COMMONS<br />

When someone is planning to get a prostate biopsy—<br />

the main diagnostic test for prostate cancer—the<br />

environmental impact of their impending procedure<br />

is not usually at the forefront of their mind. However, a Yale-led<br />

study by Associate Professor of Urology Michael Leapman did just<br />

that: the team examined the environmental impacts of common<br />

screening methods like prostate magnetic resonance imaging<br />

(MRI) and prostate cancer procedures, estimating that a single<br />

transrectal prostate biopsy has the same CO 2 emissions as a roundtrip<br />

flight from New York to San Francisco.<br />

On a global scale, healthcare systems are a major source of<br />

pollution and constitute over four percent of global CO 2 emissions.<br />

Although the environmental impacts of medical procedures<br />

are not currently considered when making medical decisions,<br />

Leapman urges for a change in attitude within the medical industry<br />

to prioritize environmental stewardship that aligns with patient<br />

interest without compromising patient care. “Carbon impact comes<br />

into question when we have excessive medical care,” Leapman said.<br />

Unnecessary over-screening is a common occurrence, and<br />

invasive procedures such as prostate biopsies actually have the<br />

potential to harm certain patients. As early as fifty years old, men are<br />

advised to consider undergoing a biopsy screening to catch prostate<br />

cancer in its early stages. Overall, these procedures are shown to<br />

reduce death rates; however, for patients who are over seventy or<br />

have existing comorbidities, this invasive diagnostic procedure<br />

would risk unwarranted side effects, major hospitalization, or even<br />

death. This form of medical care is often considered low-value and<br />

may harm both the planet and the patient.<br />

“The story is more than just the carbon footprint of one<br />

procedure. It is also about making better healthcare decisions that<br />

equip patients and physicians with more reliable information for<br />

who might need what intervention,” Leapman said. Approximately<br />

one million prostate biopsies are performed per year in the United<br />

States alone, with more than half of the patients evaluated found to<br />

not have prostate cancer at all. His research found that performing<br />

one hundred thousand fewer biopsies would avoid over eight<br />

www.yalescientific.org<br />

million kilograms of CO 2 emission, the equivalent of burning 1.1<br />

million gallons of gasoline (larger procedures, such as surgeries,<br />

may easily account for more than ten times that amount).<br />

However, this issue addresses a broader problem facing healthcare<br />

management. Leapman noted that physicians are not proactive in<br />

considering the economic burden, much less the environmental<br />

burden, of expensive procedures. Introducing carbon footprint<br />

as a price to be considered when making important medical<br />

decisions should be implemented in a holistic conversation around<br />

when exactly to prescribe medical treatment. This ensures that the<br />

patient understands the broader benefits and risks of undergoing<br />

an expensive procedure, encouraging physicians and patients to be<br />

more considerate of both economic and environmental costs.<br />

Leapman emphasizes that global climate change directly<br />

influences public health. “Healthcare providers are not doing a<br />

good job if what we are doing hurts the community and our world,”<br />

Leapman said. However, the movement towards environmentally<br />

friendly healthcare is not easy and faces many barriers to<br />

progress. Leapman’s study found that energy expenditure is the<br />

largest contributor to the overall carbon footprint calculation<br />

(approximately forty percent). In general, hospitals require an<br />

immense amount of resources and energy. However, they work<br />

within a very thin financial margin for extra expenses, making<br />

it difficult for individual practitioners and hospitals to prioritize<br />

advocating for greener energy sources. “Federal regulation and<br />

oversight may need to come in if our overall goal is to improve<br />

public health,” Leapman said. “We need to make some hard<br />

decisions about the resources we allocate to ensure we are being<br />

good stewards of the environment.”<br />

Leapman hopes that generating more data to clearly illustrate the<br />

environmental impact of healthcare will help increase awareness<br />

and target areas of excessive medical care. By doing so, necessary<br />

modifications can be made to decrease superfluous resource<br />

use. Then, doctors can make better decisions when choosing<br />

appropriate patients to undergo certain procedures, in the interest<br />

of both the patient and the planet. ■<br />

May 2023 Yale Scientific Magazine 11


FOCUS<br />

Geochemistry<br />

TRACKING CARBON’S<br />

UNDERWATER<br />

DIVE<br />

ART BY LUNA AGUILAR<br />

Clearing up the history of the<br />

marine carbonate cycle<br />

BY TORI SODEINDE<br />

Carbon: it’s in the atmosphere, the<br />

oceans, the solid Earth, and even in us.<br />

This element is found all throughout<br />

Earth’s environment and exists in numerous<br />

chemical forms. One form of carbon, calcium<br />

carbonate (the major component of limestone<br />

and chalk), is the main form in which carbon<br />

in the ocean and atmosphere is returned<br />

to the earth. The precipitation pathways of<br />

carbonate minerals in the ocean are referred<br />

to as the marine carbonate factory and greatly<br />

influences abiotic and biotic geochemistry,<br />

including ocean acidity.<br />

Despite its important role in ocean<br />

chemistry, there has been little consensus<br />

on how the marine carbonate factory has<br />

changed throughout Earth’s history. It is<br />

challenging to<br />

find wellpreserved<br />

and reliable markers for its status<br />

over billions of years. However, Lidya Tarhan,<br />

an assistant professor of earth and planetary<br />

sciences, and Jiyuan Wang, an Agouron<br />

postdoctoral fellow in Tarhan’s research<br />

group, along with colleagues from Yale’s<br />

Department of Earth and Planetary Sciences,<br />

Northwestern University and University of<br />

Miami, recently developed a novel technique<br />

to trace the history of the marine carbonate<br />

factory. By measuring the ratios of different<br />

isotopes (atoms of the same element with<br />

different masses) of strontium within<br />

carbonate samples, they uncovered a more<br />

definitive history of carbonate precipitation<br />

and mineral saturation states from the ancient<br />

Precambrian to the recent Phanerozoic<br />

Eon, and published their findings in Nature.<br />

During the Precambrian, contrary to previous<br />

conjecture, a major proportion of carbonate<br />

was buried in the deep sea through abiotic<br />

processes, rather than in the shallow marine<br />

environment like reefs that dominate most of<br />

the Phanerozoic marine carbonate factory.<br />

The Marine Carbonate Cycle<br />

The marine carbonate factory is one piece<br />

of a bigger puzzle, the carbon cycle, which<br />

encompasses the cycling of carbon through<br />

nature. The carbon cycle can be divided into<br />

short-term and long-term cycles. The shortterm<br />

carbon cycle involves living organisms.<br />

Photosynthesizers, largely phytoplankton<br />

and algae, absorb carbon dioxide into their<br />

cells and use it to generate carbohydrates<br />

through photosynthesis. The carbohydrates<br />

can be broken down later to provide energy,<br />

releasing carbon dioxide back into the ocean<br />

and atmosphere.<br />

In the long-term carbon cycle, rain<br />

combines with atmospheric carbon dioxide<br />

to form carbonic acid, which falls to the earth<br />

and slowly dissolves bodies of rock. This<br />

releases ions, including calcium, that are then<br />

carried through rivers to the ocean, where they<br />

combine with dissolved carbonate ions to form<br />

calcium carbonate, a solid in water. This process<br />

is called carbonate precipitation and can occur<br />

abiotically (without living organisms).<br />

However, many marine organisms also use<br />

calcium and carbonate ions to build their<br />

shells. When they die, these shells and other<br />

sediments form rock, sequestering carbon<br />

within the ocean floor and the geologic<br />

record. Some bacteria can also facilitate<br />

precipitation of calcium carbonate in their<br />

surroundings—for instance, by taking up<br />

12 Yale Scientific Magazine May 2023 www.yalescientific.org


Geochemistry<br />

FOCUS<br />

carbon dioxide during photosynthesis.<br />

Regardless of the route, precipitation of<br />

dissolved carbonate into solid calcium<br />

carbonate incorporates other ions including<br />

strontium, an alkaline earth metal. This study<br />

exploited the incorporation of strontium into<br />

carbonate precipitates to gain insight into the<br />

history of the marine carbonate cycle.<br />

Strontium in the Marine Carbonate<br />

Factory's History<br />

The metal strontium has multiple stable<br />

isotopes, including strontium-88 and<br />

strontium-86. When carbonate precipitation<br />

occurs in the ocean, it incorporates trace<br />

amounts of strontium, but the two isotopes<br />

are incorporated at different ratios depending<br />

on environmental conditions. Strontium-88,<br />

the heavier isotope, is incorporated into<br />

carbonate minerals less often than the lighter<br />

strontium-86, but higher saturation of<br />

carbonates in the ocean leads to both faster<br />

precipitation and an even lower strontium-88<br />

to strontium-86 ratio (δ 88/86 Sr) in carbonates.<br />

The ratio of these strontium isotopes in<br />

carbonates, in particular, is a novel proxy<br />

for the history of the marine carbonate<br />

cycle because this signature is tied closely to<br />

precipitation rates, rather than—like many<br />

other isotope systems—seawater temperature<br />

or the type of carbonate mineral in which<br />

strontium is incorporated. Thus, strontium<br />

stable isotope ratios can serve as a marker<br />

for changes in the marine carbonate factory,<br />

specifically the rate of carbonate precipitation<br />

which, in turn, reflects marine carbonate<br />

saturation state at the time of precipitation.<br />

However, using stable isotope measurements<br />

has not previously been possible due to<br />

technical limitations. Luckily, with the<br />

resources of the Yale Metal Geochemistry<br />

Center, the researchers were able to develop<br />

a novel method using mass spectrometry to<br />

measure stable strontium isotope ratios with<br />

five-decimal place precision, according to<br />

Wang. “[Our work] opened the door toward<br />

using the stable strontium isotope proxy to<br />

reconstruct long-term records in Earth's<br />

history—and will, we hope, allow us and others<br />

to tackle new and exciting questions down the<br />

road,” Tarhan said.<br />

Unexpected Sources of Carbonate<br />

Precipitation<br />

While shallow regions of the ocean like<br />

reefs and carbonate platforms are commonly<br />

www.yalescientific.org<br />

thought of as hotspots for carbon deposition,<br />

which is true today, Tarhan and Wang found<br />

an unexpected phenomenon during the<br />

Precambrian, the interval preceding the<br />

explosion of organisms that created calcium<br />

carbonate shells around 540 million years<br />

ago. They found evidence of an unforeseen<br />

level of abiotic contribution to the marine<br />

carbonate cycle in deep ocean waters<br />

during this time. “A major part of carbonate<br />

was buried outside of the shallow marine<br />

environment during Earth’s early history,<br />

which is radically different than previously<br />

envisaged,” Wang said.<br />

When tracing the ratios of strontium<br />

isotopes in carbonate samples formed in<br />

shallow seafloor sediments, the researchers<br />

found a marked decrease in δ 88/86 Sr<br />

values during the transition between the<br />

Precambrian era and the Phanerozoic era (the<br />

interval in which biomineralizing animals<br />

caused skeletal carbonates to become a large<br />

contributor to the marine carbonate factory).<br />

This decrease implies slower precipitation<br />

and a lower carbonate saturation state in<br />

Phanerozoic relative to Precambrian oceans,<br />

which is consistent with the increase in<br />

precipitation due to calcifying animals in the<br />

Phanerozoic period.<br />

Additionally, the Precambrian δ 88/86 Sr<br />

record also suggests the unexpected presence<br />

of a large, non-skeletal carbonate sink within<br />

the Precambrian deep ocean—one formed<br />

as a result of the activities of bacteria living<br />

in seafloor sediments devoid of oxygen. This<br />

condition was likely characteristic of much<br />

of the Precambrian deep seafloor, leading to<br />

carbonate precipitation in the spaces between<br />

grains of previously deposited sediment.<br />

It is difficult to directly confirm the ancient<br />

history of the deep oceans, as the constant<br />

shifting of Earth’s tectonic plates leads to<br />

subduction, plates layering over each other on<br />

the deep seafloor, which would have contained<br />

this missing piece of the Precambrian<br />

ABOUT THE AUTHOR<br />

carbonate record. “The deep oceans have been<br />

something of a 'black box' for much of Earth's<br />

history, due to the continual loss of deep-sea<br />

sediments with seafloor subduction,” Tarhan<br />

said. However, this study has unveiled an<br />

aspect of this murky history. “The deep sea,<br />

among other muddy stretches of the ancient<br />

seafloor, may have been an important locus of<br />

carbonate sediment accumulation prior to the<br />

emergence of any carbonate-biomineralizing<br />

organisms, and this was the baseline state<br />

until biomineralizing animals evolved in the<br />

shallow oceans approximately 540 million<br />

years ago,” Tarhan said.<br />

Looking into the Future<br />

This new research challenges past<br />

assumptions about the main players in the<br />

marine carbonate factory and helps fill in the<br />

history of oceanic geochemistry prior to the<br />

evolution of marine calcifying animals. This<br />

research could also be used to predict the<br />

future. As humans continue to pump carbon<br />

dioxide into the atmosphere, the increased<br />

emissions alter the natural carbon cycle.<br />

While this study focused on Earth’s ancient<br />

history, the mechanisms underlying the<br />

carbon cycle remain the same, so clarifying<br />

the mechanism of past changes can help us<br />

extrapolate how human actions may now<br />

affect the carbon cycle.<br />

Tarhan’s lab is currently trying to<br />

quantify the behavior of strontium isotopes<br />

as it relates to changing seawater carbonate<br />

chemistry under ongoing climate change.<br />

“The discoveries in this study enable us<br />

to better understand how carbon cycled<br />

among Earth’s different layers and how<br />

Earth maintained its habitability under<br />

different levels of CO 2 ,” Wang said. “This<br />

is crucial information that can be used to<br />

perceive and predict the behaviors of our<br />

Earth and oceans [during] contemporary<br />

climate change.” ■<br />

TORI SODEINDE<br />

TORI SODEINDE is a sophomore MCDB major in Ezra Stiles College. In addition to writing for <strong>YSM</strong>, she<br />

is involved in telomere biology research, Danceworks, and the Downtown Evening Soup Kitchen.<br />

THE AUTHOR WOULD LIKE TO THANK Dr. Lidya Tarhan and Dr. Jiuyuan Wang for their time and<br />

enthusiasm about their research.<br />

REFERENCES:<br />

Wang, J., Tarhan, L.G., Jacobson, A.D. et al. The evolution of the marine carbonate factory. Nature 615,<br />

