YSM Issue 94.2

Yale Scientific

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

MAY 2021

VOL. 94 NO. 2 • $6.99

16

A BREAKTHROUGH

THERAPY FOR DIABETES

2D SOLUTIONS FOR 3D

12

PROBLEMS

TRACKING DOWN LETHAL

14

MOSQUITOES

GENERATING

19

RANDOMNESS

THE RADIO STATION AT THE

22

END OF THE UNIVERSE

TABLE OF

VOL. 94 ISSUE NO. 2

COVER

16

A R T

I C L E

A Breakthrough Therapy for Diabetes

Alex Dong

There is no cure yet for type 1 diabetes, a disease that affects more than one million Americans. Hear

the story of a new FDA Breakthrough drug, Teplizumab, that could not only treat the symptoms of

type 1 diabetes, but also delay or prevent its onset.

12 2D Solutions for 3D Problems

Catherine Zheng

Yale researchers studied the electrical properties of different materials to solve challenges in the

design of electronic devices.

14 Tracking Down Lethal Mosquitoes

Elizabeth Wu

Climate changes is rapidly expanding the range of disease-carrying mosquitoes. Scientists at the

Yale School of Environment tackled the issue by using cutting-edge artificial intelligence techniques.

19 Generating Randomness

Alexa Jeanne Loste

Random numbers play an integral role in cybersecurity and scientific discovery. A Yale team

invented a new laser-based mechanism to generate randomness at ultrafast speeds.

22 The Radio Station at the End of the

Universe

Brianna Fernandez

Dark matter is one of the most elusive problems facing physicists today. But researchers at Yale’s

Wright Laboratory might have found a new method to detect it.

2 Yale Scientific Magazine May 2021 www.yalescientific.org

CONTENTS

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

4

6

25

34

Q&A

NEWS

FEATURES

SPECIALS

Why do fragments spin after a nuclear fission split? • Meili Gupta

Identifying Deafness Mutations in the Iranian Population • Kelly

Chen

Stem Cell Therapy for Spinal Cord Injuries • Jerry Ruvalcaba

A Curious Salmonella Protein • Christopher Ye

"Like Dissolves Like": Updating Theories on Miscibility • Veronica

Brooks

Nanoscale Nucleation • Krishna Dasari

Stereochemistry Selection • Shudipto Wahed

Magnetism in Small Plants • Rayyan Darji

Racial Disparities in COVID-19 Mortality • Bella Xiong

ASIA: Assessing Social Identities • Tejita Agarwal

Memories of the Brainless Slime Mold • Malia Kuo

Bridging the Quantum Gap • Yu Jun Shen

Beauty is in the Eye of the Beholder • Lauren Chong

Gynecology for Guys: Male Birth Control • Angelica Lorenzo

Migratory Strategies: Past, Present, and Future • Madison Houck

Undergraduate Profile: Phyllis Mugadza (BS/MPH '22) • Eamon Goucher

Alumni Profile: Dr. C. Brandon Ogbunu (PhD '10) • Anna Calame

Science in the Spotlight: Vivek Murthy's Together: The Healing Power of

Human Connection in a Sometimes Lonely World • Hannah Huang

Science in the Spotlight: The Nocturnists • Ann-Marie Abunyewa

Counterpoint: Not-So-Identical Twins • Eva Syth

Into the Newsroom: A Conversation with Carl Zimmer • Sophia Li

www.yalescientific.org

May 2021 Yale Scientific Magazine 3

&

WHY DO FRAGMENTS SPIN AFTER

A NUCLEAR FISSION SPLIT?

By Meili Gupta

In 1938, chemists Otto Hahn and Fritz Strassmann

bombarded a uranium nucleus with a neutron. To their

surprise, they discovered that barium and krypton were

produced. This division of heavy nuclei was termed “fission,”

and since its discovery it has deeply intrigued physicists.

For decades, physicists have puzzled over why the resulting

fragments spin after nuclear fission. A recent collaboration

between scientists from France, Germany, the UK, and other

European countries offers clear answers.

At the IJC Laboratory in Orsay, France, scientists used highresolution

spectroscopy to inspect the fission of 232 Th, 238 U,

and 252 Cf. They specifically used a method from the University

of Manchester to measure the average spin of the fission

fragments. They discovered that the fragment spin appeared to

depend only on the fragment mass, not the mass of the original

nucleus or the mass or charge of its partner fragment. Their

results deny hypotheses that the spin is generated before the

nucleus splits (pre-scission), as these hypotheses predict equal

magnitude spins for partner fragments. The large asymmetries

in the angular momentum between the spins of heavy and

light partner fragments support a post-scission hypothesis and

the idea that the fragments should be treated as independent

quantal—discrete—systems.

Beyond deepening a fundamental understanding of fission,

these findings have important applications for nuclear

energy, since fragment spins influence the heating effects of

reactor gamma rays. This research may help unlock the full

potential of nuclear fission. ■

Wilson, J.N., Thisse, D., Lebois, M. et al. Angular momentum

generation in nuclear fission. Nature 590, 566–570 (2021).

https://doi.org/10.1038/s41586-021-03304-w


The Editor-in-Chief Speaks

FACING OUR CHALLENGES

It has been a challenging semester. Our Yale community, like much of the

rest of the world, has collectively grappled with burnout, isolation, and an

ongoing pandemic. For many of us, a small ounce of hope came towards the

end of the semester: vaccines, developed in record speeds using cutting edge

biomedical advances in mRNA and viral vector technology. Science provides us

a lot—a fundamental understanding of ourselves and our universe, an outlet for

human exploration. But these past few months, I’ve been particularly struck by

how science helps us respond to the challenges we face.

In this issue, we see science’s capacity to pose new solutions to persisting

problems—technical challenges in the fields of organic synthesis (pg. 9),

quantum computing (pg. 27), and dark matter detection (pg. 22); social

challenges such as gender inequity in birth control (pg. 30). This innovation can

come from both seasoned professors and new researchers: in our undergraduate

profile, we speak to a Yale mechanical engineering major who designed a device

to help those who menstruate manage their pain (pg. 34).

We also see how research can help us identify what problems we ought to

focus on at all, from public health studies that quantify racial disparities in the

COVID-19 pandemic (pg. 11) to ecological investigations that reveal to us the

threat that climate change poses to bird migration (pg. 32).

But I am perhaps most moved by scientists themselves and their ability to

persevere in the face of challenges inherent to the process of innovation. In this

issue’s cover story (pg. 16), we highlight the development of a groundbreaking

new drug that may be able to prevent type 1 diabetes. The treatment is the result

of thirty years of labor by a Yale researcher, who carried his work from the

cellular level to a nationwide clinical trial, even when disappointing preliminary

results and a lack of funding threatened his pursuits.

Science, of course, is not the end-all, be-all savior to all of humanity’s problems.

With every scientific innovation, from COVID-19 vaccines to rapidly advancing

AI technologies, comes a host of questions about trust, bias, injustice, inequality,

and more that we as a society must confront. Our Scope blog continues to

interrogate these ethical dimensions. But for this issue of Yale Scientific, after

such a dark year, I’d like to commend science for helping us see a bit of light.

To the Yale Scientific team, thank you for contributing your time and energy

despite the incredibly difficult semester. And to our readers, thank you for

continuing to support us despite all that the past few months have undoubtedly

brought upon you. Here’s to perseverance, hope, and innovation.

About the Art

Isabella Li, Editor-in-Chief

In this issue’s cover, I explore a

breakthrough therapy for diabetes

by illustrating its molecular

mechanism. I hope that the bright,

spring-like colors welcome this

treatment as one that will better

patients’ lives.

Sophia Zhao, Cover Artist

MASTHEAD

May 2021 VOL. 94 NO. 2

EDITORIAL BOARD

Editor-in-Chief

Managing Editors

News Editor

Features Editor

Special Sections Editor

Articles Editor

Online Editors

Copy Editors

Scope Editors

Newsletter Editor

PRODUCTION & DESIGN

Production Manager

Layout Editors

Art Editor

Cover Artist

Photography Editor

BUSINESS

Publishers

Operations Manager

Advertising Manager

Subscriptions Manager

OUTREACH

Synapse Presidents

Synapse Vice Presidents

Synapse Outreach Coordinators

Synapse Events Coordinator

WEB

Web Manager

Web Developer

Web Publisher

Social Media Coordinator

Web Designer

SENIOR STAFF WRITERS

Britt Bistis

Anavi Uppal

STAFF

Ann-Marie Abunyewa

Tejita Agarwal

Veronica Brooks

Dilge Buksur

Anna Calame

Kelly Chen

Frances Cheung

Mehana Daftary

Rayyan Darji

Krishna Dasari

Ivy Fan

Ellie Gabriel

Raquel Sequeria

Alex Dong

Eamon Goucher

Sydney Hirsch

Madison Houck

Malia Kuo

Cecilia Lee

Angelica Lorenzo

Alexa Loste Jeanne

Katherine Moon

Gonna Nwakudu

Emilia Oliva

Dhruv Patel

Rosie Rothschild

Isabella Li

James Han

Hannah Ro

Jenny Tan

Cindy Kuang

Nithyashri Baskaran

Maria Fernanda Pacheco

Meili Gupta

Cathleen Liang

Alex Dong

Brianna Fernandez

Hannah Huang

Christina Hijiya

Tai Michaels

Beatriz Horta

Ishani Singh

AnMei Little

Catherine Zheng

Elaine Cheng

Sophia Zhao

Crystal Xu

Blake Bridge

Jared Gould

Brian Li

Sophia Zhuang

Lauren Chong

Alice Zhang

Sophia Li

Blake Bridge

Jared Gould

Athena Stenor

Anavi Uppal

Sophie Edelstein

Matt Tu

Brett Jennings

Eten Uket

Megan He

Siena Cizdziel

Rayyan Darji

Jerry Ruvalcaba

Noora Said

Sydney Scott

Yu Shen Jun

Anasthasia Shilov

Eva Syth

Van Anh Tran

Shudipto Wahed

Elizabeth Wu

Bella Xiong

Christopher Ye

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

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

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

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NEWS

Genetics / Biomedical Engineering

IDENTIFYING

DEAFNESS

MUTATIONS IN

THE IRANIAN

POPULATION

BY KELLY CHEN

Hearing loss is a commonly overlooked sensory

disorder, even though it occurs all over the world.

One type of deafness is autosomal recessive

nonsyndromic deafness (ARNSD), a comparatively prevalent

type of deafness in Iran. Working with researchers from

Shiraz University of Medical Sciences, Emily Smith and Arya

Mani from Yale University used DNA sequencing techniques

to identify mutations that cause ARNSD.

The research established that causative mutations were

found in all ten Iranian families studied. Mutations were found

primarily within GJB2 genes, which code for gap junction

beta proteins. Novel mutations in the Iranian population were

found also within the TMC1, ESRRB and MYO15A genes.

These genes encode proteins involved in hearing. “These

mutations often impair the function of cochlear hair cells,”

Mani said. “For instance, TMC1[transmembrane channel

like] is a pore-forming component of mechanosensory

transduction channels in auditory and vestibular hair cells

with important function in hearing.”

Identification of common mutations allows for early

diagnosis of ARNSD. Earlier diagnosis, in turn, leads to

proactive treatment plans, such as cochlear implants or

speech therapy. “There are ongoing discussions in the media

about people [who are] affected by deafness but are afraid of

seeking help…[or] they try to deny their illness, so they are

not as stigmatized. But once they are treated or wear their

hearing aid, they catch up with challenges, and suddenly

they see the world changes for them,” Mani said. ■

Dianatpour, M., Smith, E., Hashemi, S., Farazifard, M.,

Nezafat, N., Razban, V., & Mani, A. (2021). Identification

of homozygous mutations for hearing loss. Gene, 778,

145464. doi:10.1016/j.gene.2021.145464

STEM CELL

THERAPY FOR

SPINAL CORD

INJURIES

BY JERRY RUVALCABA

IMAGE

COURTESY

OF PIXABAY

Spinal cord injury treatment without surgery—the work

of science fiction or a soon reality? Spinal cord injuries

continue to be a challenging medical issue: they commonly

cause disability yet have limited viable treatments. Discovering

such remedies has been one of the drivers behind the longstanding

relationship between researchers at the Sapporo

Medical University of Japan and the Yale School of Medicine.

Building on their focus on pre-clinical work with stem cells, this

collaboration has led to the implementation of a clinical trial

utilizing intravenous injection of stem cells.

In the study, patients’ stem cells were isolated from their bone

marrow and grown using their serum. “It’s a completely closed

system… it’s personalized medicine,” said Jeffery D. Kocsis,

professor of neurology and neuroscience at Yale. Following

the cells’ injection, the researchers monitored the patients and

reported neurologic improvements in twelve of the thirteen

patients under the ASIA Impairment Scale for sensory and motor

levels. Researchers did not detect adverse effects after injection.

“The studies are, I think, quite exciting and give us great hope

that we can push on with this,” Kocsis said.

While these results are promising, Kocsis notes that they

are only anecdotal. “The study that was done in Japan was not

blinded; it was observational and the paper [described the tests]

as case studies,” he said. With this, Kocsis is cautious to declare

the results conclusive and is looking forward to a future, blinded

study performed in New Haven for more definitive answers. ■

Honmou, O., Yamashita, T., Morita, T., Oshigiri, T., Hirota, R., Iyama,

S., Kato, J., Sasaki, Y., Ishiai, S., Ito, Y. M., Namioka, A., Namioka,

T., Nakazaki, M., Kataoka-Sasaki, Y., Onodera, R., Oka, S., Sasaki,

M., Waxman, S. G., & Kocsis, J. D. (2021). Intravenous infusion

of auto serum-expanded autologous mesenchymal stem cells

in spinal cord injury patients: 13 case series. Clinical Neurology

and Neurosurgery, 203, 106565. https://doi.org/10.1016/j.

clineuro.2021.106565


Microbiology / Chemistry

NEWS

A CURIOUS

SALMONELLA

PROTEIN

SOPD’S STIMULATION AND INHIBITION OF

INFLAMMATION

BY CHRISTOPHER YE

IMAGE COURTESY OF NIAID

The bacterial pathogen Salmonella typhimurium causes

intestinal inflammation. S. typhimurium injects effector

proteins such as SopD that stimulate a signaling cascade,

ultimately leading to inflammation. However, researchers from Yale

and Shandong University discovered that SopD is bifunctional and

can alternatively stimulate or inhibit inflammation. “It contains the

‘Yin and Yang’ elements of the Salmonella/host interaction within

the same protein… a remarkable piece of evolution,” said Jorge

Galán, lead researcher of the study and chair of the Department of

Microbial Pathogenesis at Yale School of Medicine.

“[Inflammation is] essential for [S. typhimurium] to colonize

the intestinal tract, since it allows Salmonella to [compete] with

the resident microbiota and secure nutrients that are otherwise

not accessible in the uninflamed intestine,” Galán said. Rab8

is a regulatory protein that is central for an anti-inflammatory

signaling pathway that helps the host recover homeostasis after

inflammation. Therefore, by inhibiting Rab8, SopD stimulates

inflammation and helps the pathogen replicate within the intestine.

When the researchers solved the SopD-Rab8 complex’s crystal

structure, they identified SopD’s unexpected second function: SopD

can activate Rab8 and stimulate an anti-inflammatory response. In

other words, opposing enzymatic activities are present within the

same protein. Rab8 normally binds to GDI2, an inhibitor that blocks

Rab8 activity. However, SopD can displace GDI2 to activate Rab8 and

inhibit inflammation. By doing so, S. typhimurium sacrifices virulence

to preserve host stability, maximizing its ability to continue replicating.

“[This research is] providing major insight into the pathogenesis

of chronic intestinal inflammatory diseases such as Crohn’s disease,”

Galán said. Understanding Salmonella has implications in the

development of novel therapeutic strategies. ■

Lian, H., Jiang, K., Tong, M. et al. The Salmonella effector protein

SopD targets Rab8 to positively and negatively modulate the

inflammatory response. Nat Microbiol (2021). https://doi.

org/10.1038/s41564-021-00866-3


“LIKE-DISSOLVES-

LIKE”

UPDATING THEORIES ON

MISCIBILITY

BY VERONICA BROOKS

IMAGE COURTESY OF WIKIMEDIA COMMONS

Miscibility, or the ability for liquids to mix, is often

determined by the “like-dissolves-like” rule, which is

largely qualitative. It remains difficult to quantitatively

determine how “alike” two substances are. But by using the

dielectric constant, Bilin Zhuang, an assistant professor at Yale-

NUS, developed a model that accurately predicts the miscibility

of two liquids using their permanent dipole moments, which

arise from differences in electronegativity across a molecule.

The dielectric constant is a number assigned to a substance

based on how polarized it becomes in an electric field. A molecule

with a high dielectric constant has higher polarity and a greater

ability to stabilize charges in an electric field. Materials with

similar dielectric constants often mix well. Zhuang’s model also

uses the free energy of mixing to predict miscibility of two liquids.

This model accurately fits experimental data when compared to

previous theories that use a similar number of parameters.

However, these new equations are unable to account for

hydrogen bonding, which leads certain liquids to adopt

conformations that the dielectric constant does not predict.

Zhuang’s next steps will focus on developing miscibility

predictors for hydrogen bonding liquids and polarizable

liquids, substances with no permanent dipoles.

Ultimately, these new equations will be particularly

useful for predicting the miscibility of newly synthesized

molecules. It also saves time at the bench when one studies

multi-component mixtures. “We can just plug in the number

and roughly see what the dielectric constant is [and] its

miscibility,” Zhuang said. ■

Zhuang, B., Ramanauskaite, G., Koa, Z. Y., & Wang, Z.-G. (2021).

Like dissolves like: A first-principles theory for predicting liquid

miscibility and mixture dielectric constant. Science Advances,

7(7), 1–7. https://doi.org/10.1126/sciadv.abe7275


NEWS

Chemistry

NANOSCALE

NUCLEATION

Insight into the unusual

mechanism of contact

freezing

BY KRISHNA DASARI

IMAGE COURTESY OF FLICKR

Freezing: a simple phase transition with a surprisingly complex With these advancements, the researchers were able to

set of mechanisms. Researchers use freezing dynamics to study simulate the nanoscale dynamics of contact freezing for two

the crystallization of various materials, but not all kinds of mW-based liquids, one that had a surface freezing propensity

freezing are mechanistically understood. Graduate student Sarwar

Hussain and professor Amir Haji-Akbari in the Department of

Chemical and Environmental Engineering at Yale recently simulated

contact freezing to unravel its unique mechanism.

In contact freezing, a water droplet that is supercooled—below

freezing temperature but still liquid—collides with an external

particle that promotes nucleation, the initiating step in the process

of freezing. This results in unusually rapid ice formation. However,

why exactly freezing proceeds so quickly remains unclear. Previous

studies have suggested two key points. First, the rate of contact

freezing is related to the liquid’s tendency to surface freeze—that

is, to rapidly freeze its surface relative to the interior. Second, the

nucleating particle doesn’t necessarily have to directly disrupt the

liquid-vapor interface to increase the freezing (nucleation) rate.

The researchers’ results ruled out the prevailing theories on freezing

mechanism. “[These findings] were not necessarily explained by the

previous mechanisms which said that there has to be some sort of

mechanical disturbance in the free interface between the liquid and

the vapor for the increased freezing rate to take place,” Hussain said.

Further experiments into this nucleation mechanism are

hindered by the limits of technology. Freezing events occur on

the nanosecond timescale and create ice nuclei containing only

hundreds to thousands of molecules. They cannot be observed

with sufficient resolution, so the mystery of high nucleation rates

during contact freezing is difficult to approach experimentally.

What can’t yet be accomplished in a physical lab, though,

can now be done computationally. Two major advancements

allowed for the accurate simulation of contact freezing. The first

was the mW model, a water-like tetrahedral model liquid that

enables rapid simulation while still considering interactions

like hydrogen bonding. The second was the development of

jumpy forward flux sampling, a novel sampling technique

conceptualized by Haji-Akbari to address the shortcomings

of the original forward flux sampling method. The original

and one that did not. By simulating supported nanofilms of

the liquids, they were able to exclusively investigate the effect

of the proximity of the nucleating particle to the vapor-liquid

interface on the nucleation rate.

From their simulations, they observed that only the surface

freezing liquid’s nucleation rate was affected by proximity

to the nucleating particle, increasing the nucleation rate by

orders of magnitude. Moreover, they discovered that in such a

case, freezing proceeds through the formation of hourglassshaped

nuclei, a unique property that mechanistically explains

the increased nucleation rate. Compared to the spherical capshaped

nuclei of classical models, hourglass-shaped nuclei have a

smaller surface area exposed to the liquid. According to classical

nucleation theory, the smaller liquid-exposed surface area lowers

the nucleation barrier, allowing nucleation to proceed faster.

Their findings have implications for understanding contact

freezing of water in the atmosphere, a phenomenon important

for predicting weather patterns. These results support the

theory that water may be capable of surface freezing, giving it

access to rapid nucleation through contact freezing. However,

the authors also note that other agents in the atmosphere

may also contribute to nucleation rate, making it difficult to

conclude that the proximity effect of surface freezing liquids is

necessarily the main cause for atmospheric nucleation rates.

More broadly, their discovery of this non-classical nucleation

mechanism provides a roadmap to study other non-classical

processes. For example, scientists may investigate nucleation in

the vicinity of surfaces with different ice-forming properties,

such as a protein with hydrophilic and hydrophobic patches.

“The question is, if you put that protein inside supercooled

water, what will happen? How will the critical nucleus look like,

and how will the rate be sensitive to temperature, for example?

These are all questions that our work gives a good conceptual

framework to pursue,” Haji-Akbari said. ■

method could be used to estimate the likelihood of freezing

events progressing toward complete freezing, but Haji-Akbari’s

Hussain, S., & Haji-Akbari, A. (2021). Role of Nanoscale

version accounts for the jumpiness of freezing progression Interfacial Proximity in Contact Freezing in Water. Journal of

caused by the coagulation of ice particles. “If you do not take the American Chemical Society, 143(5), 2272–2284. https://

into account these jumps, you can underestimate the nucleation doi.org/10.1021/jacs.0c10663

rate by several orders of magnitude,” Haji-Akbari said.


Chemical Engineering

STEREOCHEMISTRY

SELECTION

The catalytic synthesis of

stereopure oligonucleotides

NEWS

IMAGE COURTESY OF PIXABAY

Nucleotides, the building blocks of DNA and RNA, can

be synthetically designed to mimic their biological

counterparts and interact with the cellular environment.