265–269 (2023). https://doi.org/10.1038/s41586-022-05654-5<br />

May 2023 Yale Scientific Magazine 13


FOCUS<br />

Medicine<br />

IT'S IN OUR<br />

BON<br />

E S<br />

THE LINK BETWEEN AGING<br />

AND ATHEROSCLEROSIS<br />

BY EVELYN JIANG | ART BY GIA GABRAL<br />

They lurk in your arteries, plaques that<br />

build up like hidden time bombs.<br />

These tiny fatty deposits can slowly yet<br />

steadily narrow your blood vessels, causing<br />

potentially life-threatening complications.<br />

Atherosclerosis, as it’s medically known,<br />

is a complex and often silent disease.<br />

Despite its lack of obvious warning<br />

signs, atherosclerosis is the leading<br />

cause of heart attacks, strokes, and other<br />

cardiovascular complications, which are<br />

collectively the leading cause of death<br />

worldwide. The deadly disease has earned<br />

itself the nickname the ‘silent killer’ and its<br />

prevalence has made it a central focus in<br />

cardiovascular research.<br />

Aging is the biggest risk factor for<br />

developing atherosclerosis, but the<br />

reasons for this observation have been<br />

a longstanding mystery for scientists. A<br />

team of researchers in the Greif Lab at<br />

the Yale School of Medicine has recently<br />

uncovered a crucial link between bone<br />

marrow aging and atherosclerosis that may<br />

offer part of the answer. By examining the<br />

role of bone marrow cells in the clonality<br />

of smooth muscle cells, the researchers<br />

pinpointed key molecular mechanisms<br />

that contribute to atherosclerosis.<br />

Born From Bone Marrow<br />

Smooth muscle is a type of muscle found<br />

in the walls of many organs and tissues in the<br />

body. It is called ‘smooth’ because smooth<br />

muscle cells (SMCs) lack the striations or<br />

visible bands characteristic of skeletal and<br />

cardiac muscle cells. SMCs have a spindleshaped<br />

appearance and are not under<br />

voluntary control like skeletal muscle<br />

cells. Instead, they are controlled by the<br />

autonomic nervous system and hormones.<br />

SMCs are responsible for maintaining the<br />

structural integrity of the arterial wall, but<br />

research has shown that only a select few<br />

SMCs also play a significant role in the<br />

development of atherosclerosis.<br />

When a plaque begins to form,<br />

macrophages—a type of white blood cell—<br />

are the first to arrive on the scene. They engulf<br />

oxidized low-density lipoprotein and form<br />

foam cells that, over time, accumulate to form<br />

fatty streaks and eventually develop into fullfledged<br />

plaques. Macrophages also release<br />

pro-inflammatory cytokines, chemicals that<br />

attract more immune cells, that contribute<br />

to plaque growth. Later on, rare SMCs arrive<br />

and initially attach themselves to the surface<br />

or cap of the plaque, proliferate robustly, and<br />

migrate to cover this fibrous cap. Some of the<br />

SMCs then dive into the core of the plaque.<br />

The cap stabilizes the plaque, protecting it<br />

from rupturing; if the cap becomes weak and<br />

ruptures, the contents of the plaque core are<br />

exposed to the bloodstream, triggering the<br />

formation of a clot. “When a clot blocks the<br />

artery, then blood can’t get beyond it, and the<br />

tissue that’s beyond it doesn’t get oxygen,”<br />

said Daniel Greif, professor of cardiology at<br />

the Yale School of Medicine and principal<br />

investigator. “That’s what causes the vast<br />

majority of heart attacks and strokes.”<br />

Even though up to seventy percent of cells<br />

in advanced plaques originate from SMCs,<br />

they originate from only one or a couple<br />

of SMCs that enter the plaque. In younger<br />

mice that are prone to atherosclerosis, the<br />

SMCs that contribute to plaque formation<br />

are clonally related, or monoclonal, meaning<br />

they originate from a single cell that entered<br />

the plaque. However, with aging, the number<br />

of monoclonal plaques decreases, and<br />

there is an increase in polyclonal plaques,<br />

where multiple SMCs contribute to plaque<br />

formation. Polyclonality creates a more<br />

genetically diverse and perhaps unstable<br />

population of cells that can lead to aggressive<br />

plaque formation, thereby increasing both<br />

the size of the plaque and the risk of rupture.<br />

How Does Age Impact Clonality?<br />

To study the connection between SMC<br />

clonality and aging, the research team<br />

14 Yale Scientific Magazine May 2023 www.yalescientific.org


Medicine<br />

FOCUS<br />

PHOTOGRAPH COURTESY OF THOMAS R. SHARKEY.<br />

Atherosclerosis is a disease in which plaque builds up inside the arteries, leading to a narrowing and hardening<br />

of the arteries, which can restrict blood flow.<br />

compared atherosclerotic plaques of aged<br />

and young mice. The mice carried the<br />

ROSA26R-Rainbow (Rb) Cre reporter,<br />

which is used to label cells with different<br />

fluorescent colors, allowing the researchers<br />

to track the clonal expansion of cells.<br />

Sections of aortas from the mice were<br />

stained and imaged for Rb colors, and<br />

analysis revealed that aged mice had larger<br />

plaques with increased SMC polyclonality<br />

and lipid content, implying an increased<br />

risk of plaque rupture.<br />

The researchers then transplanted bone<br />

marrow from aged mice into young mice<br />

genetically engineered to be prone to<br />

atherosclerosis to see if aged bone marrow<br />

was sufficient to induce polyclonality.<br />

They found that the mice that received<br />

the aged bone marrow transplant<br />

developed greater plaque buildup in their<br />

arteries and that their plaques exhibited<br />

increased SMC polyclonality. They also<br />

found that when liquid from cultures of<br />

macrophages of aged mice was incubated<br />

with aortic SMCs from young mice,<br />

SMC proliferation increased by about<br />

threefold, compared to incubation with<br />

the liquid from macrophage cultures of<br />

young mice. These results suggest that<br />

the age of the bone marrow, specifically<br />

the age of macrophages, is a key factor in<br />

determining the recruitment and clonality<br />

of SMC-derived plaque cells.<br />

The Molecular Mechanisms<br />

The researchers next sought to explain<br />

the molecular mechanisms underlying<br />

aging’s observed effect on how SMCs were<br />

recruited and expanded in the plaque. To do<br />

so, they isolated monocytes—precursors to<br />

macrophages—from a blood draw of young<br />

and aged humans and from the bone marrow<br />

of young and aged mice, then performed<br />

RNA and protein analysis on them. They<br />

found that a gene called integrin β3—which<br />

is essential for blood clot formation—<br />

was downregulated in aged monocytes.<br />

Decreased integrin β3 levels in mice were<br />

found to contribute to atherosclerosis.<br />

Single-cell RNA sequencing of bone<br />

marrow cells from mice with or without<br />

integrin β3 revealed that the absence of<br />

ABOUT THE AUTHOR<br />

integrin β3 leads to the upregulation of<br />

pro-inflammatory tumor necrosis factor α<br />

(TNFα) signaling pathways, and inhibition<br />

of TNFα led to a reduction of over fifty<br />

percent of SMC-derived plaque cells. It<br />

also promoted monoclonality, suggesting<br />

that integrin β3 deficiency promotes<br />

atherosclerotic plaque development by<br />

inducing inflammation through the TNFα<br />

signaling pathway. This inflammation<br />

further damages the artery walls, triggering<br />

the recruitment of more macrophages to<br />

the site and therefore the formation of more<br />

fatty streaks. Inflammatory molecules can<br />

also stimulate the proliferation of SMCs<br />

and weaken fibrous caps of plaques, making<br />

them more likely to burst.<br />

The researchers also showed that<br />

overexpression of integrin β3 in the bone<br />

marrow of aged mice led to predominantly<br />

monoclonal SMC populations and reduced<br />

the amount of plaque buildup within<br />

arteries. By increasing the levels of integrin<br />

β3, the researchers were able to prevent<br />

the recruitment and expansion of multiple<br />

SMC progenitors into the plaque, resulting<br />

in a reduced risk of plaque rupture.<br />

The study was led by Inamul Kabir, an<br />

associate research scientist in the Greif Lab.<br />

"It is gratifying to uncover the molecular<br />

mechanism of atherosclerotic disease<br />

progression at the cellular level during aging,<br />

thus informing potential novel therapy,”<br />

Kabir said. The team’s research revealed<br />

the previously unknown mechanisms<br />

of how aged macrophages induce SMC<br />

polyclonality and the development of fatty<br />

plaques in the arteries. This breakthrough<br />

marks the start of a long journey toward<br />

effective treatments for atherosclerosis.<br />

Nonetheless, these new findings represent a<br />

notable milestone in our understanding of<br />

the ‘silent killer.’ ■<br />

EVELYN JIANG<br />

EVELYN JIANG is a first-year in Morse College interested in studying neuroscience. In addition<br />

to writing for the <strong>YSM</strong>, she works at Yale’s Alzheimer’s Disease Research Unit and plays with<br />

proteins at the Koleske Lab.<br />

THE AUTHOR WOULD LIKE TO THANK Daniel Greif and Inamul Kabir for their time and<br />

enthusiasm in sharing their research.<br />

REFERENCES:<br />

Kabir, I., Zhang, X., Dave, J.M. et al. The age of bone marrow dictates the clonality of smooth<br />

muscle-derived cells in atherosclerotic plaques. Nat Aging 3, 64–81 (2023). https://doi.<br />

org/10.1038/s43587-022-00342-5<br />

www.yalescientific.org<br />

May 2023 Yale Scientific Magazine 15


FOCUS<br />

Dermatology<br />

ACNE-BIOTICS<br />

Demystifying a promising<br />

acne-fighting antibiotic<br />

BY CRYSTAL LIU<br />

ART BY HANNAH HAN<br />

16 Yale Scientific Magazine May 2023 www.yalescientific.org


Dermatology<br />

FOCUS<br />

Bumps, whiteheads, rashes, scars: acne<br />

vulgaris is the most prevalent skin<br />

disease in the world, affecting the<br />

physical and mental health of 9.4 percent of<br />

the global population. This figure includes<br />

a whopping eighty-five percent of people<br />

between twelve and twenty-four years old.<br />

Cutibacterium acnes is the major cause<br />

of acne. It is a Gram-positive bacterium,<br />

meaning it has a thicker cell wall and causes<br />

different infections than Gram-negative<br />

bacteria. C. acnes coexists with healthy skin<br />

follicles and pores, but certain strains lead<br />

to acne and other complications, such as<br />

eye inflammation after tissue implantation.<br />

To treat these infections, dermatologists<br />

often prescribe a class of antibiotics called<br />

“tetracycline,” which include doxycycline,<br />

minocycline, and sarecycline.<br />

Tetracycline-class antibiotics are a group<br />

of medications used in the treatment of<br />

bacterial infectious diseases. They target<br />

the ribosome, an organelle that translates<br />

genetic information from RNA sequences<br />

into amino acid chains, which then fold into<br />

proteins. Tetracycline is a naturally-occurring<br />

antibiotic isolated from actinomycetes, a<br />

soil bacteria, and was approved by the FDA<br />

for medical use in 1954. Doxycycline and<br />

minocycline, termed second-generation<br />

tetracyclines, were approved in 1967<br />

and 1971, respectively, thanks to their<br />

improved stability and pharmacological<br />

efficacy. Almost half a century later, in<br />

2018, sarecycline was introduced as a thirdgeneration<br />

tetracycline-class antibiotic.<br />

While doxycycline and minocycline kill<br />

all types of bacteria—meaning they are<br />

broad-spectrum antibiotics—sarecycline has<br />

narrow-spectrum activity against only certain<br />

Gram-positive bacteria, including C. acnes.<br />

Christopher Bunick, associate professor<br />

of dermatology at the Yale School of<br />

Medicine, noticed the importance of this<br />

novel antibiotic and decided to look into<br />

its molecular mechanism. “Because of our<br />

expertise in protein synthesis, ribosome<br />

structure, and dermatology, we couldn’t<br />

resist taking on this project,” said Ivan<br />

Lomakin, an associate research scientist in<br />

the Bunick lab. Lomakin, Bunick, and their<br />

collaborators analyzed how sarecycline<br />

interacts with the C. acnes ribosome using<br />

cryogenic electron microscopy (cryo-EM),<br />

and published the results in Nucleic Acids<br />

Research. They discovered that sarecycline<br />

binds to the C. acnes ribosome at two<br />

different sites, which had not been observed<br />

in structures with other tetracyclines or<br />

model bacteria. They also discovered two<br />

novel ribosomal proteins and demonstrated<br />

their antimicrobial properties independent<br />

of the ribosomal complex. This study<br />

ultimately confirmed that sarecycline may<br />

be a more effective treatment option for C.<br />

acnes infections.<br />

Why Bind To Ribosomes?<br />

Since protein synthesis is an<br />

indispensable part of life, many antibiotics<br />

inhibit the activity of bacterial ribosomes,<br />

and sarecycline is no exception. As a<br />

complex—an assembly of multiple subunits<br />

that carry out a function together—the<br />

ribosome is made of ribosomal RNA<br />

(rRNA) associated with certain ribosomal<br />

proteins. Translation, the process it<br />

catalyzes, involves messenger RNAs<br />

(mRNAs) and transfer RNAs (tRNAs). The<br />

mRNA contains information ‘copied’ from<br />

the DNA that the ribosome must ‘read and<br />

translate.’ The tRNA contains nucleotides<br />

that recognize specific, three-base long<br />

mRNA sequences and the amino acid that<br />

corresponds to this sequence. The ribosome<br />

consists of large and small subunits, which<br />

are responsible for different steps of the<br />

process. The small subunit binds to the<br />

mRNA strand and identifies the correct<br />

tRNA molecule for every three bases within<br />

the decoding center. The large subunit then<br />

catalyzes the addition of the new amino<br />

acid to the growing polypeptide<br />

(protein) chain, which exits<br />

the ribosome through a<br />

structure called the nascent<br />

peptide exit tunnel (NPET).<br />

This process is how cells<br />

make proteins.<br />

Structural biologists have<br />

characterized the binding<br />

mechanisms of many antibiotics<br />

with ribosomes of model<br />

bacteria like E. coli and Thermus<br />

thermophilus. For first- and<br />

second-generation tetracyclines,<br />

all existent structures suggest that<br />

they bind to the decoding center<br />

of the small ribosomal subunit,<br />

inhibiting mRNA-tRNA interactions<br />

and slowing protein synthesis. The<br />

interaction patterns that Lomakin and<br />

colleagues characterized with cryo-EM<br />

agree with models of other tetracyclines.<br />

They show that the stacking of three<br />

hydrophobic layers stabilizes the binding of<br />

sarecycline in the decoding center of the C.<br />

acnes ribosome and inhibits tRNA arrival.<br />

Besides the canonical binding site,<br />

researchers were surprised to discover that<br />

sarecycline has a second binding site (SBS)<br />

on the C. acnes large ribosomal subunit,<br />

in the NPET. Here, sarecycline blocks<br />

the NPET and is thought to suppress the<br />

growth of the peptide chain. This binding<br />

site is specific to the C. acnes ribosome,<br />

as X-ray crystallography of sarecycline in<br />

complex with the Thermus thermophilus<br />

ribosome—also performed by the Bunick<br />

Lab—showed only the canonical binding<br />

site. Based on indirect experiments,<br />

researchers speculated that sarecycline<br />

could probably bind to both sites with<br />

similar affinities, and the sarecycline<br />

molecule in the SBS may assist with<br />

function in the canonical binding site.<br />

The paper compared this binding<br />

interaction with an antibiotic from<br />

another structural family, tetracenomycin<br />

X, which was recently shown to bind to<br />

the E. coli ribosome at a similar site. The<br />

team postulated that certain uridine bases<br />

were important in this interaction, and<br />

mutations from uridine to another base,<br />

cytosine, would confer resistance. However,<br />

Lomakin is not too worried about bacteria<br />

gaining sarecycline resistance, compared<br />

to other tetracyclines. “For sarecycline,<br />

we have an additional site on the large<br />

ribosomal subunit, encoded<br />

by a different gene than<br />

the small ribosomal<br />

subunit. The probability<br />

of simultaneously getting<br />

mutations on both of them<br />

is the multiplication<br />

of getting mutations<br />

on each, so it is very<br />

low,” Lomakin said.<br />

www.yalescientific.org<br />

May 2023 Yale Scientific Magazine 17


FOCUS<br />

Dermatology<br />

Potential Antimicrobial Properties<br />

Using cryo-EM, the researchers<br />

managed to capture the first highresolution<br />

structure of the C. acnes<br />

ribosome. They also examined the<br />

ribosomal proteins attached to the<br />

ribosomal RNA and explored how the C.<br />

acnes ribosome’s catalytic mechanisms<br />

could differ from other known bacterial<br />

models. This knowledge would help<br />

inform the future design of antibiotics<br />

against C. acnes.<br />

But of particular interest to the team<br />

were the bacterial small ribosomal subunit<br />

protein 22 (bS22) and the bacterial large<br />

ribosomal subunit protein 37 (bL37).<br />

These proteins are normally part of the<br />

ribosome and help synthesize proteins,<br />

but independent of the complex, they have<br />

displayed antimicrobial properties. C.<br />

acnes exists in normal skin, so researchers<br />

wonder if it helps defend the skin against<br />

other pathogenic bacteria. “From a<br />

dermatology perspective, we know C. acnes<br />

lives in our follicles and pilosebaceous units<br />

as a commensal organism—only certain<br />

strains of it are pathogenic for acne. We<br />

are trying to probe whether or not C. acnes<br />

has a natural defense mechanism against<br />

Staphylococcus aureus, which is a major<br />

pathogenic skin organism,” Bunick said.<br />

They discovered that the bS22 could inhibit<br />

the growth of E. coli and S. aureus while the<br />

bL37 only affected S. aureus but not E. coli.<br />

The next step down the antimicrobial<br />

properties path was to understand whether<br />

these proteins were present independent<br />

of the ribosome. Usually, ribosomal<br />

proteins form a complex with ribosomal<br />

RNAs to catalyze protein synthesis, but<br />

additional functions outside of ribosomes<br />

are possible. Bunick proposes that C. acnes<br />

may either secrete these peptides directly<br />

or release them when they die and lose<br />

their membranes.<br />

Sarecycline: The Better Acne-Biotic?<br />

Sarecycline was introduced in 2018 as a<br />

drug with higher specificity and fewer side<br />

effects than minocycline and doxycycline.<br />

However, primarily due to pricing issues,<br />

it only has about six percent of the<br />

prescription market for oral tetracycline<br />

in dermatology. To Bunick, sarecycline<br />

deserves more recognition. “At least to my<br />

knowledge, it is the only FDA-approved<br />

PHOTOGRAPHY BY EMILY POAG<br />

Dr. Christopher Bunick (left) and Dr. Ivan Lomakin (right) discussing a model of the ribosome.<br />

drug that targets two active centers of the<br />

ribosomes currently,” he said.<br />

The human gastrointestinal tract<br />

contains many beneficial Gram-negative<br />

bacteria. Since sarecycline is more specific<br />

to certain Gram-positive bacteria and<br />

spares Gram-negative bacteria, it causes<br />

fewer side effects in the gastrointestinal tract<br />

while effectively targeting Gram-positive<br />

C. acnes. Doxycycline is photosensitive,<br />

so certain users may experience rashes,<br />

itching, or severe sunburn, while<br />

sarecycline is not. Sarecycline is also<br />

less hydrophobic, meaning a decreased<br />

possibility of diffusing through the bloodbrain<br />

barrier and causing dizziness, vertigo,<br />

or tubular disturbance.<br />

The Bunick lab partners with Almirall, the<br />

pharmaceutical company that licenses and<br />

ABOUT THE AUTHOR<br />

sells sarecycline in the United States. “Our<br />

laboratory [work] has been predominantly<br />

keratins, intermediate filaments, and the<br />

skin barrier for over a decade. But [learning<br />

about sarecycline] presented a unique<br />

opportunity as an entryway into a new area<br />

of research understanding the molecular<br />

mechanisms of dermatology drugs.<br />

Sometimes the science leads you to where<br />

you need to be,” Bunick said. He does<br />

not rule out the possibility of developing<br />

a fourth-generation tetracycline. This<br />

paper was the first to publish a C. acnes<br />

ribosomal structure. Given the new<br />

information about multiple active sites, it is<br />

possible to further optimize the structure<br />

of the antibiotic to achieve more precise<br />

treatment of the infection behind your<br />

bumps and whiteheads. ■<br />

CRYSTAL LIU<br />

CRYSTAL LIU is a sophomore at Pierson College majoring in molecular, cellular and developmental<br />

biology. Besides writing for <strong>YSM</strong>, she is involved in the Irish Lab, Chinese Undergraduate Students<br />

at Yale, and Club Jump Rope. You can also find her trying out new restaurants and boba, playing<br />

IM volleyball, and listening to a lot of Mandopop and Cantopop songs.<br />

THE AUTHOR WOULD LIKE TO THANK Christopher Bunick and Ivan Lomakin for for their time<br />

and enthusiasm about their research.<br />

FURTHER READING:<br />

Lomakin, I. B., Devarkar, S. C., Patel, S., Grada, A., & Bunick, C. G. (2023). Sarecycline inhibits<br />

protein translation in Cutibacterium acnes 70S ribosome using a two-site mechanism. Nucleic<br />

Acids Research. https://doi.org/10.1093/nar/gkad103<br />

Batool, Z., Lomakin, I. B., Polikanov, Y. S., & Bunick, C. G. (2020). Sarecycline interferes with tRNA<br />

accommodation and tethers mRNA to the 70s ribosome. Proceedings of the National Academy of<br />

Sciences, 117(34), 20530–20537. https://doi.org/10.1073/pnas.2008671117<br />

Grada, A., Del Rosso, J. Q., Moore, A. Y., Stein Gold, L., Harper, J., Damiani, G., Shaw, K., Obagi, S.,<br />

Salem, R. J., Tanaka, S. K., & Bunick, C. G. (2022). Reduced blood-brain barrier penetration of acne<br />

vulgaris antibiotic sarecycline compared to minocycline corresponds with lower lipophilicity.<br />

Frontiers in Medicine, 9. https://doi.org/10.3389/fmed.2022.1033980<br />

18 Yale Scientific Magazine May 2023 www.yalescientific.org


Ecology<br />

FOCUS<br />

ANIMALS<br />

AGAINST<br />

RISING<br />

TIDES<br />

BY ABIGAIL JOLTEUS<br />

ART BY LUNA AGUILAR<br />

How mussels flex to keep<br />

coastal ecosystems afloat<br />

Due to climate change, sea levels could rise twelve inches<br />

in the next three decades, equivalent to the measured<br />

rise seen over the last century. This rise stresses<br />

vegetated coastal ecosystems, which include mangroves, salt<br />

marshes, and seagrasses. Coastal ecosystems provide habitats<br />

for a wide variety of wildlife and protect both humans and<br />

animals from storms. They also stabilize the shoreline, filter<br />

nutrients, and store carbon dioxide from the atmosphere in<br />

the ground. “Coastal ecosystems are very near and dear to my<br />

heart,” said Sinéad Crotty, associate director of science at the<br />

Yale Carbon Containment Lab, said.<br />

In a recent paper published in Nature Communications,<br />

Crotty examined the direct and indirect effects of one<br />

unassuming invertebrae—mussels—on the persistence of<br />

vegetated coastal ecosystems.<br />

Even small changes in sea levels can substantially alter these<br />

ecosystems through coastal flooding, resulting in higher<br />

storm surges—the rise of seawater during a storm—and an<br />

influx of saltwater into freshwater habitats. Rising sea levels<br />

www.yalescientific.org<br />

have prompted the increase in resources directed to vertical<br />

and horizontal accretion, a natural process that results in a<br />

change in the elevation of salt marshes. Accretion can indicate<br />

how well a salt marsh is persisting in spite of changes in sea<br />

level, and, according to Crotty, refers to how the marsh moves<br />

upwards to compensate for sea level rise. It can increase<br />

vertically or horizontally, in the landward direction of the<br />

boundary of the marsh.<br />

Studying accretion is particularly important because it helps<br />

prevent a phenomenon known as drowning, in which the<br />

vegetated area of a salt marsh is converted into an open water<br />

area. This originally looks like a small pond that eventually<br />

grows larger. As the salt marshes drown, the vital services<br />

that they provide, including habitation, storm buffering, and<br />

carbon storage, also disappear, destabilizing the wildlife around<br />

it.“We care deeply about accretion because for marshes to not<br />

drown, we need the rate of accretion to be greater than the rate<br />

of sea level rise,” said Hallie Fischman, a Ph.D. student at the<br />

University of Florida and an author of the paper.<br />

May 2023 Yale Scientific Magazine 19


FOCUS<br />

Ecology<br />

Historically, studies on accretion<br />

focused on environmental factors, such<br />

as tidal range and sediment supply. The<br />

tidal range consists of the difference<br />

between the highest and lowest point<br />

of the tide, and sediment supply refers<br />

to the availability and transport of<br />

sediment. However, organisms can also<br />

shape their environment, which includes<br />

modifying accretion processes. This<br />

concept is known as faunal engineering.<br />

It refers to animals that provide habitats,<br />

nutrients, or some other alterations that<br />

allow other organisms, as Crotty put it,<br />

to ‘persist and thrive.’<br />

Mussels: The Underdogs Of Coastal<br />

Ecosystems<br />

One of the most abundant faunal<br />

engineers present in salt marshes in<br />

the United States are Atlantic ribbed<br />

mussels. Mussels can be easy to miss in<br />

these vast ecosystems. Yet even though<br />

these organisms are tiny, their functions<br />

are vital—they can, either directly or<br />

indirectly, alter plant growth and improve<br />

water quality by removing organic<br />

matter and unwanted particles. These<br />

particles and organic matter are filtered<br />

by mussels, processed, and subsequently<br />

excreted. Therefore, mussels help with<br />

sediment deposition, the excretion of<br />

Atlantic ribbed mussels.<br />

It was a crazy idea that we could feed mussels<br />

orange chalk, they would poop it out, and<br />

we could follow it across the marsh.<br />

digested organic material. Mussels are<br />

also an important food source for many<br />

terrestrial and aquatic organisms.<br />

Researchers at the Yale Carbon<br />

Containment Lab and the University of<br />

Florida were interested in quantifying<br />

the effects of the Atlantic ribbed mussel<br />

on accretion in southeastern US salt<br />

marshes. They performed three field<br />

experiments to fulfill this objective.<br />

The first field experiment was to<br />

investigate whether the sediments<br />

deposited by mussels could supply<br />

marshes beyond the areas where the<br />

mussels were gathered. Where exactly<br />

was the sediment spreading? To answer<br />

this question, the researchers tagged<br />

biodeposits that were already on the<br />

mound. Then, the fluorescent chalk<br />

was mixed with already deposited<br />

biodeposits, and the researchers came<br />

PHOTOGRAPH COURTESY OF FLICKR<br />

back to trace the movement at night.<br />

“It was a crazy idea that we could feed<br />

mussels orange chalk, they would poop<br />

it out, and we could follow it across the<br />

marsh,” Fischman said.<br />

The researchers returned at night and<br />

used black light detection to trace the<br />

distribution of the fluorescently-tagged<br />

biodeposits. Blacklight, or ultraviolet<br />

(UV) light, is a tool commonly used to<br />

detect fluorescently-tagged materials.<br />

The maximum distance that fluorescent<br />

biodeposits traveled was measured in<br />

every direction.<br />

Interestingly, the team discovered<br />

that the biodeposits were quickly<br />

redistributed beyond the areas where<br />

mussels were present. To confirm<br />

these results, the researchers collected<br />

approximately ten mussels from each<br />

of their six mounds, brought them to<br />

the University of Georgia’s laboratory,<br />

and fed them a mixture of seawater and<br />

chalk, which resulted in the excretion of<br />

fluorescently-tagged biodeposits. After<br />

the previous fluorescent material was<br />

washed away, the researchers planted the<br />

mussels in the respective mounds and<br />

performed the study again, subsequently<br />

confirming their previous findings.<br />

One limitation of this experiment that<br />

the researchers hope will be addressed<br />

in future studies is that the dye in the<br />

biodeposits fluoresced for only the first<br />

twenty-four hours, so the study was<br />

performed on a limited time scale.<br />

In the second field experiment, the<br />

researchers wanted to investigate the effects<br />

of cordgrass, also known as marsh grass,<br />

and mussels on sediment deposition at<br />

different marsh elevations. Seven different<br />

scenarios were tested in two zones in the<br />

state of Georgia for a month: the creekhead,<br />

where a narrow inlet called a tidal creek<br />

20 Yale Scientific Magazine May 2023 www.yalescientific.org


Ecology<br />

FOCUS<br />

to sediment deposition and vertical<br />

accretion in salt marshes.<br />

New Ideas For Mitigating Sea Level Rise<br />

A salt marsh in Georgia.<br />

enters onto the marsh, and the marsh<br />

platform, the main flat surface of the mark<br />

that extends landward.<br />

Cordgrass was found to have no<br />

significant effect on sediment deposition<br />

in both zones, which further highlights<br />

the importance of mussels. As for mussels,<br />

after performing statistical analysis,<br />

the researchers discovered a positive<br />

correlation between the number of mussels<br />

and increased sediment deposition. The<br />

implications of this study are limited by the<br />

size of the areas that were observed.<br />

In the third field experiment, to assess<br />

the potential effects of mussels on marsh<br />

accretion at the level of a creekshed, a<br />

smaller version of a watershed, researchers<br />

manipulated the presence and population<br />

size of mussels. Approximately two hundred<br />

thousand mussels were manually moved<br />

from one creekhead to another. A control<br />

creekhead side in the same marsh was also<br />

established. With the help of a tool called<br />

the Digital Elevation Model (DEM), the<br />

researchers were able to assess the elevation<br />

of the creekheads after three years. DEM<br />

was created using drone imagery, which<br />

was then filtered and edited to remove<br />

vegetation to focus on the sediment. The<br />

team discovered that the creek from which<br />

the mussels were removed decreased in<br />

elevation, but the creek to which mussels<br />

were added increased in elevation. Mussels<br />

were putting in the work.<br />

To further explore and validate the<br />

conclusions from their field experiments,<br />

the researchers used the Delft-3D-<br />

BIVALVES model, a digital tool to<br />

IMAGE COURTESY OF FLICKR<br />

create simulations, generating different<br />

scenarios that mimicked salt marshes in<br />

the region. This model determined that<br />

the highest sediment accretion was found<br />

on mussel aggregations using simulations<br />

based on the assumption that mussels<br />

filter the water column—which refers to<br />

the space between the surface and floor of<br />

a body of water. Mussels expel the filtered<br />

content and their feces on mounds, which<br />

facilitates a build-up of sediments that<br />

increases the elevation of the salt marsh.<br />

“While the manual labor and<br />

methodology development were at times<br />

challenging, I think ultimately this has<br />

been one of the most collaborative and<br />

gratifying scientific efforts that I have<br />

been a part of,” Crotty said. Each of<br />

these field experiments in addition to<br />

the simulation models contributed to<br />

the overall claim that mussels increase<br />

salt marsh accretion. The results suggest<br />

that mussels contribute significantly<br />

ABOUT THE AUTHOR<br />

“The coolest takeaway of this study<br />

is that mussels increase salt marsh<br />

accretion, which means that mussels<br />

are important in helping marshes keep<br />

up with sea level rise,” Fischman said.<br />

Other researchers can use the insights<br />

provided by this study to direct their<br />

research projects on animals similar to<br />

mussels. Mussels may not, however, be<br />

the only animals that are contributing to<br />

the health of their ecosystems.<br />

Due to climate change, small animals<br />

are adapting their roles to their<br />

changing environment. Understanding<br />

the behavior of these animals can help<br />

guide future research on other types<br />

of terrestrial and marine ecosystems.<br />

“Relatively small animals are increasing<br />

in their relative importance and the roles<br />

that they play in response to the changes<br />

that climate change is implementing,”<br />

Crotty said.<br />

As for next steps, Fischman is interested<br />

in the effect of mussels on nitrogen<br />

cycling, which is a cycle of various<br />

processes in which nitrogen moves<br />

through living and non-living things in<br />

the environment.<br />

As climate change continues to worsen,<br />

an additional rise in sea levels is inevitable.<br />

Among its dangers are more frequent and<br />

intense floods, higher storm surges, and loss<br />

and alteration of coastal habitats. Future<br />

studies, including those on overlooked<br />

parts of an ecosystem, can hopefully help<br />

mitigate its harmful effects. ■<br />

ABIGAIL JOLTEUS<br />

ABIGAIL JOLTEUS is a sophomore in Berkeley College studying Ecology and Evolutionary Biology.<br />