An important class of nucleotide molecules are cyclic dinucleotides

(CDNs), two single nucleotides that bind to form a ring. For example,

cGAMP is a naturally occurring CDN that can drive immune

response by activating the stimulator of interferon genes (STING)

protein. Because interferon genes are critically involved in immune

cell signaling, STING pathways are being extensively evaluated in

cancer immunotherapies, and CDNs such as cGAMP may serve as

promising new drugs. Synthetically manufacturing them represents

an important step in bringing these drugs to mass market.

A powerful method of increasing metabolic stability and therapeutic

potential of CDNs is to modify their native phosphodiester linkages into

phosphorothioate (PS) double-bonds. However, doing so introduces

an additional layer of complexity by rendering the central phosphorus

(P) atoms stereogenic (chiral), meaning different spatial orientations—

stereoisomers—of the same connected groups are possible. An analogy

for stereoisomers is a pair of baseball gloves in which one is left-handed

and the other is right-handed—although otherwise indistinguishable,

the right-handed glove will not fit on a left hand, and vice versa.

Each CDN stereoisomer, despite possessing identical atomic

connectivities, displays markedly different physical properties and

biological activities. The importance of stereochemistry is best

highlighted by the infamous case of thalidomide, a drug developed

in the 1950s that was marketed to treat morning sickness in pregnant

women. One of its stereoisomers has sedative effects, whereas the

other caused birth defects. As a result, thousands of children whose

mothers took thalidomide during pregnancy had severe birth

defects, since both stereoisomers were present in the medicine.

Most synthetic methods for preparing PS-derived CDNs are

nonselective in stereochemical outcome, relying on intensive purification

techniques or large quantities of auxiliary reagents to produce stereopure

products. In a recent study published in Science, the Scott Miller lab

at Yale’s Department of Chemistry, in collaboration with Takeda

Pharmaceutical Company, reported the first catalytic, stereocontrolled

synthesis of dinucleotides. Lead author Aaron Featherston, along with

a team of academic and industrial researchers, sought to address the

aforementioned problem using asymmetric catalysis. Catalysts, which are

regenerated throughout the course of a reaction, could ideally be used in

small amounts to facilitate the stereoselective assembly of PS compounds.

The first step of oligonucleotide synthesis is often achieved using

excess amounts of an acid activator. Symmetric chiral phosphoric acids


BY SHUDIPTO N. WAHED

(CPAs) have proven to be powerful catalysts in several asymmetric

transformations that isolate one stereoisomer. Recently, the Miller lab

developed an additional class of CPAs containing a modified amino

acid, phosphothreonine (pThr). Their rationale was that the amino acid,

a building block of proteins, could conceivably help impart selectivity on

par with enzymes, the ultra-specific protein catalysts of nature.

Accordingly, Featherston and the team assessed the ability of

these two classes of CPAs to asymmetrically couple two select

nucleotides, guanosine and adenosine. They found that several

pThr-derived catalysts greatly biased coupling towards one product

stereoisomer. Alternatively, the symmetric CPA catalysts were

highly selective for the other stereoisomer. The researchers thus

demonstrated two distinct, complementary catalyst frameworks,

allowing for the synthesis of either stereopure isomer.

The researchers then evaluated the ability of these catalysts

to asymmetrically couple a broader range of representative

nucleotides, finding that their stereoselective catalyses could

be applied to other base pairs beyond the guanosine-adenosine

coupling initially tested. Although selectivity decreased for

certain nucleotide couplings, the chemists demonstrated that their

approach is generalizable and can potentially yield a universal

catalyst. Finally, the group applied their method to the synthesis of

PS-modified cGAMP, showing that the pThr and symmetric CPA

catalysts could allow for an efficient, stereocontrolled preparation.

The researchers found, for the first time, a stereocontrolled

synthesis of dinucleotides using two catalyst frameworks.

Oligonucleotide syntheses have long struggled with controlling

P-stereogenicity, which reduces the efficacy of nucleotide-based

therapeutics. This new approach both provides efficient access to a

dinucleotide P-stereoisomer and enables preparation of stereopure

analogs of cGAMP, a CDN of great biological significance.

In the future, the Miller lab may dive deeper into the catalysts’

mechanism of action. A longer-term ambition would be to develop a

more universal catalyst framework that can facilitate the asymmetric

synthesis of all possible nucleotide couplings. Their current findings

will prove vital to the field of oligonucleotide chemistry, as synthetically

modified nucleotides continue to grow in importance. “It was a great

collaboration, and I think we were able to make a significant impact by

developing some really cool chemistry,” Featherston said. ■

Featherston, A. L., Kwon, Y., Pompeo, M. M., Engl, O. D., Leahy, D. K.,

& Miller, S. J. (2021). Catalytic asymmetric and stereodivergent

oligonucleotide synthesis. Science, 371(6530), 702–707.


NEWS

Astrophysics

MAGNETISM

IN SMALL

PLANETS

BY RAYYAN DARJI


Within the expansive solar system, there are bodies of

numerous types and sizes, and our understanding

of them is far from complete. A key tool toward

furthering our understanding of our own planet Earth and

other bodies in the solar system is the study of magnetic fields.

In general, the magnetization of a body in space can tell us

about how it formed, what it is made of, and how it has cooled

and evolved over time.

Larger bodies like planets are believed to have been formed

from the collisions and eventual conglomeration of smaller

bodies called planetesimals. By studying planetesimals,

scientists can apply those findings to larger planets, which

are far more difficult to directly study. Building upon existing

models, researchers from Yale’s Department of Earth and

Planetary Sciences developed a new model to understand

magnetism in planetesimals.

Evidence that planetesimals are magnetized comes from the

analysis of meteorites, which are fragments of planetesimals

that have made it to the Earth’s surface. Magnetization of

planetesimals implies they were already segregated like miniplanets

into a metallic core (in which the magnetic field is

generated) and rocky mantle and crust, even before they

accreted to make bigger planets.

Certain conditions must be present for a body to be able

to generate a magnetic field. “To get a magnetized body, you

need an electrically conductive fluid—like molten iron in

the core—and the fluid needs to be moving at a fast enough

rate to generate a magnetic field,” said Elvira Mulyukova, a

co-author of the paper published in Physics of the Earth and

Planetary Interiors. This motion is referred to as dynamo

activity. “There also needs to be a solidifying, cooling crust

at the surface that can record that induced magnetic field,”

Mulyukova said.

The top of metallic cores in planets and planetesimals will

crystallize over time to a solid material, making that region

heavier and causing it to sink downward—a process known as

delamination. When the solid material drops off, it tends to do

so in big blobs, and when these blobs disconnect, they form

geological intrusions known as diapirs. That delamination

can cause the fluid in the core to stir fast enough to generate

dynamo activity and ultimately a magnetic field.

In deducing how magnetization occurs in small planetesimal

cores, a primary obstacle is the inability of the smaller bodies

to sustain sufficient dynamo activity. “When the solid outer

shell delaminates, the falling of those solid bodies is so fast

and sporadic that it would require a lot of them to be falling

at the same time to induce vigorous motion of the fluid and

thus generate a dynamo; moreover, they need to be falling over

a long period of time for the induced magnetic field to get

recorded,” Mulyukova said.

Instead, by analyzing various factors influencing dynamo

activity, the researchers proposed the nature of planetesimal

cores may be the cause of their magnetism. Because

planetesimal cores are not pure iron, the diapirs formed are

probably porous, like iron snowballs. “For a sinking porous

diapir, the motion of the liquid in the surroundings and the

motion of the liquid through the pores will generate enough

velocity of the liquid to induce a magnetic field,” said David

Bercovici, the another co-author of the paper.

More research must be done to fully understand magnetism

in planetesimals and how it relates to larger planets. “The

presence of magnetization in an object tells us something

about its differentiation history and composition, which

in turn allows us to understand the types of planetesimals

that likely have created our own planet,” Mulyukova said.

Although bound by certain limitations and assumptions, the

theoretical model produced from this study paves the way for

promising future research, including developing a model for

multiple diapirs, and ultimately understanding the magnetic

and thermal histories of planetesimals—the building blocks

of our planet. ■

Bercovici, D., & Mulyukova, E. (2021) Magnetization of

sinking porous diapirs in planetesimal cores. Physics of

the Earth and Planetary Interiors, 313, 106678. https://

doi.org/10.1016/j.pepi.2021.106678


Public Health

NEWS

RACIAL

DISPARITIES

IN COVID-19

MORTALITY

BY BELLA XIONG

IMAGE COURTESY OF GETTY IMAGES

It has been frequently reported that racial disparities persist

in COVID-19 mortality rates, but how large are these

disparities, and what factors create them? Exactly one

year after the World Health Organization (WHO) declared

COVID-19 a pandemic, a team of researchers from the Yale

School of Public Health, led by graduate student Alyssa Parpia,

published a study evaluating how the pandemic has reflected

systemic racism in the United States. The study looked at the

disproportionate burden borne by Black Michiganians in the

COVID-19 pandemic relative to their White counterparts.

Specifically, the team studied mortality attributable to

COVID-19. While only 14.1 percent of the Michigan population is

Black, Black Michiganians experienced about thirty-five percent

of COVID-19 deaths in the entire state as of November 2020.

The researchers compared the demographic characteristics—

such as age, sex, and total number of comorbidities (presence of

more than one illness or disease in one patient)—of White and

Black individuals. Even after accounting for these factors, Black

individuals were still at higher risk of COVID-19 mortality than

their White counterparts, indicating that race is a driving factor

behind the disproportionate mortality burden in Michigan.

These results shine a light on systemic racism in the United

States. The team’s research demonstrated that chronic conditions

alone are not responsible for the increased mortality rate among

Black individuals, especially for those who are younger. Systemic

racism, for one, has created racial disparities in socioeconomic

status. And even when socioeconomic status is not a factor,

biases and stereotypes have a serious impact on how doctors

treat people of color, especially Black individuals. For example,

a study conducted by the National Institutes of Health reported

that between 2005 and 2016, the admission rate into hospitals was

ten percent lower for Black individuals compared to their White

counterparts. This can lead to misdiagnosis of illnesses, a lack of

proper pain management, and increased health risks in general.

Histories of systemic racism have created a lack of trust between

medical personnel and racialized populations.

Parpia’s study helps us quantitatively identify racial disparities

in the United States, a crucial step toward addressing systemic

racism. Stopping the pandemic will not stop the inequalities built


by hundreds of years of racially discriminatory and oppressive

policies. Parpia noted that there are many other important factors

linked with systemic racism that we should continue to explore.

Racial inequality in employment presents one such example. As

“essential workers,” grocery store or transit employees—positions

disproportionately held by Black Americans—have less access to

personal protective equipment compared to hospital employees.

Many who do not have access to higher paid positions are also

excluded from health insurance. In addition, essential workers

might not have access to paid sick leave and are less likely to socially

distance because of the nature of their jobs.

Race-based socioeconomic inequities and inaccessibility of

healthcare have heightened chances of COVID-19 exposure and

lowered overall survival rate. “The pandemic magnified many existing

issues we had in the U.S., and we should use it as an impetus to change

our entire healthcare structure,” Parpia said. Even as the spread of the

COVID-19 dies down, it is imperative to examine underlying reasons

why certain populations are more at risk of contracting and dying

from COVID-19 than others. These communities will continue to be

more at risk if we maintain the status quo.