In addition to managing the website for <strong>YSM</strong>, she conducts research in the Konnikova Lab.<br />

THE AUTHOR WOULD LIKE TO THANK Sinéad Crotty and Hallie Fischman for their time and<br />

enthusiasm about their research.<br />

FURTHER READING:<br />

Jones, Clive G., et al. “Organisms as Ecosystem Engineers.” Ecosystem Management, 1994, pp. 130–<br />

47, https://doi.org/10.1007/978-1-4612-4018-1_14.<br />

FitzGerald, D. M. & Hughes, Z. Marsh Processes and Their Response to Climate Change and Sea-<br />

Level Rise. Annu. Rev. Earth Planet. Sci. 47, 481–517 (2019).<br />

www.yalescientific.org<br />

May 2023 Yale Scientific Magazine 21


FOCUS<br />

Public Health<br />

FATAL ATTRACTION<br />

Using fly pheromones against disease<br />

A natural tsetse fly odorant could<br />

help prevent African sleeping sickness<br />

BY CINDY MEI<br />

ART BY COURT JOHNSON<br />

From evoking long-forgotten memories through nostalgic scents to detecting<br />

imminent danger through noxious odors, smells hold undeniable power.<br />

Our sense of smell has served as a prime mechanism for survival since the<br />

beginning of time. Much of the work in the lab of John Carlson, a Yale professor<br />

of Molecular, Cellular, and Developmental Biology, is dedicated to studying the<br />

intricate mechanisms of Drosophila (fruit fly) olfaction: how do these insects detect<br />

and behave in the presence of volatile pheromones? An example of chemosensation,<br />

these pungent odorants—chemical compounds that have a smell—produced by<br />

organisms facilitate sexual attraction and mating by affecting behavior. The lab is<br />

interested in studying chemosensation as a method to control populations of insects<br />

that spread disease—such as the tsetse flies, insects that are responsible for spreading<br />

African trypanosomes, the causative agents of African sleeping sickness in Sub-<br />

Saharan regions.<br />

22 Yale Scientific Magazine May 2023 www.yalescientific.org


Public Health<br />

FOCUS<br />

In a paper published in Science earlier<br />

this year, a team of researchers conducted<br />

a study to find natural odorants that<br />

may control the behavior of tsetse flies.<br />

Led by Shimaa Ebrahim, a postdoctoral<br />

researcher in the Carlson lab, the project<br />

was conducted in collaboration with Hany<br />

Dweck, an associate scientist in the Carlson<br />

lab, and Brian Weiss, a senior research<br />

scientist at the Yale School of Public Health.<br />

“I fell in love with the [tsetse fly],” Ebrahim,<br />

who studies the courtship behavior of<br />

Drosophila, said. Weiss echoed Ebrahim’s<br />

fascination, pointing out behaviors unique<br />

to the tsetse flies, such as the live birth and<br />

nurturing of their young, in contrast to the<br />

majority of insects, which lay eggs.<br />

Importantly, tsetse flies feed exclusively<br />

on vertebrate blood, leading to the<br />

transmission of Trypanosoma brucei<br />

(trypanosomes), a classification of<br />

protozoan parasites that cause African<br />

sleeping sickness and nagana in humans<br />

and domesticated animals, respectively.<br />

These diseases have devastating effects:<br />

nagana is responsible for an average loss of<br />

4.5 billion dollars in resources every year<br />

in Africa. If left untreated, African sleeping<br />

sickness has a one hundred percent<br />

mortality rate. Unfortunately, access to<br />

treatment is not available everywhere.<br />

“Most of the drugs used to treat sleeping<br />

sickness are arsenic-based and horribly<br />

toxic. Very recently, there’s been some<br />

newly-developed medications, and they're<br />

much less toxic—but they’re much more<br />

expensive,” said Weiss, who studies tsetse<br />

flies and their associated microorganisms.<br />

To find alternative solutions, the<br />

researchers turned their attention to<br />

preventative measures. According to Weiss,<br />

the best solution to reduce fly populations is<br />

to use traps, as they are cheap and effective.<br />

However, not much is understood about<br />

the chemical signaling of tsetse flies, which<br />

may be key to luring the flies to traps. “If<br />

you want to control any insect that could<br />

cause disease or damage to any crop, you<br />

have to study their behavior to find the way<br />

to control this insect,” Ebrahim said.<br />

The Role Of Smell In Mating<br />

The researchers utilized the tsetse fly<br />

species Glossina morsitans. While Glossina<br />

fuscipes is the most abundant species in<br />

Kenya, they are difficult to rear in the<br />

insectary, according to Weiss. To examine<br />

possible odorants in sexual attraction, the<br />

researchers first studied tsetse fly mating<br />

behaviors. When paired together, G.<br />

morsitans males initiate mating with G.<br />

morsitans virgin females within seconds,<br />

and copulation continues on average for<br />

an hour. However, this reaction was not<br />

observed when G. morsitans males were<br />

paired with mated females, suggesting<br />

that there may be a difference in chemical<br />

signaling that results in the male’s<br />

behavioral responses.<br />

To determine whether differences<br />

in mating are driven by olfaction,<br />

pheromone extracts were obtained from<br />

the exoskeleton, also called the cuticle<br />

(the layer that covers the extracellular<br />

surface of the fly), of male and female<br />

flies that were soaked and gently shaken<br />

in hexane for ten minutes. Dummy tsetse<br />

flies made out of yarn were sprayed with<br />

these extracts and placed in a container<br />

with male G. morsitans, and a measure<br />

of attraction was determined by the<br />

percentage of males that initiated mating<br />

and stayed attached to the decoy flies for<br />

more than five minutes. However, the<br />

males were not attracted at all, suggesting<br />

that any odorants associated with mating<br />

are stored beyond the cuticles.<br />

After soaking another set of tsetse flies<br />

in hexane for twenty-four hours, it was<br />

observed that males were attracted sixty<br />

percent of the time to dummies sprayed<br />

with extracts from virgin females and<br />

twenty-seven percent of the time with<br />

extracts from mated females, with no<br />

response observed with male extracts.<br />

This observation indicates that there may<br />

be a difference in the composition of the<br />

extracts that made male flies more attracted<br />

to virgin than mated female G. morsitans.<br />

The longer soaking time may also explain<br />

why these compounds were not detected as<br />

potential pheromones in earlier research.<br />

The Discovery Of A Key Pheromone<br />

To determine if differences in compound<br />

composition were responsible for mating<br />

behaviors, the researchers obtained the<br />

chemical profile of the extractions via gas<br />

chromatography-mass spectrometry (GC-<br />

MS), which separates and detects different<br />

compounds. GC-MS identified three fatty<br />

acids and three fatty acid methyl esters that<br />

were not present in the ten-minute hexane<br />

immersion, which suggests the pheromones<br />

stored in internal glands may play a part in<br />

facilitating attraction.<br />

To test this hypothesis, the researchers<br />

repeated the previous experiment by<br />

spraying the dummy flies with each of<br />

these six compounds. They found that the<br />

male flies were strongly attracted to certain<br />

compounds that are present in higher<br />

levels in virgin females, such as methyl<br />

palmitoleate (MPO)—which attracted G.<br />

morsitans males eighty-seven percent of<br />

the time even when diluted—methyl oleate<br />

(MO), and methyl palmitate (MP). The<br />

www.yalescientific.org<br />

May 2023 Yale Scientific Magazine 23


FOCUS<br />

Public Health<br />

male fly stayed attached to the dummy for<br />

a prolonged period of time, suggesting that<br />

these compounds also act as arrestants—<br />

halting all motion—to prevent premature<br />

interruption of mating. Clearly, smell<br />

seemed to play a powerful role in mating!<br />

Next, the researchers sought to investigate<br />

cellular mechanisms that may facilitate<br />

the observed behavioral responses.<br />

Removing G. morsitans males’ antennae<br />

eliminated their attraction response,<br />

suggesting that the observed behavioral<br />

responses in mating are facilitated by scent.<br />

Furthermore, research has suggested that<br />

volatile odors are detected via the trichoid<br />

sensilla, a sensory organ located in the<br />

antenna of the fly.<br />

In a method called single-sensillum<br />

electrophysiology, the researchers<br />

obtained recordings of trichoid sensilla<br />

response to odors detected in the air<br />

by antenna. Initially, only MPO elicited<br />

excitatory responses from both sexes, but<br />

particularly from males. After reducing<br />

the distance from which the odor was<br />

delivered, activation in neurons was seen<br />

with MP, MO, and MPO, correlating<br />

with the behavioral results observed<br />

in earlier experiments. However, there<br />

was little to no response in olfactory<br />

neurons to these six compounds in G.<br />

fuscipes, another tsetse species that is<br />

the prominent vector of trypanosomes<br />

in east Africa. This finding suggested<br />

that these pheromones are specific to G.<br />

morsitans mating mechanisms. Indeed,<br />

it was found that G. morsitans males<br />

made no attempt to mate with untreated<br />

G. fuscipes females; however, when G.<br />

fuscipes females were sprayed with MPO,<br />

the males began to engage, suggesting<br />

that MPO may act as an<br />

aphrodisiac, a stimulant<br />

for sexual desire, for G.<br />

morsitans males.<br />

Could Infection Change<br />

Mating?<br />

The last study<br />

examined if these<br />

findings held for<br />

tsetse flies infected<br />

with trypanosomes,<br />

which is the<br />

ultimate target for<br />

traps to prevent<br />

the spread of African sleeping sickness.<br />

There were no changes in single-sensillum<br />

electrophysiology, meaning there was no<br />

change in neuronal response. However,<br />

there were significant behavioral changes<br />

observed in mating.<br />

When paired together, uninfected<br />

virgin female G. morsitans mated with<br />

infected and uninfected males at the same<br />

frequency. However, uninfected virgin<br />

male G. morsitans mated with uninfected<br />

females one hundred percent of the<br />

time over infected females, suggesting<br />

that there may be a compound that<br />

lowers the sexual receptivity of infected<br />

females and acts as a repellent against<br />

G. morsitans males. The group hopes to<br />

further study twenty-one compounds<br />

that were identified in GC-MS as specific<br />

to infected flies. “I'm interested to study<br />

if this compound is produced as a defense<br />

against the parasites,” Ebrahim said.“We<br />

don't know if those compounds were<br />

produced by the tsetse fly in response<br />

to an infection, or maybe they were<br />

produced by the parasites themselves,”<br />

Weiss said.<br />

Harnessing The Power Of Pheromones<br />

The results of the study suggest that<br />

MPO acts specifically as an attractant,<br />

aphrodisiac, and arrestant on G. morsitans<br />

males to activate circuits that mediate<br />

olfactory attraction, sexual desire, and the<br />

halting of movement, respectively. The<br />

usage of MPO in traps holds great promise<br />

from both an environmental and economic<br />

perspective. “Compounds from the fly itself<br />

[…] will be less toxic if we want to use it in<br />

the field compared to other compounds like<br />

DEET,” Ebrahim explained. These natural<br />

ABOUT THE AUTHOR<br />

compounds are also much less expensive<br />

than DEET, which makes implementation<br />

of tsetse fly control more realistic in<br />

developing countries.<br />

In the future, the researchers hope to test<br />

MPO in Kenya with collaborators, who are<br />

currently using tsetse fly host odors such<br />

as cow urine as attractants. “If we combine<br />

MPO with natural host odors, it might<br />

increase the efficiency of control for a trap,”<br />

Ebrahim said. “A more specific odor might<br />

attract more flies and reduce the number<br />

of cases of infection by trypanosomes.”<br />

However, there are challenges<br />

validating field work with lab work, since<br />

the flies in the experiment are different<br />

from those found in a typical African<br />

savanna. In addition, in the real world,<br />

there are many fluctuating and uncertain<br />

factors, according to Ebrahim. Despite<br />

these challenges, the group remains<br />

undeterred, and their passion stays<br />

vibrant. “You will have to be optimistic<br />

and creative for the biggest experiments<br />

you design,” Ebrahim said. ■<br />

CINDY MEI<br />

CINDY MEI is a sophomore in Grace Hopper studying neuroscience. In addition to writing for <strong>YSM</strong>,<br />

she serves as communications chair on Yale Math Competitions and volunteers with Yale DEMOS<br />

and Yale New Haven Hospital. She also conducts epilepsy and Tourette’s syndrome research at the<br />

Yale School of Medicine.<br />

THE AUTHOR WOULD LIKE TO THANK Shimaa Ebrahim, Brian Weiss, and John Carlson for their<br />

time and enthusiasm in answering questions and providing interactive insight about their research.<br />

FURTHER READING:<br />

Ebrahim, S.A.M., Dweck, H.K.M., Weiss, B.L., & Carlson, J.R. (2023). A volatile sex attractant of tsetse<br />

flies. Science, 379 (6633), doi: 10.1126/science.ade1877<br />

24 Yale Scientific Magazine May 2023 www.yalescientific.org


Environmental Engineering<br />

FEATURE<br />

SEEDING<br />

ROBOTS<br />

WOODEN CORKSCREW<br />

ROBOTS PLANT SEEDS<br />

BY MADELEINE POPOFSKY<br />

Look, up in the sky! It’s a bird! It’s a plane! It’s… hundreds of<br />

autonomous self-burying seed carriers? These small wooden<br />

contraptions are built with a unique design that lets them bury<br />

a seed into the ground after dropping from a great height. While<br />

unlikely to drop into your backyard, this new invention spearheaded<br />

by Lining Yao of Carnegie Mellon University and Teng Zhang of<br />

Syracuse University could change the face of reforestation via air. The<br />

design for these carriers is inspired by Erodium seeds and their natural<br />

dispersal mechanisms, and they are made using natural materials such<br />

as wood. The carriers provide a nature-based solution to our manmade<br />

problems regarding habitat loss, forest shrinkage, and even<br />

agricultural complications.<br />

Aerial seeding—scattering seeds by plane, drone, or helicopter—<br />

is an invaluable technique when it comes to wildland restoration,<br />

reforestation, and agriculture, especially for large swaths of hard-toaccess<br />