Parpia suggested solutions such as providing paid sick leaves, living

wages, and universal healthcare, as well as restructuring the U.S.

prison system. These supports would help ensure that people are able

to adhere to the stay-at-home guidelines put in place to control disease

transmission. This, in turn, could have compounding effects. For

example, providing paid sick leaves would allow for people to avoid

exposure to others when sick, thus decreasing the spread of the virus.

“These should be seen as basic rights, and for some reason,

they are not,” Parpia said. And while the proposed solutions

center on just one aspect of systemic racism, according to

Parpia, they “will have wide-reaching implications on the ability

of racialized populations to be able to approach a semblance of

equity with White populations in the United States.” ■

Parpia, A. S., Martinez, I., El-Sayed, A. M., Wells, C. R., Myers,

L., Duncan, J., ... & Pandey, A. (2021). Racial disparities

in COVID-19 mortality across Michigan, United States.

EClinicalMedicine, 33, 100761.


FOCUS

Material Science

3D

2D SOLUTIONS

TO

PROBLEMS

Studying the electrical properties of

altered 2D materials

BY CATHERINE ZHENG

Electronics are ubiquitous in our

everyday lives—they are in the cars

we drive, the microwaves that heat

up our food, and the computers we use.

This omnipresence is due to technology’s

constant evolution. Currently, unbelievably

complex technologies can be found in even

common devices, such as our cell phones.

The creation of materials that are elaborate

in their complexity but simple in their

design—and can thus be implemented

into many technological devices—sits at

the intersection of electrical engineering

and materials science.

Judy Cha, Yale Professor of Mechanical

Engineering and Materials Science, has

led her lab in important work within these

fields. Her team focuses on discovering

new layered materials that can be used

in electronics. Through manipulating

their electrical properties, they seek to

understand more about the materials

themselves and how they can be used. The

team hopes to elucidate which materials

might be particularly ideal for a certain

electronic device, as well as how the

materials’ performance can be improved by

altering electrical properties.

In the beginning of 2021, Cha’s group and

its collaborators published two studies: one

focusing on the mechanical properties of

graphene with lithium between its layers,

and the other on molecular doping—the

addition of small molecules to materials to

activate them for use in electronics.

ART BY SOPHIA ZHAO

Lithium-Ion Batteries

2D materials are usually approximately one

to three atoms thick. They come from layered

materials that are exfoliated down to a single

layer. The properties of 2D materials normally

change when their layers are isolated.

Graphite, commonly found in pencil lead,

is a classic example of this: graphite consists

of layers of graphene, and the individual

graphene layers have properties that differ

substantially from those of graphite as a

whole. To harness such materials for device

applications, it is important to understand

these thickness-dependent changes.

Lithium intercalation into graphite—or,

the insertion of lithium between layers

of graphene that are held together by

van der Waals (vdW) forces—is essential

to create lithium-ion batteries, which

power many of our modern electronics.

Staging, or structural ordering, minimizes

electrostatic repulsions within graphite’s

crystal lattice, allowing lithium to order

itself between the van der Waals gaps of

graphene. Initially, lithium is randomly

distributed throughout the graphite, but as

the lithium concentration increases, there’s

a phase transition where lithium moves

laterally to form intercalated regions that

are vertically separated by unintercalated

regions. The kinetics of lithium moving

between the sheets of graphene are directly

related to how well the battery performs.

This staging process is well understood

for bulk graphite, which is thick. But on a

nanoscale, the way lithium and graphene are

confined so closely together affects the overall

structure. As lithium makes its way between

vdW gaps, these gaps expand to accommodate

the new atoms. However, anchoring graphene

sheets by clamping the edges down changes

the way lithium interacts with the graphene.

This constrains how much the graphene is able

to open, and it requires more work for lithium

to squeeze into those gaps. The kinetics of

lithium diffusion are also slowed down, since

it becomes more difficult for lithium to move

between the graphene sheets.

The effect of this mechanical strain sparked

the interest of Cha’s group. To investigate it

further, they used thin sheets of graphene—

between four and fifteen layers thick—with

gold electrodes on top that acted as a clamp.

Although these electrodes were only onehundred

nanometers thick, each layer of

graphene was even thinner: one-third of a

nanometer. The difference in size allowed the

gold to act as a source of pressure and hold

down the ends of the graphene sheets.

But as they observed this configuration,

the group realized that, while the edges of

the graphene sheets stayed still, the center

would expand freely, stretching in both the

x and y directions and causing strain in the

graphene. “Interestingly, what we found is

this strain can delay the lithiation kinetics

of graphene,” said Josh Pondick, a PhD

candidate in Cha’s lab and one of the lead

researchers for this experiment—lithiation

12 Yale Scientific Magazine May 2021


Material Science

FOCUS

referring to the process by which a lithium

ion replaces hydrogen atoms.

The team looked at these properties

in different thicknesses of graphene

with in situ Raman spectroscopy, a

method that provides molecularlevel

information about material

surface structures based on light

scattering. They found that,

as the thickness of graphene

increases, staging is delayed,

requiring more electrochemical

voltage to be induced.

A major obstacle in this study

arose while dealing with lithium,

since it is a rather flammable

chemical. Lithium-ion batteries are

typically assembled in glove boxes filled

with an inert, unreactive gas. However,

to experimentally monitor things like

electrical properties, the lithium had to be

taken out of the glovebox. “We spent quite a bit

of time trying to devise device geometry and

architecture that would allow us to contain all

of these volatile chemicals inside a small pouch

while we could still safely take it out and do the

types of measurements that we wanted to do,”

Cha said. But even with these tricky chemical

properties under control, simply handling

these materials was a challenge due to their

small size. The flakes of graphene are on the

order of ten to thirty microns—about the reallife

size of a white blood cell. Thus, techniques

in lithography, a special form of printing, were

required to add the gold electrodes.

With the push for new kinds of batteries

that use metals like magnesium and sodium

rather than lithium, there are plans to see

the results of these different kinds of atoms

being intercalated in graphene. These atoms

are bigger and will undoubtedly provide a

larger mechanical strain. Given how strong

graphene is, researchers are also considering

looking into new materials—notably

heterostructures that consist of multiple

layers of different 2D materials. Adding

intercalants could allow scientists to tune

the electrical and chemical properties of

these structures to be used in many different

devices, from optoelectronic to logic devices.

Molecular Doping

Alongside the research on lithium-ion

batteries and graphene, Cha’s group also

published a study on molecular doping.

An example of molecular doping is

adding boron or phosphorus to silicon,

which activates silicon so that it can be

used in electronics. This is particularly

Professor Judy Cha attempts to measure a device on the probe station.

useful for transistors, which are an

important component of computers.

Adding impurity atoms to a 2D material

like molybdenum sulfide (MoS 2

) is not as

simple as doing so to a single layer of inactive

atoms. The method used in this study involved

sprinkling molecules on top of the 2D material.

The molecules readily gave electrons to the

material, slightly altering its properties. For this

particular study, a synthetic organic molecule

known as DMAP-OED was added to MoS 2

.

To evaluate the effect of this compound on the

2D material, the number of electrons donated

from it to the material was investigated.

Finding the proper technique to do this

proved to be an arduous process. Given

the small size of the molecules, optical

microscopes would be useless. Although

electron microscopes have higher resolution,

they would also be ineffective, since they

would burn through all the molecules.

Alternative spectroscopy techniques were

also considered, but they were too crude to

ABOUT THE AUTHOR

PHOTO COURTESY OF LAUREN CHONG

properly count the number of molecules.

In the end, Cha’s group landed on atomic

force microscopy. This method, which uses

a sharp tip to scan a surface by interacting

with it and tracing its topography, allows for

high resolution of small objects.

Ultimately, Cha’s group found that

DMAP-OED donates 0.63 to 1.26

electrons per molecule to MoS 2

—record

molecular doping levels.

This work represents one of the first

experiments of such a nature done with an

organic electron donor. Thus, it will likely lead

to the development of more organic electron

donors beyond DMAP-OED for this purpose.

Moving ahead, Nilay Hizari, Yale Professor of

Chemistry and the collaborator involved in

the making of DMAP-OED, looks forward to

better understanding molecular doping levels

in the context of other molecules and materials.

“Now, there’s a whole range of small molecules

we could try on [those] 2D materials to get

some kind of desired property,” he said. ■

CATHERINE ZHENG

CATHERINE ZHENG is a sophomore BME major in Pauli Murray College. In addition to writing for YSM,

she’s involved in research and other organizations on campus like WGiCS.

THE AUTHOR WOULD LIKE TO THANK Professors Judy Cha, Nilay Hizari, and Josh Pondick for their

time and enthusiasm in sharing their research.

FURTHER READING

Pondick, J. V., Yazdani, S., Yarali, M., Reed, S. N., Hynek, D. J., & Cha, J. J. (2021). The Effect of Mechanical

Strain on Lithium Staging in Graphene. Advanced Electronic Materials, 7(3), 2000981. doi:10.1002/

aelm.202000981

Yarali, M., Zhong, Y., Reed, S. N., Wang, J., Ulman, K. A., Charboneau, D. J., . . . Cha, J. J. (2020). Near‐

Unity Molecular Doping Efficiency in Monolayer MoS 2. Advanced Electronic Materials, 7(2), 2000873.

doi:10.1002/aelm.202000873



FOCUS

Ecology

TRACKING DOWN

LETHAL MOSQUITOES

Machine learning to map the

genetic connectivity of A. aegypti

in the southern United States

BY ELIZABETH WU

With global temperatures

reaching record highs over the

last few years, climate change

has expanded the ranges of diseasecarrying

animals. Even tiny insects,

such as Aedes aegypti mosquitoes, which

are native to Africa, are not exempt

from this trend. Because of their highly

invasive nature, recent increases in global

temperatures have allowed the range of A.

aegypti to continue expanding worldwide,

throughout tropical and temperate

regions. In the United States, they can be

found in the southern states, most notably

in Texas, Florida, and California. They

prefer warm, humid areas close to humans

who can serve as sources of bloodmeals for

female mosquitoes. Feasting on our blood

provides not only a means for A. aegypti to

nourish themselves, but also allows them

to transmit infectious diseases like yellow

fever, Zika, dengue, and chikungunya.

Current climate trends could result in

the exposure of one billion additional

people to these diseases. The fact that, with

the exception of yellow fever, there are

no reliable and widely used vaccines for

these diseases creates an urgent need for

improved tracking and management of A.

aegypti populations. Two scientists at the

Yale School of the Environment—Evlyn

Pless, a postdoctoral researcher at UC Davis

who completed her graduate studies in

ecology and evolutionary biology at Yale,

and Giuseppe Amatulli, a research scientist

in geocomputation and spatial science—

collaborated on a recent study to tackle this

pressing environmental issue. Their goal

was to map North American landscape

connectivity for A. aegyti mosquitoes.

Old Limitations in Landscape Genetics

Landscape genetics, which is the study of

organisms’ population genetic data alongside

landscape data from their habitats, provides

scientists with helpful information that could

be used to control invasive species, such as

A. aegypti. Classical models of population

genetics relate increased genetic differentiation

to increased geographical distance, but these

models do not account for environmental

limitations on dispersal, such as geographic

barriers, or for landscape variables that

facilitate connectivity, like favorable climate.

A common approach to incorporate

environmental data into a model of genetic

connectivity is “resistance surface mapping.”