land. However, the scattered seeds often fail to penetrate the<br />

ground. This dramatically decreases their chances of germination, as<br />

they can get eaten by wildlife or swept away by harsh weather conditions.<br />

The device is closely modeled on the seeds of Erodium, a flowering<br />

plant that has seeds with a special design: a coiled body and single<br />

twisting tail that allows them to bury into the soil. “It’s very hard to<br />

reproduce the performance and also the biodegradable nature of the<br />

Erodium seeds,” Zhang said.<br />

After many rounds of testing, the final design has a twist: three<br />

tails instead of one. “These three points provide a stable contact<br />

between the structure and<br />

the soil,” Zhang said.<br />

Imagine a propeller<br />

with three blades<br />

circling each other<br />

on top—these are the<br />

three tails. In the center,<br />

where the three tails meet,<br />

a coil extends downward<br />

in a straight line—this is the coil<br />

body. At the end of the coil body lies the seed<br />

tip, where the seed is stored. In addition to the<br />

three tails, the other main innovation is the coil,<br />

which provides the mechanical force to allow the<br />

carriers to drill into the ground. The researchers<br />

treated the wood used to make the coil body<br />

with multiple rounds of chemical<br />

treatment and mechanical<br />

deformation in order to<br />

create its twisting shape.<br />

ART BY KARA TAO<br />

www.yalescientific.org<br />

The carrier is rain-driven—another concept borrowed from<br />

Erodium seeds, which change shape depending on humidity. The<br />

wood cells in the coil swell during rainfall, with those on the inside<br />

swelling more than those on the outside, causing the coil to unwind<br />

and the seed to be drilled into the ground. As the coil dries, the<br />

cells on the inside shrink more than<br />

those on the outside, promoting<br />

another coiling mechanism in<br />

the opposite direction that<br />

further embeds the seed.<br />

The main challenges<br />

faced by the researchers<br />

included field tests that<br />

could be done best only in<br />

the spring, resulting in months of<br />

wait time until conditions were suitable,<br />

in addition to day-of weather concerns.<br />

Furthermore, the researchers created a simulation<br />

to test the device’s performance which proved difficult,<br />

considering friction and the many connections between<br />

the tails and coil body.<br />

The carriers have a few issues: they can be negatively<br />

affected by extreme weather conditions, the tip-coil connection<br />

can sometimes break, and the tails can tangle during release. The<br />

team aims to fix these issues as well as test other types of materials.<br />

The tested carriers were made of white oak, but other woods or<br />

materials could potentially be used with the design. A larger material<br />

library will enhance the feasibility of production in different regions.<br />

Additionally, the researchers are exploring other dimensions for the<br />

seed carriers that could improve their performance.<br />

Currently, the carriers are lovingly crafted by hand—which is<br />

not a production method that can continue long-term. The team<br />

is now focusing on producing on an industrial scale. “The cost [of<br />

production] is really about the time and the effort. The material<br />

cost is relatively cheap,” Zhang said.<br />

Yao, Zhang, and their team are currently seeking partners and<br />

stakeholders to expand their impact. “Responsive and functional<br />

structures that are powered by renewable energy could play a<br />

critical role in natural contexts, for ecological purposes such as<br />

restorations and environmental monitoring,” Yao said.<br />

When faced with a problem, sometimes the best inspiration is to<br />

look to nature. That has certainly proved to be the case with these<br />

self-drilling seed carriers. And in ten years’ time, maybe the future<br />

of our world’s forests will be saved by a swarm of plucky, threetailed<br />

robots falling from the sky. ■<br />

May 2023<br />

Yale Scientific Magazine<br />

25


FEATURE<br />

Anatomy<br />

YOUR UNIQUE FINGERPRINT<br />

GENETIC AND NON-GENETIC DETERMINANTS OF<br />

FINGERPRINT PATTERN FORMATION<br />

BY ELISA HOWARD<br />

ART BY BREANNA BROWNSON<br />

Look at your hands. Look closely at the patterns drawn on<br />

the tips of your fingers. The fingerprint is present from<br />

birth, unchanging over the human lifespan, and unique<br />

to each and every individual. Even identical twins with the<br />

same genes exhibit distinct fingerprints. So, how does your<br />

fingerprint develop? And what factors contribute to the unique<br />

patterns that you see?<br />

Fingerprints exhibit three main pattern types: arches, loops,<br />

and whorls. Fingerprint ridges begin to form in the twelfth<br />

week of gestation, the period between conception and birth,<br />

and the organization of the fingerprint pattern is defined by<br />

week fourteen. However, little is known about the biological<br />

mechanisms underlying fingerprint variation. In a recent paper<br />

published in Cell, researchers at the University of Edinburgh<br />

and the Shanghai Institute of Nutrition and Health provide<br />

insight into the genetic foundations of fingerprint development.<br />

“We are interested in individual molecules and genes and how<br />

they work together to create structure and form,” said Denis<br />

Headon, a senior research fellow at the University of Edinburgh<br />

and an author of the study.<br />

Leading the project, Shanghai Institute researchers in the<br />

Laboratory of Dermatogenomics performed genome-wide<br />

association studies (GWAS) linking fingerprint pattern type<br />

with genetics. A GWAS is a research approach that correlates<br />

variation in observable traits with variation in the DNA. The<br />

Shanghai researchers conducted GWAS of several thousand Han<br />

Chinese individuals characterized for the three main fingerprint<br />

patterns. This GWAS method identified forty-three locations of<br />

genes associated with developing arches, loops, or whorls.<br />

The researchers then studied the functions of fingerprintassociated<br />

genes and the timing of their activity in development.<br />

“Interestingly, locations in the genome that correlate with<br />

fingerprint type are populated by genes involved in limb<br />

formation, rarely skin development,” Headon said. That is, genes<br />

involved in embryonic limb formation appear as the predominant<br />

factors determining heritable variation in fingerprint patterns.<br />

The researchers also found that many of the fingerprint-associated<br />

genes identified through GWAS are not even active in the skin<br />

when the fingerprint forms. Rather, the genes function early in<br />

development to set up the proportions and shapes of the fingertips.<br />

As development progresses, the genes switch off. These findings can<br />

be understood in the context of correlative work from the twentieth<br />

century, which argues that the shape of the finger strongly influences<br />

fingerprint<br />

patterns. Thus,<br />

it appears<br />

that limb<br />

development<br />

genes dictate the<br />

presence or absence<br />

of arches, loops, or<br />

whorls through their involvement in<br />

finger shape.<br />

However, the GWAS results<br />

only explain part of the variation<br />

in fingerprints across the human<br />

population because fingerprint type<br />

is not entirely heritable. For instance,<br />

identical twins have different fingerprints,<br />

and the fingerprints of the left and right hand are<br />

not mirror images. “The same genome running through the process<br />

of making a fingerprint at different times, for different fingers,<br />

for different individuals will come up with a slightly different<br />

outcome,” Headon said. Therefore, rather than simply focusing<br />

on genes, it is important to consider development as a process.<br />

“The genes inform, but then there is a process of development that<br />

interprets and gives an outcome in the anatomy,” Headon said.<br />

How can this study help explain the distinct fingerprints of<br />

identical twins? If one identical twin has all arches, then the<br />

other twin is more likely to have all arches than a random,<br />

unrelated member of the population. In other words, there is<br />

at least some genetic influence. “But genetic variation will go<br />

through a developmental process that has a certain amount<br />

of randomness to it,” Headon said. Simply knowing the list<br />

of genes active in a particular tissue provides an incomplete<br />

understanding of how that tissue develops. “You need to<br />

abstract a step from that and say, ‘what is the process through<br />

which these genes operate together to produce a particular<br />

outcome?’” Headon said.<br />

Look at your hands again. How might your fingerprints<br />

have formed? ■<br />

26<br />

Yale Scientific Magazine<br />

May 2023<br />

www.yalescientific.org


FEATURE<br />

Materials Engineering<br />

Astrophysics<br />

FEATURE<br />

THE<br />

IMPOSSIBLE<br />

ART BY YUROU LIU<br />

STAR<br />

A NEWBORN STAR LIVING ON<br />

THE CUSP OF A BLACK HOLE<br />

BY ELIZABETH WATSON<br />

Most of the stars we see in the night sky are billions of<br />

years old, their light only just now reaching us from<br />

light-years away. But what lies beyond what we can see?<br />

The reach of the universe extends far beyond the stars that we’re<br />

able to observe with the naked eye.<br />

A team led by Florian Peißker, a postdoctoral researcher at the<br />

University of Cologne’s Institute of Astrophysics in Germany,<br />

recently discovered a newborn star named X3 whose existence<br />

defies all odds. Dubbed “the impossible star,” X3 is located over<br />

twenty-five thousand light-years away and is currently undergoing<br />

early stages of stellar formation in the vicinity of Sagittarius A*, the<br />

supermassive black hole at the heart of our galaxy. Star formation<br />

so close to a black hole was thought to be theoretically impossible,<br />

but X3 persists all the same.<br />

“I enjoy thinking about the opportunity to witness processes<br />

nobody else has seen before,” Peißker said. The paper, published in<br />

The Astrophysical Journal, is the product of two and a half years of<br />

work and explores how X3 was able to form in spite of Sagittarius A*.<br />

Star formation typically requires two conditions: relatively low<br />

temperatures and high gas density, neither of which holds true for<br />

the environments created by black holes. The area that Sagittarius A*<br />

occupies, known as the Galactic Center, is extremely hot and volatile.<br />

“This source should not exist in the first place because of the<br />

harsh environment of the supermassive black hole Sagittarius<br />

A*,” Peißker said. “The fact that we observe such a young object<br />

so close to Sgr A* implies that this is not the only [such object].<br />

It furthermore shows that star formation can occur, although the<br />

classical criteria are not fulfilled.”<br />

Previous research in the field identified clumps of silicon<br />

monoxide (SiO) gas near Sagittarius A* that may have been dense<br />

enough to permit high-mass star formation. A study in 2014<br />

suggested that these clumps originated from the Circumnuclear<br />

Disk (CND), a ring of molecular gas that surrounds Sagittarius A*.<br />

It was proposed that some SiO clumps found within the CND either<br />

had high enough velocity gradients or had experienced a sufficient<br />

decrease in angular momentum to spiral closer to Sagittarius A*<br />

www.yalescientific.org<br />

than would be otherwise possible. This process, called molecular<br />

cloud inspiraling, was thought to be part of what could foster<br />

stellar formation so close to a black hole.<br />

The team behind Peißker’s study sought to build upon this work.<br />

They compiled data on X3 spanning three decades from four<br />

different telescopes, including the Very Large Telescope in Chile, to<br />

better map out the X3 system and its surroundings. The team divided<br />

the X3 system into three components—designating the young stellar<br />

object as X3a and two neighboring thermal blobs as X3b and X3c—<br />

and collected data about nearby stars and gas clusters. The analysis<br />

helped the team confirm the star’s proximity to Sagittarius A* and<br />

better understand its origins by examining its characteristics.<br />

In addition to the accretion of the SiO gas clumps discussed in<br />

previous research, the team believes that rotating regions of dust<br />

and gas in the Galactic Center, called stellar disks, may also have<br />

been key to X3’s formation. The thickness of these disks would have<br />

been sufficient to lower the temperature within the region for star<br />

formation to be feasible, while simultaneously protecting the area<br />

from the black hole’s radiation.<br />

As they rotate, these stellar disks become dense enough to create<br />

massive gas clusters conducive to high-mass stellar formation. The<br />

team believes that one of these clusters, IRS 13, was instrumental<br />

to the formation of the X3 system. Based on the team’s data points,<br />

the timeline for this formation theory aligns with our current<br />

understanding of this region’s stellar history.<br />

Peißker was excited upon confirming X3’s proximity to Sagittarius<br />

A*, but joked that the process of discovery was far more prolonged<br />

than an ordinary surprise reaction. “For six months, I ran day-in and<br />

day-out simulations to fit the data points,” Peißker said. “Back then,<br />

my daughter demanded milk almost every three hours each night.<br />

So I woke up, gave baby milk to my daughter, and started simulations<br />

with the new parameters. I did this around the clock.”<br />

Peißker hopes to build upon this work in the future to learn<br />

more about how the mechanisms of stellar formation respond to<br />

unconventional situations, which could lay the groundwork for a<br />

richer understanding of star evolution and our universe at large. ■<br />

May 2023 Yale Scientific Magazine 27


FEATURE<br />

Bioelectronics<br />

CYBORG ZEBR AFISH<br />

BY NATHAN MU<br />

USING THE BODY TO GROW FLEXIBLE ELECTRODES<br />

The human body is a machine. At a<br />

fundamental level, it depends on<br />

electrical currents within cells and<br />

electrical signals between cells to function.<br />

So, in a sense, the body produces its own<br />

electricity. But what happens if this power<br />

gets unplugged? This is the problem that<br />

researchers have faced in trying to cure<br />

diseases such as Parkinson’s, Alzheimer’s,<br />

epilepsy, and depression. In the brain—<br />

where electrical signaling is paramount—<br />

any small "unplugging" can throw off the<br />

system of electrical currents and quickly<br />

lead to improper function. Without a way<br />

to fix an improper pattern of electrical<br />

signaling, that part of the brain will slowly<br />

lose its charge and fizzle out, leading to the<br />

visible symptoms of these diseases.<br />

A team led by organic bioelectronics<br />

researchers Xenofon Strakosas and<br />

Hanne Biesmans of Linköping University<br />

in Sweden may be on track to develop<br />

a viable solution to this problem. They<br />

have targeted this issue of restoring<br />

dysfunctional electrical pathways by<br />

harnessing the body’s chemistry to form<br />

an electrode, or electrical conductor<br />

that helps produce a current, within the<br />

IMAGE COURTESY OF UC SAN DIEGO<br />

Researchers have developed brain sensor implants<br />

that can detect electrical signals.<br />

brain. “The really cool thing about this<br />

electrode is that it is a soft polymer that<br />

forms in situ, or within the brain, unlike<br />

metal electrodes that are harsh and rigid,<br />

and require open skull surgery,” Biesmans<br />

said. Any implant in the human body<br />

that does not belong there runs the risk<br />

of causing inflammation and inducing an<br />

immune response that will try to fight the<br />

implant. Current standards for inducing<br />

artificial electrical currents in the brain,<br />

such as gold electrodes, are not optimal.<br />

Biesmans’ team’s primary goal was to<br />

develop a "softer" alternative that could be<br />

formed within the body.<br />

Their approach was to create a gel<br />

mixture that, once injected into the brain,<br />

could self-assemble into a polymer that was<br />

able to restore electrical activity. There’s a<br />

popular saying that "the answer you seek is<br />

within you," and that’s the advice that the<br />

researchers followed. Previous researchers<br />

at Stanford had used an outside solution—<br />

genetic modification—to produce soft<br />

electrodes. However, this pathway comes<br />

with its own problems when it comes to<br />

human application due to ethical concerns<br />

over modifying human DNA. “With our<br />

simple injectable gel, there’s no need for<br />

genetic modification. And in the long<br />

term, maybe there is also no more need for<br />

open skull surgeries,” Biesmans said.<br />

This gel cocktail concoction is composed<br />

of monomers, or building blocks, as well<br />

as enzymes that will be used to make the<br />

polymer electrode. The powerful part of<br />

this research is that it takes advantage of<br />

the enzymatic breakdown of two types<br />

of biological sugars found in the body to<br />

assemble these monomers into a polymer<br />

electrode. First, glucose or lactate—<br />

two types of sugars in the body—are<br />

converted into hydrogen peroxide by<br />

common enzymes known as oxidases.<br />

Next, hydrogen<br />

peroxide is used<br />

by horseradish<br />

peroxidase (HRP),<br />

a naturally<br />

occurring enzyme,<br />

to start the<br />

p o l y m e r i z a t i o n<br />

process. And that’s<br />

it—a simple, twostep<br />

process links<br />

together the monomer<br />

components from the<br />

injected gel to form a soft<br />

electrode directly in the body.<br />

But even the coolest products still<br />

need to be tested for quality, and that’s why<br />

Biesmans and her team came up with a set<br />

of seven criteria ranging from fluidity to<br />

biocompatibility and stability to assess the<br />

electrodes. The first test they ran assessed<br />

the effectiveness of their injected electrode<br />

gel on 0.6 percent agarose gels, which is a<br />

well-known model for simulating brain<br />

chemistry and conditions. “In the early<br />

stages of research, if you don’t know<br />

much, you don’t want to go straight to<br />

zebrafish or animal models because you<br />

don’t know what works yet,” Biesmans<br />

said. In this initial stage of testing, the<br />

researchers went through at least fifty to<br />

sixty different injectable electrode gels to<br />

find a few that were promising enough to<br />

continue working with. “Some gels were<br />

too thick and did not even make it into the<br />

agarose gels,” Biesmans said.<br />

The team then moved on to<br />

demonstrating the conductivity,<br />

28 Yale Scientific Magazine May 2023 www.yalescientific.org


Bioelectronics<br />

FEATURE<br />

stability, and biocompatibility of the<br />

gel and the formed electrode. It would<br />

have been ideal to test these long-term<br />

effects with zebrafish, but this was not<br />

possible. “Our ethical permits did not<br />

allow us to keep the zebrafish alive for<br />

more than three days, so we had to find<br />

a different way,” Biesmans said. Instead,<br />

the researchers used electrode arrays to<br />

test for electrical currents maintained by<br />

the electrode polymer. They also exposed<br />

the polymers to harsh sound energy and<br />

live cell conditions to ensure that the<br />

polymer would not degrade. Both tests<br />

showed excellent results and confirmed<br />

the stability of the gel.<br />

These tests showed that the gel performs<br />

well, but is it safe to use? This was the<br />

team’s next question and perhaps the<br />

trickiest because of the potency of glucose<br />

oxidase enzymes. These enzymes can<br />

quickly produce lots of hydrogen<br />

peroxide, which can kill cells at<br />

very high concentrations. “We<br />

had to find an optimal balance<br />

between lactate oxidase and<br />

HRP enzymes so that we could<br />

get rid of the hydrogen peroxide<br />

as fast as it was being produced,”<br />

Biesmans said. Finally, the team<br />

had a breakthrough and found<br />

that a twenty-seven to one ratio of<br />

HRP to lactate oxidase worked best. “We<br />

were finally able to tune the amount of<br />

hydrogen peroxide so that we are not<br />

creating more problems than we<br />

are fixing,” Biesmans said.<br />

The final hurdle for Biesmans<br />

and her team was to test<br />

their gel in two live models:<br />

zebrafish and medicinal<br />

leeches. In zebrafish, the<br />

gel was introduced in the<br />

tailfin first, followed by<br />

the brain and heart.<br />

The gel turns deep<br />

blue when successfully<br />

polymerized, and the team<br />

saw this beautiful color in all<br />

three locations. Their hard work<br />

had finally resulted in a working<br />

electrode, without noticeable<br />

side effects on the zebrafish.<br />

www.yalescientific.org<br />

One of Biesmans’ favorite experiments<br />

was soaking zebrafish hearts in the gel<br />

cocktail. “I really like that the polymer<br />

formed around the arteries, where<br />

you find glucose and lactate. It’s not<br />

covering the entire heart. That was a nice<br />

demonstration of the specificity of this<br />

gel,” she said.<br />

Leeches were another nice proof<br />

of concept for demonstrating the<br />

effectiveness of this polymer electrode<br />

since they are easy to visualize. “Leeches<br />

have one central nerve, and if you stimulate<br />

the nerve, it will contract immediately. So,<br />

you get instant visual proof of whether<br />

your stimulation worked,” Biesmans said.<br />

A key finding from the leech model was<br />

that the polymer electrodes produced a<br />

gentler, tissue-friendly current as opposed<br />

to the stronger, harsher current produced<br />

by gold electrodes.<br />

Even with the success of this initial<br />

experiment, there is still much work to<br />

be done. Biesmans and her research team<br />

plan to further optimize the current gel,<br />

test new versions of gels with different<br />

monomer building blocks, and introduce<br />

their current gel in mice models.<br />

Biesmans is also working on trying to<br />

induce a similar gel-based polymerization<br />

in single cells, as opposed to tissues.<br />

“Overall, we are working<br />

on building up this<br />

toolbox of<br />

monomers and<br />

techniques for so many<br />

different applications,” Biesmans said.<br />

These applications include treating<br />

various diseases requiring electrical<br />

stimulation by forming polymer<br />

electrodes at many different sites with<br />

disparate properties.<br />

This is just the beginning of exploring<br />

electrical patterns in the brain. While<br />

this team focused on restoring electrical<br />

activity, there are also projects such as<br />

Elon Musk’s Neuralink program that seek<br />

to use machines to interpret the meaning<br />

of the brain’s electrical signals. Perhaps<br />

this research will lead us towards a future<br />

of not just cyborg zebrafish, but cyborg<br />

humans that fully utilize the brainmachine<br />

interface. This makes organic<br />

bioelectronics a highly interdisciplinary<br />

field, and for Biesmans, this has been one<br />

of her favorite aspects of the work. “It’s<br />

interesting and fun to work with all these<br />

collaborators from different disciplines<br />

together. So, let’s see where it brings me,”<br />

Biesmans said. ■<br />

ART BY<br />

COURTNEY JOHNSON<br />

May 2023 Yale Scientific Magazine 29


FEATURE<br />

Palaeogenomics<br />

BY MATTHEW BLAIR<br />

ART BY MALIA KUO<br />

VACATIONING IN SPAIN<br />

HOW ANCIENT HUMANS ESCAPED THE ICE AGE<br />

Genetic testing platforms like<br />

23andMe and Ancestry.com<br />

have been in the spotlight for<br />

many years now. These testing programs<br />

have grown immensely popular, with<br />

some people finding long-lost relatives<br />

or discovering that a historical figure is<br />

somewhere in their family tree.<br />

But for those living over forty thousand<br />

years ago, unfortunately, no such genetic<br />

testing was available. Those early humans<br />

lived without ever knowing their full<br />

genetic history. Some early humans<br />

perhaps wholly missed the opportunity to<br />

gloat that they were related—somewhere<br />

in their bloodline—to the first Homo<br />

sapiens to discover fire.<br />

Now, however, He Yu of Peking<br />

University in Beijing, China and her<br />

team of researchers have constructed a<br />

genetic narrative for these early humans.<br />

Their study is the most comprehensive<br />

examination of certain hunter-gatherer<br />

groups living in Europe around the Ice<br />

Age. It reveals important information<br />

about the mixing between different<br />

groups and their migratory patterns.<br />

This study shines a light on the genetic<br />

differences and similarities of different<br />

hunter-gatherer groups and focuses<br />

especially on how these groups survived<br />

the Last Glacial Maximum (LGM), which<br />

was the most intense period during the<br />

last Ice Age.<br />

The group’s study examined where<br />

hunter-gatherer groups migrated in<br />

order to evade the massive glaciers and<br />

blisteringly cold temperatures moving<br />

across the globe during the LGM, which<br />

lasted from twenty-five thousand to<br />

nineteen thousand years ago. The LGM is<br />

particularly interesting to study because<br />

researchers believe it created a large<br />

migration of hunter-gatherer groups.<br />

Prior studies have found that the LGM<br />

pushed hunter-gatherer groups to move<br />

into southern latitudes, specifically the<br />

Iberian peninsula and southern France,<br />

with some studies also suggesting that<br />

hunter-gatherers could have moved into<br />

the Italian peninsula, the Balkans, and<br />

the southeastern European Plain.<br />

It is impossible to determine where<br />

groups may have moved during the<br />

LGM without having a snapshot of their<br />

locations and genetic makeups before and<br />

after this period. As such, the study spans<br />

from thirty-five thousand to five thousand<br />

years ago, covering before, during, and<br />

after the LGM. “This paper focuses on<br />

where people traveled to find refuge and,<br />

after the LGM, expanded again to form<br />

the later population structure,” Yu said.<br />

Using mostly bones, teeth, and other<br />

materials that could contain genetic<br />

information, Yu and her research team<br />

created new genomic information for<br />

hunter-gatherer groups that are now<br />

extinct. It is easy to send in your saliva<br />

sample to a genetic testing company site,<br />

but researchers had to meticulously comb<br />

through paleogenomic data to construct<br />

a very large and complex family tree. In<br />

this paper, 356 ancient hunter-gatherer<br />

genomes were analyzed, 116 of which were<br />

newly reported by researchers across the<br />

globe in fourteen countries throughout<br />

western and central Eurasia.<br />

Once the researchers confirmed that<br />

these samples contained genetically viable<br />

information, they began the process of<br />

genetic testing. The first, most crucial,<br />

step in this process is to extract the<br />

DNA and sequence the genome. Often,<br />

however, sequencing the genome is the<br />

simplest part. “When we get the data, we<br />

have a lot to do with it. We first examine<br />

their genetic differentiation, trying to<br />

see what samples look more similar and<br />

which are more dissimilar. Specifically,<br />

we focus on the alleles and other genetic<br />

information that could be shared between<br />

some individuals and not others,” Yu<br />

said. Alleles are the genetic information<br />

that could potentially be shared between<br />

individuals—the genetic information that<br />

could contribute to physical traits like<br />

blue eyes or brown hair. This process of<br />

analyzing these alleles and other genetic<br />

information involves a great deal of<br />

high-level statistical analysis and other<br />

methods of biological comparison.<br />

This data analysis allows researchers<br />

to test specific hypotheses about the<br />

movement and mixing of hunter-gatherer<br />

groups. There are many different ideas<br />

about where a group could have gone<br />

and which other hunter-gatherers they<br />

30 Yale Scientific Magazine May 2023 www.yalescientific.org


Palaeogenomics<br />

FEATURE<br />

might have<br />

e n c o u n t e r e d<br />

along the way, but<br />

this method of data<br />

collection and analysis can<br />

quantitatively prove or disprove<br />

these conclusions.<br />

The researchers also considered a<br />

multitude of other factors, including<br />

the radiocarbon dates of the materials,<br />

so that they can pinpoint the age<br />

of the samples and discover other<br />

archaeological information. Simply,<br />

radiocarbon dating is the process by<br />

which researchers analyze the amount<br />

of radioactive carbon-14 left in a sample<br />

in order to measure its age. Further,<br />

cultural information about specific<br />

hunter-gather groups, such as knowledge<br />

about their mortuary practices or the<br />

types of weaponry they commonly used,<br />

allowed the researchers to make<br />

increasingly sound conclusions about the<br />

movements of certain hunter-gatherer<br />

groups and their possible relations to<br />

other groups.<br />

With this research, Yu and her team of<br />

researchers have established a genomic<br />

study of remarkable depth and breadth.<br />

By drawing on multitudes of biological<br />

and historical information, they created<br />

a firmly-rooted “family tree” for huntergatherer<br />

groups.<br />

When working with a data set that is so<br />

ancient, many challenges can arise. The<br />

majority of the time, the samples used<br />

usually come from bones or teeth. These<br />

physical samples last through the ages<br />

which makes them strong candidates<br />

for DNA extraction. In especially old<br />

samples, however, the DNA degenerates<br />

and is poorly preserved. “The samples<br />

that are reported, of course, are not the<br />

only samples that we have processed.<br />

There were various samples that did not<br />

produce enough DNA and some which<br />

had none at all, failing during the DNA<br />

extraction process,” Yu said.<br />

Even when a sample does<br />

produce enough DNA, that data<br />

must be observed with a critical eye. As<br />

these samples have often been studied by<br />

multiple parties and transported across<br />

the globe, the risk for contamination is<br />

high. “For many samples, we also had a<br />

hard time trying to detect and confirm if<br />

they are contaminated or not. Further, if<br />

samples were found to be contaminated,<br />

we then had to go through the process<br />

of separating the DNA of that specimen<br />

from its contaminants so that we could<br />

get real information,” Yu said.<br />

This study showed that huntergatherer<br />

groups flocked to western and<br />

southwestern Europe to escape the Ice<br />

Age. “It was always assumed that the<br />

Iberian Peninsula was a refuge during<br />

the Ice Age, but this is the first time we<br />

genetically confirmed that there is really a<br />

human population—with the same genetic<br />

ancestry found earlier in other regions of<br />

Europe—living in that area,” Yu said. This<br />

is a powerful confirmation that paints a<br />

clearer picture of the survival, migration,<br />

and mixing of hunter-gatherer groups.<br />

But researchers still have questions,<br />

especially about the importance of another<br />

region as a refuge during the Ice Age: the<br />

Italian Peninsula. In this region, there<br />

were massive genomic changes before<br />

and after the Ice Age, so researchers<br />

cannot make a succinct conclusion on<br />

whether or not it was a refuge based<br />

on DNA evidence alone. These<br />

regions saw a huge genomic<br />

turnover, with distinct genetic populations<br />

before and after the LGM. “Genetic<br />

information could help us to answer or<br />

confirm some points, but it alone cannot<br />

confirm them all. It is important in these<br />

sorts of studies to combine information<br />

from different sources and evidence from<br />

different disciplines,” Yu said.<br />

History itself is expansive, and trying to<br />

capture the movement of many different<br />

groups over tens of thousands of years is an<br />

exceedingly difficult task, but researchers<br />

like Yu and her team are embarking on this<br />

journey through time to reveal important<br />

information about how our earliest<br />

ancestors survived and how all of us are<br />

here today. As we move forward and learn<br />

more about our personal genomic histories<br />

through popular testing platforms, we can<br />

appreciate the work they are doing to<br />

capture the genomic ancestry of<br />

humans across the world. ■<br />

www.yalescientific.org<br />

May 2023 Yale Scientific Magazine 31


FEATURE<br />

Immunology<br />

PLANT-ANIMAL<br />

HYBRIDS<br />

PROTECTING PLANTS<br />

WITH ANIMAL ANTIBODIES<br />

BY SAMANTHA LIU<br />

ART BY KARA TAO<br />

Plant-animal hybrids are here, and<br />

they are exactly what they sound<br />

like. In the Sainsbury Laboratory<br />

in Norwich, UK, wild tobacco plants have<br />

been engineered to produce "pikobodies,"<br />

synthetic proteins that can recognize and<br />

attack pathogens expressing fluorescent<br />

proteins. These pikobodies are made<br />

by taking rice-derived receptors and<br />

swapping in antibody<br />

f r a g m e n t s<br />

originating<br />

from<br />

camelid mammals, specifically llamas and<br />

alpacas. In a proof-of-concept study—<br />

carried out by postdoctoral scientist Jiorgos<br />

Kourelis of the group headed by Sophien<br />

Kamoun—the team discovered that these<br />

pikobody-producing tobacco plants could<br />

successfully stave off viral invaders.<br />

This discovery arrives at a crucial<br />

moment: in the past year alone, wars,<br />

climate change, and trade routes in flux<br />

have ferried pathogens around the<br />

globe in dangerously unprecedented<br />

ways. Meanwhile, as a wheat<br />

blast devastates crop yields<br />

in Africa and Asia,<br />

and scientists<br />

sound<br />

alarm<br />

bells to food security worldwide, protection<br />

against plant diseases is more important<br />

than ever.<br />

While current mechanisms of disease<br />

resistance in agriculture are mostly<br />

chemical (think pesticides, fungicides,<br />

and a host of other -ides), with pikobodies,<br />

genetic treatments may replace our reliance<br />

on chemical treatments. “We can generate<br />

made-to-order resistance genes against<br />

virtually any pathogen,” Kourelis said.<br />

The idea is certainly an imaginative if<br />

not unbelievable one, almost like science<br />

fiction. But it didn’t originate out of the blue.<br />

Scientists have long been interested in the<br />

integrated domain (ID) of plant receptors,<br />

which is responsible for recognizing<br />

pathogen effectors and triggering an<br />

immune response. In one key study by<br />

French scientist Stella Cesari, engineering<br />

the ID of Pik-1—a receptor that normally<br />

attacks fungal invaders—could allow<br />

tobacco plants to gain specificity and bind<br />

new sequences. Ever since then, Kamoun<br />

has wondered if he could engineer Pik-1 to<br />

recognize other pathogens.<br />

The second piece of the puzzle—<br />

introducing the animal antibody—came<br />

four years ago, with Kourelis’ arrival at<br />

the lab. During a lab meeting, Kourelis<br />

proposed “A General Solution for Plant<br />

Pathology”—a title which, of course, caught<br />

the attention of everyone in the room.<br />

As Kourelis noted, one problem with<br />

plant immune defenses is that they lack<br />

mobile or specialized cells for attacking<br />

32 Yale Scientific Magazine May 2023 www.yalescientific.org


Immunology<br />

FEATURE<br />

viruses, unlike animals. Plants instead<br />

rely on nucleotide-binding, leucine-rich<br />

receptors (NLRs), which can recognize<br />

diverse pathogen components and<br />

activate the immune response. But NLRs<br />

are limited in what they can recognize—<br />

and their scope is hard-coded by DNA,<br />

which cannot evolve as fast as rapidlychanging<br />

viruses.<br />

In contrast, mammals can create and<br />

proliferate specific antibodies for virtually<br />

any virus they are exposed to. Not only do<br />

these antibodies target, mobilize, and kill<br />

viral particles, but the animal also retains<br />

them well after the infection, in case of<br />

future threats—the same principle which<br />

guides vaccines. “Basically, you could<br />

potentially build a disease resistance gene<br />

against any plant pathogen by exploiting<br />

the adaptive immune system of animals,”<br />

Kamoun said.<br />

Enter the llamas. Kourelis suggested<br />

taking camelid mammal nanobodies—<br />

the fragment of antibodies which actually<br />

binds to the pathogen—and fusing them<br />

to Pik-1. In this way, plants’ integrated<br />

domains could serve as a scaffold to trigger<br />

the immune response, while mammalian<br />

antibodies could let them recognize a host<br />

of other pathogens.<br />

To turn their concept into practice,<br />

Kourelis still needed a framework for<br />

where and how to engineer the receptors.<br />

His answer was bolstered by an earlier<br />

project by colleague and Ph.D. student<br />

Aleksandra-Ola Bialas, who investigated<br />

how the Pik-1 receptor arose fifty million<br />

years ago. Critically, by looking at the<br />

evolutionary origins of Pik-1, Bialas’s<br />

work helped delimit the boundaries of the<br />

domain that Kourelis was so interested in.<br />

“So fifty million years ago, nature<br />

actually did this engineering and<br />

integrated the domain into this [Pik-<br />

1] receptor,” Kamoun said. “And if you<br />

understand how nature has done it, you<br />

could repeat it in the lab.<br />

Even with Bialas’s contribution, the<br />

process to pare down potential candidates<br />

was arduous. It required iterations of<br />

revisiting basic science, tweaking existing<br />

combinations, and, at some point, sheer<br />

brute force, Kourelis recalled. “Sometimes<br />

we were like, ‘Let's drop in as many<br />

nanobodies as we can and see if some of<br />

them work,’” Kourelis said. “‘And then, if a<br />

Transgenic tobacco plants serve as the model organism for pikobody testing.<br />

few work, even if they don't work great, let's<br />

understand what's going on there.’”<br />

Eventually, he engineered eleven<br />

pikobody candidates to recognize<br />

fluorescent proteins. They were vetted<br />

for autoimmune responses and cell death<br />

responses until only four pikobodies<br />

remained. After introducing a live Potato<br />

virus X, which was engineered to express<br />

fluorescent proteins, two pikobodies were<br />

found to halt viral spread substantially.<br />

And if used together, these two pikobodies<br />

proved to be even more effective.<br />

Now, Kourelis and Kamoun are looking<br />

toward future applications for pikobodies.<br />

They are both enamored with the potential<br />

of “designer” domains, with each plant<br />

tailored with pikobodies against diseases<br />

that might threaten it. They even speculated<br />

that, with advanced artificial intelligence,<br />

computers may someday design the<br />

binding domains, circumventing the need<br />

for antibodies altogether.<br />

For Kourelis, one of the challenges lies<br />

in accounting for—and staying ahead<br />

of—pathogen evolution. As he looks to<br />

apply his model and develop a toolkit of<br />

new receptors, he hopes to identify target<br />

sequences that will be long-lasting. If they<br />

can pick target sequences that are unlikely<br />

to change, then the pathogen is less likely<br />

to evolve to resist that receptor. “Then<br />

IMAGE COURTESY OF PIXABAY<br />

again, I like to say, ‘Never bet against the<br />

pathogen,’” Kamoun said.<br />

In the book-lined office from which<br />

Kamoun and Kourelis take this Zoom<br />

interview, it is not difficult to envision<br />

them collaborating in a laboratory.<br />

Kourelis fields a question. Kamoun<br />

modifies Kourelis’s answer, then raises<br />

another point, which reminds Kourelis of<br />

another idea. Even as they talk to me, their<br />

conversation with each other never ceases.<br />

Their dialogue—revising, rephrasing,<br />

circling—reflects the cycles it took Kourelis<br />

to get to his top-performing pikobodies.<br />

But this is their process and, perhaps,<br />

the reason they are successful. Kourelis<br />

emphasized multiple times that they<br />

regard themselves as scientists first, and<br />

engineers second. No matter what sciencefiction<br />

universe plant-animal hybrids and<br />

pikobodies seem to resemble, for Kourelis<br />

and Kamoun, these ideas are firmly rooted<br />

in listening to what already exists—to<br />

plants, to other scientists, to each other—<br />

before they create something new.<br />

“There’s a more fundamental<br />

understanding in seeing how, in nature,<br />

these proteins have evolved, how these<br />

domain integrations have happened,”<br />

Kourelis said. “You have to understand<br />

before you can take the next step. You have<br />

to understand nature by making it.” ■<br />

www.yalescientific.org<br />

May 2023 Yale Scientific Magazine 33


UNDERGRADUATE PROFILE<br />

CHARNICE HOEGNIFIOH<br />

YC ’24<br />

BY EMILY SHANG<br />

A<br />

double major in Classical Civilizations and Molecular<br />

Biophysics and Biochemistry, Charnice Hoegnifioh (BF ’24)<br />

is studying the science behind ancient makeup and skincare<br />

artifacts. Hoegnifioh was recently awarded the Edward A. Bouchet<br />

Fellowship and the $35,000 Beinecke Scholarship, which will support<br />

her academic research and post-graduate studies in the medical<br />

humanities, respectively.<br />

Hoegnifioh fell in love with biochemistry in<br />

high school. She especially enjoyed conducting<br />

experiments involving spectroscopy, the study of<br />

the emission and absorption of electromagnetic<br />

radiation by matter. After participating in<br />

the MIT Introduction to Technology,<br />

Engineering, and Science program<br />

in high school, she realized that she<br />

wanted to devote her undergraduate<br />

studies to biophysics. At the same<br />

time, she loved Latin, and her<br />

passion for Classics was cemented<br />

by a school trip to Greece. Ultimately,<br />

she found that “following her passion”<br />

at Yale meant loading up on five credits<br />

of Classical Civilization courses in her first<br />

year, while also researching ultrafast protein<br />

folding in the Davis Lab. She decided to pursue<br />

a double major and focus her time on honing her<br />

skills in these two areas.<br />

One of Hoegnifioh’s most recent classes applied spectroscopy and<br />

isotopic dating—the analysis of materials based on the decay rates of<br />

unstable elemental isotopes—to examine seals from the ancient Near<br />

East. Traditionally, these seals, which were ubiquitous in Mesopotamia<br />

and used for administrative and decorative purposes, were dated based<br />

on their iconography since their styles could be traced back in time.<br />

Hoegnifioh explained that studying the seals’ isotopic proportions can<br />

allow researchers to determine their geographical origins. “By looking<br />

at isotopic ratios of materials, you can differentiate whether a material<br />

or mineral came from Scandinavia or the Middle East,” Hoegnifioh said.<br />

As an Edward A. Bouchet Fellow, Hoegnifioh will study abroad in<br />

Germany, Greece, Italy, the United Kingdom, and France this summer<br />

and visit archaeological sites to research ancient cosmetic artifacts and<br />

their effects on healing. One artifact she’s particularly excited to see is an<br />