In this technique, a map of pixels is created

where each pixel represents the hypothesized

resistance of an organism’s movement.

These hypotheses consider environmental

variables. But although the resulting map of

resistance surfaces allows for extrapolation

of genetic distributions across the region,

this method involves substantial subjectivity,

as it relies on the hypothesized effect of an

environmental factor on population mobility.

Prior studies attempted to circumvent the

subjectivity of resistance surface mapping

by modelling genetic connectivity directly

from environmental data and iteratively

refining the model using least cost path

analysis, a mathematical technique that

estimates the least resource-intensive route

along which an organism could travel.

However, according to Amatulli and Pless,

this model was limited because it employed a

mathematical method known as maximum

likelihood estimation, which establishes

a relationship between environmental

variables and genetic distances before the

model is built. The model produced by

this methodology can therefore “overfit”

the data: while it may have been optimized

to match the data, it does not necessarily

make accurate ecological estimations.



Ecology

FOCUS

A New Approach to Modeling

To improve upon these previous models,

Pless and Amatulli took a groundbreaking

approach towards determining the

relationship between landscape variables

and genetic distance. First, they sampled

mosquitos from thirty-eight sites across

North America and calculated the genetic

differences between mosquitoes in each of

those sites. Open-source data for twenty-nine

different environmental factors, such as daily

temperature ranges and accessibility to major

cities, served as variables meant to explain

and predict genetic distances. For every pair

of sites in the set of thirty-eight sampling

sites, the researchers calculated average

values describing each of the twenty-nine

environmental factors that lay in between.

Using those values on genetic distances and

environmental factors, Pless and Amatulli

employed a fascinating strategy to predict

the effects of landscape conditions on genetic

connectivity: they used a machine learning

method called a random forest (RF)—a

predictive model based on aggregations of

possible effects of different factors—to create

landscape resistance maps. In doing so, they

generated a map representing landscape

resistance, which measured the difficulty

of mosquito migration at any particular

point based on all of the twenty-nine

environmental factors combined.

Using the resistance map built by RF, least

cost paths were drawn between each pair

of thirty-eight sampling sites. These paths

describe the least energetically expensive

routes between sites that could be taken

by mosquitoes over a particular landscape.

Then, multiple iterations of this process were

conducted by generating more resistance maps

via RF and subsequently re-calculating least

cost paths. As a result, the model refined itself

with each subsequent iteration, producing

increasingly accurate predictions of mosquito

genetic connectivity based on landscape data.

Compared to previous landscape genetic

models, one distinct advantage of RF is

its resistance to overfitting—the model

produced by RF is not overly sensitive to

noise in the data that it was trained on. To

test if their model overfit the data, Pless and

Amatulli conducted “leave-one-out crossvalidation,”

meaning that the model was run

thirty-eight times, each time leaving out one

of the thirty-eight genetic data points.

Results generated by this cross-validation

process were comparable to the results from a


model based on a full data set, demonstrating

that the model was not overfitting the data. In

fact, leave-two-out cross-validation was also

conducted, which further demonstrated that

the model did not overfit the data and could

accurately predict genetic distances.

But while this novel iterative approach

combined with RF did, in fact, prove to be

effective, it was initially time-consuming. To

address this, the researchers decided to use

GRASS—a geographic information system

software—in addition to R, a statistical

computing environment. “We wrote

everything first in R, but it was not fast enough

to do all the iterations, so then we used GRASS

to build cost paths analysis… and we conducted

the machine learning part in R, allowing us to

speed up the process from twenty-four hours

to one or two,” Amatulli said.

The researchers had successfully

constructed a model that predicted genetic

distances based on landscape data more

accurately than previous models. This

meant that they could track the movements

of A. aegypti mosquitoes based on the idea

that landscapes facilitating the animal’s

movements allow for greater genetic

connectivity. Inversely, they could also

consider the possibility that landscape

barriers result in greater genetic distances

due to lower movement. Interestingly, of the

twenty-nine environmental variables tested,

the researchers discovered that maximum

temperature was the most important in

predicting genetic connectivity, followed by

slope, barren land cover, and human density.

ABOUT THE AUTHOR

A Tool for Ecological Intervention

and Protection

The novel model of A. aegypti

landscape genetics is important because

it accurately predicts the genetic

connectivity—and thus the mobility—

of mosquitoes in regions where samples

were not taken and genotyped.

The broader implications of tracking

mosquitos with such accuracy involve

recently developed methods of disease

control. A prime example of this is releasing

genetically modified mosquitos that will

prevent wild mosquito populations from

reproducing. This kind of model provides

valuable knowledge about where the

mosquitoes should be released and how

far the intervention will spread. Another

potential application is demonstrating

the effects of pesticide application,

which would cause natural selection of

mosquitoes with pesticide-resistant genes.

In theory, the model could be used to

predict where those genes would prevail.

Beyond mosquitoes, this study—

with its iterative RF methods—is an

innovative step forward in the field of

landscape genetics. The novel strategies

that were employed could help protect

corridors for vulnerable animal

populations. “We hope this paper will be

inspiring to people, more broadly, who

are trying to control invasive species or

who are trying to protect endangered

species,” Pless said. ■

A R T B Y N O O R A S A I D

ELIZABETH WU

ELIZABETH WU is a first-year in Saybrook College. In addition to YSM, she is an intern for the New Haven

Public School Advocates through Yale's First Years in Support of New Haven.

THE AUTHOR WOULD LIKE TO THANK Evlyn Pless and Giuseppe Amatulli for their time and

enthusiasm about their research

FURTHER READING

Pless, E., Saarman, N. P., Powell, J. R., Caccone, A., & Amatulli, G. (2021). A machine-learning approach

to map landscape connectivity in A. aegypti with genetic and environmental data. Proceedings of

the National Academy of Sciences of the United States of America, 118(9), e2003201118. https://doi.

org/10.1073/pnas.2003201118

Bishop, A., Amatulli, G., Hyseni, C., Pless, E., Bateta, R., Okeyo, W. A., ... & Saarman, N. P. A machine learning

approach to integrating genetic and ecological data in tsetse flies (Glossina pallidipes) for spatially

explicit vector control planning. Evolutionary Applications. https://doi.org/10.1111/eva.13237

Zhao N, Charland K, Carabali M, Nsoesie EO, Maheu-Giroux M, Rees E, et al. (2020) Machine learning

and dengue forecasting: Comparing random forests and artificial neural networks for predicting

dengue burden at national and sub-national scales in Colombia. PLoS Negl Trop Dis 14(9): e0008056.

https://doi.org/10.1371/journal.pntd.0008056


FOCUS

Medicine

A BREAKTHROUGH TH

Could teplizumab lead us to a cure for typ

Before insulin was discovered in 1922

by Sir Frederick Banting and Charles

Best, type 1 diabetes—an autoimmune

disease that renders the body unable to

convert blood sugars to energy—was often a

death sentence. Patients with diabetes rarely

lived for more than two years after disease

onset. This discovery of the insulin treatment

was revolutionary: for the first time, patients

could survive and manage their illness.

Nearly a century later, a new

breakthrough in the field of type 1

diabetes has been achieved. A clinical

trial analysis published in Science

Translational Medicine, co-authored by

Kevan Herold, C.N.H. Long Professor of

Immunology and of Internal Medicine

at Yale University, and Emily Sims,

Assistant Professor of Pediatrics at

Indiana University, reported compelling

evidence for teplizumab—a drug granted

FDA ‘Breakthrough’ status in January

2021. The breakthrough aspect comes

from the fact that this drug doesn’t

simply address symptoms; it could be

able to preemptively delay, or even

prevent, type 1 diabetes altogether.

The journey towards teplizumab has

been a long and arduous one. “Literally

for the past thirty years I’ve been working

on this, from doing the pre-clinical mouse

work, to doing the early investigatorinitiated

clinical trials, to eventually

leading clinical trials that were done by

NIH consortia like the Immune Tolerance

Network or TrialNet,” Herold said.

A Long and Winding Road

Even after insulin started to be used as

treatment, Herold witnessed the drastic

effects that the disease had on the quality

of life of patients. “Diabetes is with you

twenty-four-seven,” he said. “There’s literally

nothing that you do that is not impacted by

having the disease, whether it’s deciding to

eat or not, whether it’s exercise, whether it’s

sleep, whether it’s going to class.”

For Herold, the prospect of conducting

research had been appealing since his

undergraduate years. Throughout his

research trajectory, he has always strived to

understand the basic mechanisms, causes,

and treatments of type 1 diabetes. Herold’s

decades-long commitment to the pursuit

of scientific advancement in this area began

even before the invention of many essential

research techniques scientists often rely on

today, such as polymerase chain reaction. “At

that time, a lot of what we take for granted now

hadn’t even been discovered,” he explained.

“Immunology was still in its infancy.”

The research leading up to this

breakthrough drug began in 1990

for Herold and his colleague, Jeffrey

Bluestone, Professor of Metabolism and

Endocrinology at UCSF. In his earlier

research, Herold had studied autoreactive

T cells—a group of immune white blood

cells that turn against our own cells and

tissues. By looking at them in mouse

models with diabetes, he was led to believe

that they could cause type 1 diabetes in

humans. With researchers at Johnson

& Johnson, Bluestone then developed a

human drug, teplizumab, that modifies

a certain population of autoreactive T

cells that play an important role in killing

beta cells—the cells that produce insulin

in the pancreas. CD3, a T cell receptor, is

involved in activating this population of

autoreactive T cells. Teplizumab is an anti-

CD3 antibody that binds competitively to

CD3—an action thought to prevent the

receptor from binding to and activating the

autoreactive T cells. Teplizumab thus serves

as a regulatory immunosuppressant for an

overactive immune system, protecting

against the depletion of beta-cells that is

characteristically seen in type 1 diabetes.

From Gold, to Dirt, and Back

Teplizumab showed early success in

Herold’s first clinical trial in 2002 and was

later acquired by biotechnology company

MacroGenics. It was also supported by

the pharmaceutical company Eli Lilly

in phase III clinical trials to evaluate its

safety and efficacy. However, this large-

PHOTOS COURTESY OF ALEX DONG


Medicine

FOCUS

ERAPY FOR DIABETES

e 1 diabetes?

BY ALEX DONG

scale trial did not end up meeting its

target efficacy endpoint, the necessary

threshold to move forward. “When

that happens in the pharma field, it’s

a disaster,” Herold explained. “You’ve

basically turned gold into dirt.”

MacroGenics and Eli Lilly both

abandoned the project in 2010, and

teplizumab was considered a failure.

“There was nobody willing to pick it up,

and we had no support,” Herold said.

Knowing that the drug development

process requires substantial resources,

Herold and his colleagues traveled across

the country and even flew internationally

to Germany in pursuit of funding and

support. Despite teplizumab having

favorable mouse and human trial data,

every company, foundation, or potential

investor declined—for eight years.

Finally, in 2018, Provention, a

biotechnology company founded just

two years prior, decided to take on

teplizumab anew. Herold cites his belief

in the promising science behind the

mechanisms of the drug in humans as a

large motivating factor in his persistence

over the eight long years. “This was

literally dead,” he said. “It just goes to

show you that if you think something

is really worth doing, you [have] got to

stick with it no matter how bad it seems,

because one turn of the tide could make

all the difference in the world.”