ointment tin from ancient Rome, excavated by the Museum of London<br />

twenty years ago, that still shows the preserved<br />

fingerprints of the original owner. Beyond<br />

the Museum of London,<br />

Hoegnifioh will go to the<br />

archeological museum in<br />

Frankfurt to view<br />

their exhibition<br />

of paint pots. “[Cosmetics] were posited as healing outward feminine<br />

flaws but also inward flaws in women. So I’ll be going to some healing<br />

sanctuaries and learning more about healing authority and what<br />

ingredients were thought [to have] curative properties,” Hoegnifioh said.<br />

Her work will culminate in her senior thesis, tentatively titled<br />

“Remedies for Roman Beauty: Curative Cosmetics during the<br />

Roman Empire.” Hoegnifioh’s interest in cosmetics<br />

began during her summer internship at Harvard,<br />

where she conducted a research project on the<br />

painful and poisonous aspects of beauty as<br />

a first-year student. Through her research,<br />

she learned that one of the most popular<br />

misconceptions about beauty routines<br />

in the classical world is that the ancient<br />

Romans unknowingly used lead<br />

within the cosmetic pigment. “It<br />

turns out that the Romans were<br />

actually aware that white lead<br />

was extremely toxic, as there was<br />

a treatise written that lead shouldn’t<br />

be used in pipes or buildings because it<br />

will lead to poisoning. But women were<br />

still being hurt, so I wanted to investigate<br />

why these societal standards were coming<br />

before women’s health,” Hoegnifioh said.<br />

Hoegnifioh cites multiple major influences in<br />

PHOTOGRAPHY BY HANNAH HAN<br />

her journey throughout Yale, the first being her<br />

Latin professor from her first year, Irene Peirano Garrison, who<br />

left Yale to teach at Harvard but remained her close confidant and<br />

advisor. Peirano Garrison advised Hoegnifioh to pursue a Ph.D.<br />

in the humanities and guided her through an ongoing graduate<br />

project on makeup in antiquity. “Her impact on my life is<br />

beyond words. I would not be where I am without her and<br />

her motivational presence in my life,” Hoegnifioh said.<br />

She also cites Jessica Lamont, an assistant professor of<br />

Classics, and Milette Gaifman, the Andrew Downey<br />

Orrick Professor of Classics and History of Art, as<br />

other advisors who have guided her through her<br />

undergraduate studies.<br />

When asked what advice she would give to<br />

underclassmen, Hoegnifioh emphasized that double<br />

majoring in two disparate fields is achievable given<br />

proper preparation, and she hopes that no one is<br />

deterred because of the prerequisite courses. “Planning<br />

is key, but don’t hold yourself to super strict standards<br />

because things change. So allow yourself that flexibility,”<br />

Hoegnifioh said. “Remember that imposter<br />

syndrome is real, but you are talented, and if<br />

you’re at Yale, you definitely deserve to be here.” ■<br />

34 Yale Scientific Magazine May 2023<br />

www.yalescientific.org


ALUMNI PROFILE<br />

AMYMARIE BARTHOLOMEW<br />

YC ’13<br />

BY WILLIAM ARCHACKI<br />

This June, graduates from Yale’s Class of 2013 will flock back to<br />

campus for their ten-year reunion. For Amymarie Bartholomew<br />

(YC ’13), the trip will be as simple as a walk down Science<br />

Hill from her new lab at Kline Chemistry Laboratory. Appointed an<br />

assistant professor in January of this year, Bartholomew now works<br />

in the chemistry department alongside many of the faculty members<br />

she had as teachers and mentors during her time as an undergraduate.<br />

Back and better than ever, Bartholomew is a doctorate-wielding<br />

chemist whose work focuses on synthesizing stimuli-responsive<br />

inorganic materials. The graduate-level course she teaches, “Molecular<br />

Materials,” reflects the aims of her research: to produce materials that<br />

change their physical, magnetic, and electrical properties in response<br />

to interactions at the molecular level. For instance, the absorption of<br />

light might change the way bonds form, or an increase in temperature<br />

might alter the way electrons behave in a magnetic field.<br />

Bartholomew thinks of her work as a search for new ways to apply<br />

these tiny molecular changes to the creation of useful materials.<br />

“I’ve always had a lot of ideas for things to synthesize and things to<br />

try, and I think in chemistry—as well as in<br />

other fields—it’s really about just trying<br />

things,” Bartholomew said. “Being<br />

able to see which of my ideas hold<br />

promise and which of them are able<br />

to move forward—I think that’s<br />

really exciting.”<br />

One project the lab group is<br />

working on seeks to use the<br />

molecule azobenzene to<br />

produce electricity from<br />

sunlight. For a long time,<br />

scientists have known<br />

that azobenzene can switch<br />

between two shapes:<br />

one that bends back<br />

on itself and one that is<br />

long and straight. When<br />

high-energy ultraviolet<br />

light strikes azobenzene<br />

crystals, they tend to<br />

flex and deform as their<br />

many constituent atoms<br />

switch between the two shapes. Bartholomew’s<br />

research is taking this behavior of azobenzene to<br />

new heights. By creating larger molecules that contain<br />

multiple azobenzene components bonded at special angles,<br />

Bartholomew and her collaborators have produced a<br />

material that rotates around a central axis when<br />

exposed to visible light. Under a microscope,<br />

crystals of this material appear to continuously<br />

www.yalescientific.org<br />

PHOTOGRAPHY BY HANNAH HAN<br />

roll like long axles, performing the kind of mechanical work that<br />

can generate electricity. Bartholomew hopes that this single-step<br />

conversion from solar energy to mechanical work will provide a<br />

starting point for more efficient solar power.<br />

Bartholomew also focuses on the kinds of stimuli-responsive<br />

changes that could pave the way for new nanoscale electronics.<br />

Like the azobenzene complexes, most of Bartholomew’s materials<br />

are crystalline in structure. Not only does the ordered pattern of<br />

crystals make for useful physical properties, but it also provides<br />

chemists with an insight into how and why stimuli responses occur.<br />

“If you ever need to find me, I’m probably trying out crystals on the<br />

diffractometer in the crystal lab,” Bartholomew said. “I love being<br />

able to make something, crystallize it, and then use those crystals<br />

to determine the three-dimensional structure of what I’ve made.”<br />

The research that Bartholomew has carried out in her first months<br />

as a professor has largely taken place thanks to generous colleagues<br />

who have lent their research spaces to her. After all, it takes time<br />

to acquire all the equipment necessary to run a cutting-edge<br />

chemistry lab. Bartholomew’s own space is just a short<br />

walk from the lab of chemistry professor Nilay<br />

Hazari, where Bartholomew conducted research<br />

as an undergraduate. Bartholomew explained<br />

that Hazari acts as a model for her now that<br />

she has the responsibility of mentoring.<br />

Bartholomew also credited Professor<br />

Kurt Zilm, the instructor of<br />

her undergraduate physical<br />

chemistry class, for showing<br />

her how to teach chemistry.<br />

“I think pedagogically I<br />

definitely took a lot from<br />

that class—hopefully.<br />

You’ll have to ask the<br />

graduate students in my<br />

class now if that’s the case,<br />

but that’s the aim anyway,”<br />

Bartholomew said.<br />

Now with the classroom<br />

and the lab under her control,<br />

Bartholomew is putting her own<br />

creativity to the test. Fortunately,<br />

Bartholomew has an endless stream of fresh<br />

ideas in her niche of synthetic chemistry. “I<br />

sit at home and think of new things we should<br />

try to make, and I have to sketch them out at<br />

like ten p.m. and send myself a weird email<br />

with two sentences of an idea,” Bartholomew<br />

said. To handle the strange world of molecular<br />

materials, there may be no better approach. ■<br />

May 2023 Yale Scientific Magazine 35


MEASURE FOR MEASURE<br />

BY HENRY CHEN<br />

IMAGE COURTESY OF MEASURE FOR MEASURE<br />

SCIENCE<br />

How would you rank the following: Friends, The Office, and Modern<br />

IN<br />

Family? How do you—and other people—differentiate between your<br />

favorite shows, books, and podcasts? Is there a universally defined<br />

scale? What are some factors we use to compare? These are all questions that<br />

“Measure for Measure” seeks to explore.<br />

Run by the organization Ministry of Ideas and co-hosted by Liya Rechtman<br />

and Andrew Middleton, “Measure for Measure” is a limited podcast series<br />

that investigates a different form of measurement in our daily lives. The<br />

nine episodes, which range from nine to twenty-five minutes in length, are<br />

perfect to squeeze in during a walk between classes. The podcast covers topics<br />

spanning the Scoville spice scale, used to measure the pungency of chili<br />

peppers, to star “heartbeats,” which are pulses that cause a star to expand and<br />

contract, leading to variations in brightness. Most importantly, each episode<br />

tries to answer the overarching question: why has measurement been crucial<br />

throughout human history?<br />

For example, in episode two, Rechtman talks about how the Talmud, a central<br />

Judaic text, contains a number of references to measurements, like how much<br />

matzah to eat during Passover, that were based on the size of other foods, like<br />

olives. Because olive sizes have varied over the centuries, many Jewish people<br />

today have tried to update the medieval measurement to determine how much<br />

matzah to eat. The story of the olive is one of unity across time—how even<br />

though Jewish people are separated from their ancestors by thousands of years,<br />

they can still celebrate in the same way, following similar cultural guidelines.<br />

Importantly, each episode presents a narrative about using measurement as a<br />

way for us to (re)connect with the rest of the world—both past and present.<br />

As I made my way through the series, it became clear where each of the cohosts’<br />

passions came into the episodes. Rechtman is a Jewish climate activist,<br />

while Middleton is a cartographer and ocean enthusiast. As a result, each episode<br />

was a science lesson infused with niche, thoroughly interesting historical and<br />

cultural facts—an engaging format that sparks questions about the intersection<br />

between the humanities and science. For instance, in episode three, we learn about<br />

the Mohs scale for categorizing the hardness of rocks and how it was created by<br />

the Habsburg Empire to distinguish itself from competing empires and increase<br />

national unity. These stories reinforce the idea that measurement isn’t restricted<br />

to the International System of Units we use in chemistry class. Instead, it extends<br />

far beyond, into almost every facet of human life.<br />

At the end of the nine episodes, I still haven’t found a definitive scale to rank<br />

podcasts, but I have learned the importance of tools for measurement in our lives<br />

and how they turn a continuous reality with infinite possibilities into discrete<br />

categories—and maybe that’s the point. For its combination of historical facts,<br />

scientific trivia, and broad cultural trends, I’m placing “Measure for Measure”<br />

in the category of “highly recommended.” ■<br />

T<br />

36 Yale Scientific Magazine May 2023 www.yalescientific.org


THE DARKNESS MANIFESTO<br />

You’ve probably flown over a city at night and noticed the bright glow of<br />

lights staring back at you through the airplane window. As intriguing<br />

and surreal as it feels to see such a sight, these lights are disrupting<br />

the behavioral patterns and circadian rhythms of many organisms across<br />

the globe, from insects and bats to bioluminescent creatures and humans. In<br />

his newly released book, The Darkness Manifesto, Johan Eklöf describes the<br />

myriad consequences related to light pollution and urges readers to defend<br />

the darkness.<br />

The majority of nature’s activities, such as mating and pollination, occur<br />

at night because eighty percent of all organisms are nocturnal. Humans are<br />

diurnal organisms (active during the day) and, as a result, have resorted<br />

to artificial light to extend our activities into the night. Eklöf echoes the<br />

claims that we have entered a new era: the Anthropocene, in which humans<br />

have had a critical impact on the Earth’s ecosystems. In particular, he argues<br />

that man-made sources of light are disrupting Earth’s natural rhythms by<br />

generating light pollution.<br />

Eklöf devotes several chapters to describing the ways in which light<br />

pollution has thrown off the reproductive cycles of organisms across the<br />

planet. For instance, he claims that the pollination rate of some plants like<br />

apple trees has slowed down because moths, which serve as pollinators, get<br />

easily confused by artificial sources of illumination. For animals like our<br />

beloved friend Nemo, the consequences of light pollution are as severe as eggs<br />

failing to hatch since clownfish larvae rely on the darkness to signal when it<br />

is time to break free from their sacs. Without complete darkness at night, the<br />

behavioral patterns of organisms are becoming increasingly out of tune, and<br />

as a result, the ecosystems they inhabit are being destroyed.<br />

But it isn’t just plants and animals that are affected. We humans are facing<br />

serious consequences as well. Because humans aren’t nocturnal, we rely on<br />

our natural sleep cycles to rest. But true rest is difficult to achieve when we are<br />

using our phones too late into the night. Blue light from our phones tricks our<br />

brains into thinking it is still daytime, so we produce insufficient levels of our<br />

natural sleep hormone, melatonin, making it difficult to fall asleep. Similarly,<br />

Eklöf states that people who work night shifts are at a higher risk of hormonal<br />

cancers such as breast and prostate cancer. We can prevent a multitude of<br />

THE<br />

SPOTLIGHT<br />

serious health conditions by restoring our natural circadian rhythms and<br />

avoiding light at night.<br />

In his manifesto at the end of the novel, Eklöf calls upon readers to cherish<br />

and learn more about the darkness due to its importance in our behavioral<br />

patterns. Some countries, like France, are already moving towards decreased use<br />

of artificial light at night, and Eklöf hopes that more countries will follow suit.<br />

“The darkness is not the world of humans. We’re only visitors,” Eklöf reminds<br />

readers. It’s not too late to change our habits and start protecting the darkness. ■<br />

BY FAITH PENA<br />

IMAGE COURTESY OF WALLPAPER FLARE<br />

www.yalescientific.org<br />

May 2023 Yale Scientific Magazine 37


COUNTERPOINT<br />

QUANTUM<br />

BY MATTHEW DOBRE<br />

CRYPTOGRAPHY<br />

Encrypting data in holograms composed of corkscrews of light<br />

In 1933, Nobel Prize-winning chemist Sir William<br />

Bragg said, “Light brings us the news of the<br />

Universe.” Though it would take decades before<br />

scientists better understood the properties of light,<br />

researchers today are devising ways to utilize this<br />

resource to store information by uniting information<br />

theory and quantum mechanics, a subfield of physics<br />

that governs the behavior of photons, or light particles.<br />

Among the general public, anything that includes the<br />

word “quantum” elicits a degree of awe. Even Einstein<br />

was troubled by one of the theoretical implications of<br />

quantum mechanics, which he called “spooky action<br />

at a distance.” Today, Einstein’s boogeyman is called<br />

entanglement. When two particles are entangled, their<br />

quantum states, which may include properties like<br />

geometric orientation, angular momentum, and energy,<br />

are inextricably linked. A change in the state of one<br />

particle will immediately affect its twin. For example,<br />

consider a pair of entangled mittens: one is given to a<br />

lab assistant named Bob, and the other to his partner,<br />

Alice. No attempt is made to observe either mitten. Bob<br />

is then sent to a neighboring solar system. Up to this<br />

point, nobody in the universe knows the handedness of<br />

either Alice’s or Bob’s mittens. In fact, by the postulates<br />

of quantum mechanics, their handedness will be<br />

indeterminate until they are observed. If this experiment<br />

was repeated many times, it would reveal that when<br />

Alice observes her mitten, she will have a right-handed<br />

mitten half the time, and a left-handed mitten the other<br />

half. Eerily, Bob’s mitten will instantaneously acquire<br />

the opposite handedness, even though he’s two million<br />

light years away from Alice.<br />

These same principles of entanglement have been<br />

used to send data over thin air. In 2015, a research<br />

team in Vienna transmitted information by changing<br />

the relative angular momentum, or “twistiness,” of<br />

entangled pairs of photons. In quantum mechanics,<br />

angular momentum can only take on certain values<br />

called discrete quantities, separated by a constant ‘step<br />

size’. These entangled particles stored information by<br />

acting analogously to computer bits, which can only<br />

have a value of zero or one. In the experiment, each twist<br />

served as an alternative channel of communication,<br />

enabling ultra-high-speed data transmission.<br />

A group of physicists from the Beijing Institute of<br />

Technology (BIT) recently expanded on this research<br />

to create an unprecedented storage system. Instead of<br />

transmitting information via distinct light channels,<br />

they stored several unique data sets at a time by creating<br />

holograms made of entangled photon pairs. Though<br />

holograms seem to be a quintessential element of<br />

science fiction, they already have applications in<br />

everyday life. Used as a security feature in credit<br />

cards, passports, and banknotes, holograms are stacks<br />

of slightly misaligned images that are difficult for a<br />

computer to read. The physicists generated holograms<br />

made of twisted, entangled photon pairs by using<br />

β-barium borate crystals to manipulate the relative<br />

angular momentum between the particles, creating<br />

corkscrew patterns of light that resemble rotini pasta.<br />

To prove their setup worked, the researchers encoded<br />

words in the holograms and used twisted light to<br />

reconstruct the data by measuring the coincidence<br />

between the particles’ angular momentums.<br />

By increasing the number and diversity of twists<br />

in a single hologram, the system securely encrypted<br />

information since the odds of guessing the degree and<br />

direction of the twisted light’s path became very low. For<br />

instance, seven distinct twists, which is a relatively small<br />

system, led to millions of potential combinations.<br />

Many quantum technologies are sensitive to noise.<br />

However, the researchers asserted that entanglement<br />

can diminish the effect of classical noise sources, which<br />

include mechanical vibrations and thermal fluctuations.<br />

Thus, the decrypted output was of a higher quality<br />

compared to other similar systems.<br />

This technology, however, is still in its infancy.<br />

Utilizing six forms of entangled light, the group was<br />

able to decode an image of the acronym “BIT” by<br />

measuring the orbital angular momentum states of the<br />

particles over the course of twenty minutes, which is far<br />

from practical. Fortunately, the group is optimistic that<br />

these difficulties can be overcome with improvements<br />

in quantum technology. Though holographic data<br />

storage is still in a nascent stage, today’s scientists<br />

are utilizing techniques that the founders of modern<br />

physics laid the groundwork for—but may not have<br />

even understood. ■<br />

38 Yale Scientific Magazine May 2023 www.yalescientific.org


Wrought into a cycle,<br />

carbon schleps from one stop<br />

to the next.<br />

Perhaps I recall it<br />

swept along the atmosphere, or<br />

gathered by the ground.<br />

But in this primordial painting,<br />

lumbering green bacteria<br />

nose for warmth in the ocean,<br />

their cellular frames tousling the tides.<br />

Eventually, they dissolve<br />

like salt, and carbon stretches<br />

down to retire under the sand. And in<br />

this dizzying deepsea, the muddy<br />

seafloor, slumbering beneath<br />

carbon’s gray lines like a shutter<br />

over the dark, unsheathes<br />

the largest passage.<br />

Slate-streaked rocks from the byway<br />

pull open their pores. Quietly,<br />

I watch as carbon rolls out<br />

toward the surface.<br />

PERI<br />

A CARBON SEA SCENE<br />

POEM AND ART BY<br />

SOPHIA ZHAO<br />

Artist’s Statement<br />

I wanted to convey research’s brilliant<br />

ability to shift preconceived notions<br />

through my poem, “A Carbon Sea Scene,”<br />

which offers a window into the findings<br />

of Lidya Tarhan, Jiyuan Wang, and their<br />

colleagues recently published in Nature.<br />

Inspired by their stepwise discovery of an<br />

abiotic deep-sea carbon sink, I aimed to<br />

depict my own gradual understanding of<br />

their research by crafting a metaphoric<br />

“painting” representative of their study.<br />

To draw out the beauty of the authors’<br />

breakthrough, I relied on a poetic<br />

structure that “streche[d] down” the<br />

page—much like how the carbon cycle<br />

transcends depth—to emphasize the rich<br />

information that the deepest waters hold.<br />

Phrases such as “tousling the tides” and<br />

“seafloor, slumbering” maintain a steady<br />

rhythm that crescendos with “pull open<br />

their pores”—the most pivotal moment<br />

of this poem, and ultimately, the research<br />

of Tarhan, Wang, and their colleagues<br />

(Tracking Carbon’s Underwater Dive, pg.<br />

12-13). ■<br />

METER<br />

www.yalescientific.org<br />

May 2023 Yale Scientific Magazine 39


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