In 2019, Herold led a phase II clinical

trial, sponsored by TrialNet, testing the

effectiveness of teplizumab. He found

that it successfully delayed the onset of

type 1 diabetes in high-risk patients by

approximately two years. Herold then

proposed a new question: how does


teplizumab affect beta-cell function?

“We ask this question all the time in

people who have diabetes, but we really

never had the opportunity to answer it in

people at risk for diabetes,” he explained.

“They don’t yet have the disease, but we

know that they’re going to develop it.”

Delaying the Onset of Diabetes

For Sims, conducting research was not

always a priority. “I always thought I wanted

to be a doctor, and I always loved kids, so I

thought I was going to be a pediatrician,”

Sims said. She found the physiology of

endocrinology interesting and intuitive,

so she decided to specialize in pediatric

endocrinology. She was first exposed to

basic science research during these years.

Almost immediately, the inherent crossapplications

of research and medicine

became apparent. “Working in the lab

gave me this really cool opportunity to

ask questions that were relevant to what

you see in the patients you’re treating,” she

said. Referencing a line from Aaron Burr in

the musical Hamilton, she explained that

research is like “being in the room where it

happens.” In Sims’ many interactions with

children diagnosed with type 1 diabetes,

she witnessed the toll of this disease on her

patients and their families. “When you get

that diagnosis, your life changes,” she said.

Herold and Sims are both involved in the

NIH consortium TrialNet. Sims’ expertise

studying beta-cells and analyzing metabolic

data drew her to join Herold in pursuit

of a better understanding of the effects of

teplizumab on beta-cell function.

In their 2021 study, published in Science

Translational Medicine this March,

Sims and Herold suggested that there

is progressive depletion of beta-cells

in the years preceding type 1 diabetes

diagnosis. During this period, the level

of metabolic dysfunction, which is a sign

of autoimmunity, defines the stages of

the disease. Stage 1 consists of the period

before glucose abnormalities arise; stage 2

makes these abnormalities more evident;

and stage 3 is the typical definition of

diabetes—the phase defined by clinical

presentation of high blood sugar.

Sims and Herold investigated whether

teplizumab would delay stage 3 clinical

diagnosis in seventy-six individuals at

stage 2 of the disease. They found that a

single fourteen-day teplizumab treatment

program could have enduring effects: the

teplizumab group had a median time of


FOCUS

Medicine

five years before stage 3 onset compared to

just two for the placebo group. Moreover,

eighteen percent of teplizumab-treated

individuals treated were not diagnosed

with stage 3 at all in more than five years,

which is the time during which followup

data was being collected, compared to

just six percent for the placebo group. The

study also found that teplizumab improved

beta-cell function, even in individuals who

did not develop diabetes. The drug could

also reverse declines in insulin secretion.

Sims and Herold’s paper outlined

that teplizumab led to an improvement

in metabolic responses and delay of

diabetes. It is the first drug of its kind

to ever do so. “If you’re eight years old

and get treated for the disease, you’re

not going to develop it for five years

until you’re thirteen,” Herold said. “The

maturation of a child during that period

of time is extensive, and you’re probably

better able to manage the disease when

[you’re] older. Same thing if you’re going

into middle school and you’re not going

to get it until after graduating high

school. That’s a big deal!”

A Game-Changer

The Food and Drug Administration

(FDA) has recently granted teplizumab

“Breakthrough Therapy Designation,”

which bodes well for its approval this

summer. If the drug is approved, an

important next step is to identify those

who are eligible for and could benefit

from the treatment. Sims explained that

TrialNet screens the relatives of patients

with diabetes, but most people who

develop diabetes do not actually have

family members with the disease. “We

have to think big: now we have a reason

to screen people at risk for diabetes,

because there is something we can do

about it,” Herold stated.

Current insulin treatments act as

retroactive “band-aids,” making it

possible for diabetes patients to manage

their symptoms and survive. Teplizumab,

on the other hand, targets the underlying

mechanisms of type 1 diabetes before its

onset. This means that it could modify

the disease’s trajectory. With teplizumab,

the playing field for type 1 diabetes has

completely shifted—what was once a

waiting game now holds options for

delay, or even prevention, of the disease. ■

A R T B Y S O P H I A Z H A O

ABOUT THE AUTHOR

ALEX DONG

ALEX DONG is a first-year student from Canada in Benjamin Franklin college interested in studying

Biomedical Engineering on the pre-med track. On YSM, Alex is a copy editor, staff writer, layout designer,

photographer, and artist. Outside of YSM, Alex is a Senator for the Yale College Council and a poet for

the Yale Layer.

THE AUTHOR WOULD LIKE TO THANK Dr. Kevan Herold and Dr. Emily Sims for taking the time to

discuss their experiences and research with him.

FURTHER READING

Herold, K. C., Bundy, B. N., Long, S. A., Bluestone, J. A., DiMeglio, L. A., Dufort, M. J., ... & Greenbaum, C. J.

(2019). An anti-CD3 antibody, teplizumab, in relatives at risk for type 1 diabetes. New England Journal

of Medicine, 381(7), 603-613.

Sims, E. K., Bundy, B. N., Stier, K., Serti, E., Lim, N., Long, S. A., ... & Type 1 Diabetes TrialNet Study Group.

(2021). Teplizumab improves and stabilizes beta cell function in antibody-positive high-risk individuals.

Science Translational Medicine, 13(583).


Electrical Engineering

FOCUS

GENERATING

RANDOMNESS

A Laser-Based Scramble

for Random Numbers

Introducing a new mechanism, a hundred times faster than before

BY ALEXA JEANNE LOSTE

ART BY ELAINE CHENG

When you play the violin, you can trace back its sound to the vibration of its

strings. These energy vibrations—the sound waves—transfer from the strings

to the violin’s bridge, and then to its body, eventually vibrating the air before

reaching our ears as sound. The hollow wooden body serves as a resonator for acoustic

waves. Its shape is tailored to resonate with many acoustic frequencies, producing the rich,

resonant quality of sound that we appreciate as music.

This is how Hui Cao, John C. Malone Professor of Applied Physics and of Physics at

Yale, explained the design of a new laser developed in her lab. Her team is leveraging this

innovative technology to generate random numbers at revolutionary speeds.

In an article published in Science on February 26, Cao and her collaborators wrote about

their new laser design with a random bit generation (RBG) rate of two hundred fifty terabits

per second—faster than existing versions by more than a hundredfold. Functioning by

a completely different mechanism, their laser uses many different channels to generate

random numbers in parallel, while increasing the RBG rate of each individual channel.



FOCUS



The potential of their basic research to be leveraged into concrete applications inspires the team to continue studying the complex physics of laser dynamics, Cao said.

Like the sound waves produced by a violin

string that are amplified in the wooden

body, the laser produces light waves that

are amplified in an optical resonator, which

Cao designed in a bow-tie shape. This shape

allows the laser to resonate with many optical

modes of different frequencies, analogous to

the multiple tones of a violin string. “The

breakthrough is a different mechanism,” Cao

said. Whereas conventional lasers only have

one or a few modes, the many modes of this

new laser can interfere with each other to

create complex spatio-temporal patterns—

which is where the randomness originates.

Leveraging Lasers for Cybersecurity

Doing basic research in understanding

complex laser behaviors opens up the

possibility for a multitude of applications,

some of which come in unexpected forms.

“The original goal was not generating

random numbers, but just changing the

shape of the cavity and studying the laser

dynamics,” said Kyungduk Kim, a graduate

student in Cao’s group. Cao explained

that by working with more complex laser

designs, her lab is tapping into potential new

functions of lasers. “Lasers are probably one

of the most important inventions in science

and technology in the last century,” Cao said.

Among all the potential applications

of lasers, random number generation

represents a particularly important one. In

a world increasingly dependent on digital

communication and exchange, random

number generation is integral to ensuring

online security. One ubiquitous example is

in the creation of encryption keys—used

to scramble private information such as

passwords, banking information, or messages

to prevent them from being intercepted

when sent through online channels, like

emails. The random quality of the selected

key is integral to preventing potential

attackers from breaking into messages and

stealing information. Predictable keys, or

even keys based on sophisticated algorithms

whose pattern can be uncovered, could leave

sensitive private data vulnerable.

Additionally, random numbers have

a variety of applications in scientific

research. The modelling of stochastic

processes that involve random

probabilities, such as the spreading of

viruses or fluctuations in the stock market,

relies on streams of random numbers that

can simulate the unpredictability of these

systems. Statistical analysis also relies on

random number generation to choose

random samples from a population in

order to prevent biases that may make

the analysis less reliable.



FOCUS

Laser-to-Randomness Fundamentals

Not even the most powerful supercomputer

can generate true random numbers on its

own. This is because computers run on

algorithms, and any finite algorithm will

eventually loop back and repeat itself, yielding

a specific pattern of outputs. To generate true

randomness, one has to rely on external

physical sources of entropy, or naturally

occurring disorder in the universe. Through

monitoring systems that have dynamics that

cannot be predicted, they can be used as a

source of randomness. One way that scientists

have done this is by using lasers.

Light waves in the lasers that the researchers

work with, called broad-area semiconductor

lasers, often naturally experience irregular

fluctuations from the interaction of light with

the lasing medium. Previously, researchers

leveraged this property of light as a source

of randomness, translating fluctuations

of light intensity into zeros and ones. The

randomness comes from the chaotic pattern

of the stream of bits generated. However,

there is a limit on how quickly those lasers

can generate random number streams. This

depends entirely on how fast the fluctuations

occur. To increase the RBG rate of a laser

beyond that limit, one would need to either

increase the number of bit streams generated

in parallel or use a new mechanism as a source

of randomness that has faster dynamics. The

Yale team’s new laser does both.

Improvements in Quantity and Quality

Previously implemented lasers had flat

edges. With this conventional shape, laser

intensity fluctuations were correlated

with both time and space, limiting the

lasers’ effectiveness: correlations over time

decrease the quality of the randomness

sampled from a single location, and

correlations over space decrease the

number of different locations one could

measure to get random numbers.

By curving the edges of the laser cavity,

Cao and her collaborators were able to

substantially increase the number of lasing

modes (think: violin string tones). “When

you have this curved edge, the light can

come out at many different spatial locations,”

Cao said. “When you measure the intensity

at each spatial location, these intensities

will fluctuate in time.” By recording output

from multiple positions simultaneously,

they could use the laser to generate multiple

random number streams in parallel.


In addition to inducing multiple

RBG streams at once, the new laser also

enhances the random bit generation rate

of every individual stream by using a new

mechanism. Whereas conventional chaotic

lasers rely on the irregular fluctuations on

a time scale set by their response time to

extract randomness, the research team’s laser

uses a different source of randomness: the

interference of the multiple lasing modes.

Since the light waves in each mode have

different frequencies, by summing them up

at different points in space and time—that

is, their spatio-temporal interference—

the researchers could use the variation

in interference intensity as a source of

randomness. Because the interference

pattern fluctuates much faster than the

emission from chaotic lasers, it can generate

random numbers at a much faster rate.

Breaking into a New Field

Cao mentioned that this project was her

lab’s first venture into the field of random

number generation, and they did not have

any previous experience or connections to

other researchers in the field. Having realized

that her work could be applied to a new

mechanism for random number generation,

she assembled an interdisciplinary team

to study techniques including translating

measured intensities into digital bits and

quality testing random numbers. “We

learned a lot through this adventure, and I

think that is how scientific research gives us

a lot of surprises. And sometimes, we also

get some reward,” Cao said.

To get published in a scientific journal,

every article must undergo a thorough

review process in which peer researchers

in the field must provide feedback on the

work. “The reviewers of our papers …

were very critical and made sure we did

everything right,” Cao said. “On the other

ABOUT THE AUTHOR

hand, they really helped us by suggesting the

additional tasks we need to do to convince

people our method works.” Cao cited the

support received from the random number

generation community, which was helpful to

her team as they broke into the field.

Kim also attested to the important role

of collaboration in the project. “It was

very lucky that I met good collaborators,”

Kim said. Researchers from Nanyang

Technological University in Singapore

built the lasers that the Yale team designed,

which are cutting-edge chip-scale lasers

fabricated on a semiconductor wafer. Kim

also emphasized that his work directly built

upon the work of previous researchers in

the lab, highlighting the cumulative process

of building knowledge in the scientific field.

Scaling Down to Scale Up

Looking forward, the next challenge facing

this new laser is integrating the system into a

smaller medium, such as a chip. In this study,

to measure the spatiotemporal interference of

the light waves (the source of randomness), a

special camera was used. This streak camera

measured the light emission at an extremely

rapid rate, recording an image of the emission

every picosecond, resulting in one image

produced per every trillionth of a second. A

resolution this high comes with a steep cost,

so the camera is primarily used by researchers.

Additionally, its bulkiness presents a hurdle

to wide-scale adoption. Taking the new laser

forward would require engineering laser

chips with integrated photodetectors.

Nevertheless, the work done by the Yale

researchers takes the field of random number

generation a step forward—or in this case,

two whole orders of magnitude forward.

For Cao, the potential of basic research to be

leveraged into concrete applications inspires

the team to continue studying the complex

physics of laser dynamics. ■

ALEXA JEANNE LOSTE

ALEXA JEANNE LOSTE is a first-year prospective Molecular Biophysics & Biochemistry major in Ezra

Stiles College. In addition to writing for YSM, she is a project head for GREEN at Yale, a member of the

Environmental Education Collaborative, the STEM Panel Chair for the Conference Committee of the

Women’s Leadership Initiative, and a copy desk staffer at the Yale Daily News.

THE AUTHOR WOULD LIKE TO THANK Kyungduk Kim and Dr. Hui Cao for their time and enthusiasm

in sharing their research.

FURTHER READING

Kim, K., Bittner, S., Zeng, Y., Guazzotti, S., Hess, O., Wang, Q. J., & Cao, H. (2021). Massively parallel

ultrafast random bit generation with a chip-scale laser. Science, 371(6532), 948-952.


FOCUS

Physics

BY BRIANNA FERNANDEZ

ART BY ALEX DONG

THE RADIO

STATION AT

THE END OF

THE UNIVERSE

Chasing the axion to unravel the

mystery of dark matter



Physics

FOCUS

The matter we interact with on

a daily basis is known as normal

matter. Counterintuitively, this

normal matter makes up only about

five percent of the universe. Physicists

think the rest is composed of two other

constituents: dark energy, the force

thought to be speeding up the expansion

of the universe, and dark matter, an

unknown type of matter that only

interacts strongly with gravity. Though

neither of them can be detected directly,

the role that dark energy plays in the rate

of the universe’s expansion, as well as the

effect that dark matter has on galactic

structure, make physicists confident in

these hypothesized substances.

Some people wonder how galaxies

rotate at a seemingly impossible rate; in

theory, they simply could not maintain

such high speeds given the masses we

detect from Earth. From the perspective

of astronomers, galaxies’ low masses

could not generate enough gravity to hold

them together. Something is giving them

extra mass—something undetectable.

This is what we have designated dark

matter. But what is dark matter, really?

What is it made of? Enter the axion.

Researchers at the Yale Department of

Physics’s Wright Laboratory have come

together in pursuit of the axion. By looking

for this hypothetical particle—which is

thought to comprise dark matter—they

think it could be possible to find dark

matter. Led by fifth-year graduate student

Kelly Backes, this group recently published

a paper in Nature that reports the use of

vacuum squeezing to double the search

rate for axions. This process enabled them

to circumvent the quantum limit that many

dark matter searches can barely approach.

By breaking through this limit, rather than

merely approaching it, they are ushering in

an age in which searches for fundamental

physics are less hindered by noise, bettering

the chances of the axion’s discovery.

Hiding in Plain Sight

This question of missing galactic mass

has been pondered by physicists since the

1930s, resulting in a variety of potential

candidates

for what dark matter

could be. “Because there are so many

different options for what could be

dark matter, a lot of the well-motivated

theories are particles or theories that

solve multiple problems,” Backes said.

“There are very few things in physics that

just exist for one weird purpose.” One

promising dark matter candidate is the

axion—a hypothetical particle that was

first proposed in 1977 by Roberto Peccei

and Helen Quinn. Named after a laundry

detergent, the axion was theorized to solve

the strong charge-parity (CP) problem of

quantum chromodynamics—a problem

within the Standard Model of particle

physics in which two fundamental

nuclear forces act differently. Later,

researchers Steven Weinberg and Frank

Wilczek suggested that the axion could

also be what makes up dark matter.

Although axions are theorized to be

infinitesimally small and extraordinarily

light, they completely pervade the space

which they occupy, existing everywhere

and all the time. Their omnipresence

makes it more convenient to imagine

each axion as a sea of particles that

oscillate together rather than as

individual ones. With this knowledge in

hand, the detectors searching for axions

aim to sense them as waves.

While we generally think of dark matter

in the context of its interactions with gravity,

since this is the only way in which we know

it exists, dark matter seems to have feeble

interactions with other fundamental forces.

As a result, some scientists looking for

axions do so by detecting their extremely

weak interactions with electromagnetism.

“If you supply a magnetic field, the axion

field and this magnetic field interact and

produce a tiny [bit of] excess electric field

that is actually then detectable, and that's

the interaction that we center our detector

around,” Backes said. Essentially, axions

are detected as excess power in

a detector. They react with

magnetic

f i e l d s ,

yielding small traces of electric field. It is

Backes’s job to amplify this electric signal

and, from there, detect these evasive axions.

The Great Cosmic Radio

Backes’s research group has spent years

searching for this dark matter candidate,

analyzing excess power that could be

produced by axion waves and a large

magnetic field in the hopes of finding

the answer to this long-held mystery.

“Essentially what we’re doing is operating a

really, really, really sensitive radio,” Backes

said. The interactions they measure occur

inside of a microwave cavity, or a resonator,

and when the resonator frequency matches

that of the axion field, the interaction is

enhanced, amplifying the signal.

When you’re flipping through radio

stations in the car, you’ll tune to a station,

listen to hear if that’s what you want, and

tune to the next station until you find what

you’re looking for. However, your radio

will only pick up a station if it is tuned to

the same frequency as the incoming radio

waves. In this case, the detector functions

similarly to the car radio, and the axion is

the station to be detected.

But where exactly is the axion station

located? As it turns out, it is hard to tell.

“You’re tuning through frequency space, and

you’re looking for the only station in the

universe, and you have no

idea where it is,”

Backes said.

For now,



FOCUS

Physics

Backes’s

group is searching

for axion frequencies at around

four or five gigahertz, but the axion

could be hiding anywhere on the range

of hertz to terahertz—where a frequency of

one hertz is one cycle per second, and one

terahertz is a trillion times that.

Though the range Backes and her

colleagues are investigating is small relative

to the orders of magnitude of potential

frequencies that surround it, it is strongly

grounded in theory. Some groups of

theorists have done large-scale calculations

that indicate that the axion’s location is

likely around the range they are exploring.

Experimentally, this range is favorable

because the low gigahertz range makes

for a nicely sized detector: resonator size

is proportional to desired frequency, so a

much lower frequency would require an

inconveniently large detector. A higher

frequency, conversely, would necessitate an

exceptionally smaller one.

The Coolest Part: Vacuum Squeezing

The vacuums physicists use are nothing

like the loud cleaning appliances with

which most people are familiar. In physics,

a vacuum is the absence of matter and

energy. It is the ground state of all fields

in quantum mechanics, and its energy

fluctuates in quantum fluctuations, creating

temporary random changes of energy

in a point in space. Vacuum squeezing

redistributes these fluctuations, enhancing

or repressing them along different time

intervals. “I think I’m biased, but this is the

coolest part of what I’ve done,” Backes said.

When conducting any experiment,

data is likely to come with noise, which

is a result of random variations that

interfere with the signal. Like radio

static, the electronic noise in axion

experiments

doesn’t

h a v e

any specific frequency or phase

preference. Since that noise is made of

components with different phases, one

could mathematically decompose it into

terms of more traditional sine and cosine

wave patterns. The amplitudes of these

sine- and cosine-like components of these

fluctuations don’t commute, which is why

the noise exists in the first place. “Like

the traditional uncertainty relationship

between position and momentum, you

can't measure all fluctuations at once

without adding noise to your system,”

Backes explained. “That's where these

quantum vacuum fluctuations come in.”

However, it does not matter whether all

the phases can be precisely measured in the

detector—the way that axion signals are

measured does not necessitate it. Instead,

physicists squeeze the noise into one

“quadrature,” like position and momentum

in the previous example, meaning that the

sine- and cosine-like fluctuations would be

two measurement quadratures.

If we were to think of noise as a malleable

ball, squeezing it would involve taking a

round noise state that lacks phase preference

and processing it with an amplifier so that

it is squeezed into an oblong blob of a noise

state—one that has a phase preference. The

resonator’s power has no phase preference,

so when the newly squeezed state is guided

into its cavity, the axion is measured until

it no longer has a phase preference either.

Essentially, one axion arrives, displacing

the squeezed state in one direction, and

another follows, displacing it in a different

direction. This process molds the squeezed

state, and the pattern continues until it is

broadened by the displacement.

Once the squeezed state is slightly

fattened, it is read out of the microwave

cavity and squeezed in the opposite

direction. Flattening the squeezed state

amplifies the hypothetical axion signal

IMAGE COURTESY OF LAUREN CHONG

The upper plates of the experiment's dilution

refrigerator at the Lamoreaux Group.

along the newly shaped quadrature,

which is the same quadrature that

originally had the squeezed noise.

Ultimately, this allows Backes and her

team to measure an amplified signal

against subquantum limited noise,

making it easier to detect axions.

This work is revolutionizing the field,

which should make the search for axions

more efficient. “I think the big impact of

this specific paper and this work is it shows

for the first time that quantum squeezing

can be used as a tool to speed up a fullscale

fundamental particle search,” Backes

said. As the first experiment to show that

one can look for new fundamental particles

against a noise background that is below

the standard quantum limit, this work is at

the forefront of the search for dark matter.

Dark matter has eluded physicists for

decades, but Backes and her team might

have unearthed a faster path to find it

with their novel approach to detecting

the axion. They have not had luck

yet, but their research takes time.

For now, they can only continue

flipping through galactic radio

channels, hoping to find the

station at the end of the

universe. ■

ABOUT THE AUTHOR BRIANNA FERNANDEZ

BRIANNA FERNANDEZ is a sophomore in Pierson College studying astrophysics. In addition

to writing for YSM, she is one of the magazine’s copy editors. Outside of YSM, she researches

exoplanets with Professor Debra Fischer and advocates for free prison phone calls with the

Yale Undergraduate Prison Project.

THE AUTHOR WOULD LIKE TO THANK Kelly Backes for her time and enthusiasm to share her research.

FURTHER READING

Backes, K. M., Palken, D. A., Al Kenany, S., Brubaker, B. M., Cahn, S. B., Droster, A., ... & Wang, H. (2021). A

quantum enhanced search for dark matter axions. Nature, 590(7845), 238-242.e


ASIA

ASSESSING SOCIAL IDENTITIES

T

he various groups we belong to are at the heart of our human

identities. These social identities shape who we are and

influence everything from our individual actions to our shared

interactions. We behave in accordance with the norms of the groups we

identify with, with group memberships that are dynamic. This means

that our social identities are context-dependent; at any moment, the

group membership that is psychologically salient for a person can

change. In other words, our actions and interactions often conform to

the norms of the group we identify with at a particular instance.

This prompts questions about our social identities: what factors

determine which groups we identify with? How do we switch between

our different identities, and how do we deal with competing identities?

The major roadblock to studying these concepts is that social identity

salience is difficult to assess, especially in a natural setting. Researchers

face obstacles and uncertainties in determining which identity is guiding

someone’s actions and interactions at a given moment.

In a creative attempt to address this, researchers from the

University of Exeter in the United Kingdom recently developed

an analytical protocol, ASIA (Automated Social Identity

Assessment), that uses linguistic indicators in text to infer salient

group membership at a particular moment.

“Salience is a very dynamic thing, so it can switch very quickly,”

said Miriam Koschate-Reis, the lead researcher for this project. “If

my little girl runs through here, then I can very quickly switch to

being a parent and back to being an academic. It’s very fast switching,

and we haven’t really looked much at these switches.” (Ironically,

seconds after she said this, her little girl did run through the room.)

In the past, researchers have attempted to use self-reporting as a way

of assessing salient social identity. However, self-report measures are not

very useful for studying temporal dynamics of social identities in natural

settings, nor are they reliable for studying long periods of time, because

they provide relatively limited datasets. Additionally, if someone is

asked to self-report their “main” social identity at a particular moment,

they may lack the introspection to actually answer the question. For

example, take a moment now to try to identify your salient social

identity—student, feminist, daughter, etc. It is quite difficult.

In contrast, ASIA relies on computational linguistics and uses a

binary classification model in order to determine which of two

social identities is salient in a person at a particular moment. ASIA

makes use of linguistic indicators, because sociolinguistic theories

assert that both vocabulary and stylistic choices are affected by social

variables and groups. Linguistic information has been established as

a reliable way to determine group classification and identification.

Additionally, there is a wide availability of useful data in the form

of written text in online forums, which makes models that focus on

linguistic styles convenient and desirable.

However, this data use doesn’t come free of concerns. While

developing the ASIA protocol, the researchers made sure to

center ethical considerations—mainly the ethical implications

of assessing specific social identities in the first place, as well as

of using online data to train and validate the model.


Psychology

BY TEJITA AGARWAL

ART BY MALIA KUO

FEATURE

“It’s quite tricky when you’re almost looking into people’s

minds. . . . that’s why we really felt strong about writing and

putting ethics first to say, if you want to develop this tool, please

think carefully about the ethics of it,” Koschate-Reis said.

Koschate-Reis and colleagues concluded that researchers have

a responsibility to consider any foreseeable harm to individuals,

especially those whose identities may expose them to discrimination

and ostracism. They explained that public online forums are perhaps

a more ethical source of data than social media platforms where

users face difficulty or confusion in selecting appropriate privacy

settings. Public online platforms generally have anonymous users

with little personal identifying information.

After training and testing their program, the researchers concluded

that ASIA provides a mechanism to assess salient social identities using

naturally occurring data at a scale large enough to investigate salience

within a person over time. This step is essential in investigating how

people switch between different identities and when those identities

come about. For example, consider: when does someone start to

identify themselves as a parent? Is it when they become aware of

pregnancy, when they are buying child-raising materials, or when the

baby is actually born? The ASIA protocol gives researchers a reliable

way to seek answers to these questions, furthering the general effort

to learn about our social identities in natural social settings. ■

Koschate, M., Naserian, E., Dickens, L., Stuart, A., Russo, A.,

& Levine, M. (2021). ASIA: Automated social identity

Assessment using linguistic style. Behavior Research

Methods. doi:10.3758/s13428-020-01511-3


FEATURE

Microbiology

MEMORIES OF A BRAINLESS

SLIME MOLD

THE LITTLE SLIME THAT COULD

Let’s talk about slime.

And no, not the kind that went viral on ASMR TikTok.

Today, we’re diving deep into the world of Physarum

polycephalum, an intelligent unicellular eukaryote with the

ability to solve complex problems, and how it is changing our

perception of memory one tube at a time.

The concept of memory is often associated with complex

organisms: humans reminiscing about failed family picnics or

those heartfelt videos of dogs jumping into the arms of their

owners after years of separation. We love to see it. But it turns

out that the conceptualization of memory may be different from

what most expect. Researchers Mirna Kramar and Karen Alim

at the Max Planck Institute for Dynamics and Self-Organization

and the Technical University of Munich recently investigated

Physarum and the way it encodes memory of food sources

through rapid communication between its tube systems.

Spoiler alert—and apologies to the viral military dog reuniting

clips—Physarum is coming for your brand.

Physarum is a network-shaped organism that explores its

environment with a vast array of tubes, rapidly and constantly

reorganizing its body plan to pin down a food source, all while

maintaining the ability to find the shortest possible path between

nutrients. Yet, even though Physarum seems like just another slime

mold, Kramar chuckles at the memory of working with the organism.

“Physarum is extremely dynamic and very, very moody. It

really doesn’t like being under the microscope. It will run away,

actually physically run away. It’s hilarious,” Kramar said.

Kramar began working with Physarum years ago at the

beginning of her PhD, carrying out various exploratory

projects and recording observations about this capricious

creature. During one of these observatory studies, she noticed

that Physarum was running to the edge of the petri dish.

Not wanting the experiment to conclude with Physarum

committing scientific death through a heroic escape, Kramar

attempted to lure it back down with a food source.

It worked. After Physarum consumed the food source and

began moseying elsewhere, Kramar noticed that a circular

arrangement of big tubes had formed exactly where the

food source was. And this tube imprint didn’t fade, even

after Physarum continued its journey around the petri dish.

“Observing this I had two questions: how does this imprint

come around in the first place, and is it useful?” Kramar said.

The researchers began observing the changes in tube diameter

before and after the addition of a food stimulus, finding that

there was an internal redistribution of mass: tubes closer to the

food got much larger, whereas peripheral tubes became smaller.

BY MALIA KUO

ART BY ANASTHASIA SHILOV

And even long after the stimulus had been consumed, the larger

tubes remained enlarged. But how did this happen?

They found that the propagation of tube dilation across the

network was mediated through a cytoplasmic flow, which

carried a chemical agent that softened the tube walls. This

cytoplasmic flow is critical to Physarum, transmitting both

nutrients and information through chemical signaling.

After determining that the propagation was due to cytoplasmic

flow, the researchers asked the second main question: does the

observed imprint constitute memory?

Hypothesizing that the tubes could represent Physarum’s

memory, given that they remained as an imprint even after

the stimulus disappeared, the researchers analyzed three

large tubes in a sample of Physarum. One tube was directly

connected to a group of tubes arranged in fan shape to forage

towards the bottom of the microscopic window. When Kramar

placed a food stimulus towards the top of the sample, that

tube attached to the fan got increasingly small whereas the

two tubes closer to the stimulus increased in size. This was

critical evidence for the memory of Physarum. “The selection

of which big tubes are important shows something more than

just an imprint or a remnant of the stimulus,” Kramar said.

Ruminating on the impact of this discovery, Kramar

discussed the potential implications of Physarum on primitive

memory. “This reminded us of synaptic plasticity and synaptic

facilitation, creating long-term memories from short-term

memories. That’s very interesting because Physarum has some

kind of very primitive membrane potential going on that we

don’t know much about,” Kramar said.

Of course, the implications of Physarum’s memory don’t

end with this project. Kramar predicts potential impacts on

fields such as soft robotics. Although the concept is still in its

beginning stages, she proposes that Physarum’s self-navigation

based on attraction to chemical stimuli could be used to guide

technological advances in arterial surgeries. For example, robots

could be designed to crawl and adapt to the arterial environment,

following a chemical stimulus that the condition creates.

So yes, maybe we can all have a little bit of Physarum within

us someday. ■

Kramar, M., & Alim, K. (2021). Encoding memory in tube

diameter hierarchy of living flow network. Proceedings of

the National Academy of Sciences of the United States of

America, 118(10), e2007815118. https://doi.org/10.1073/

pnas.2007815118



Physics

FEATURE

BRIDGING THE QUANTUM GAP

A NONLOCAL QUANTUM GATE CLOSES THE GAP

TO DISTRIBUTED QUANTUM COMPUTERS

BY YU JUN SHEN

ART BY TAI MICHAELS

Quantum computers may one day solve difficult problems, but

currently they still face many hardware limitations. Quantum

physics—the science of the very small, such as electrons and

photons— allows for “qubits” that can represent “0” and “1” at the same

time, a concept known as superposition. This gives them exponentially

faster processing speeds than traditional computers, which use binary

electrical bits assigned a fixed value of either “0” or “1.”

However, today’s quantum processors can only work with a few

qubits, compared to the billions of transistor bits in traditional

computers. To increase the number of qubits involved, researchers

from the Max Planck Institute of Quantum Optics in Germany have

demonstrated a distributed quantum logic gate that can connect

multiple quantum processors. Severin Daiss, Gerhard Rempe, and

colleagues set up two qubits, located sixty meters apart in two labs,

to interact using an additional photon sent between them. Quantum

logic gates like this are the quantum version of classical logic gates,

performing specific operations to input qubits. Researchers hope

having a distributed setup—where the quantum logic gate is not

necessarily in one location only—provides a more flexible, modular

approach towards achieving larger quantum computing power.

Using the distributed gate, the German researchers produced pairs

of maximally entangled qubits known as Bell states. Entangled qubits

can be highly correlated even though they are physically apart. Such

“spooky action at a distance,” as Einstein remarked, actually provides

quantum computers with their potential power. If one element in a

pair of Bell state qubits is measured, the other qubit’s condition is also

fixed, no matter how

far away.

In an ordinary

computer, billions of

transistors work in

unison to perform

logical operations—

such as addition,

multiplication

and information

processing—on

electrical bits.

Quantum researchers

have adopted a

similar approach to

quantum computing

(among other

methods) to design

“quantum circuits.”

IMAGE COURTESY OF WIKIMEDIA COMMONS

IQM Quantum Computer in Finland. A large

part of quantum computers is the cooling

system, in order to minimize thermal noise.


Quantum circuits

manipulate qubits,

which, in contrast to

electrical bits, are not

a fixed “0” or “1.” The circuits therefore require quantum logic

gates instead of the silicon chips found in ordinary computers.

As an example of a nonlocal operation, Daiss and Rempe performed

a quantum controlled-NOT (CNOT) gate in their experiments. The

CNOT gate uses the input of one qubit to determine whether or not

to invert the input of a second qubit. In many quantum circuits,

CNOT gates are used to achieve the superposition necessary for any

potential quantum advantage over classical computing.

Daiss and his colleagues placed two optical cavities containing a

rubidium atom in two separate rooms within a building at the Max

Planck Institute. In order to perform a quantum logic gate between

the two devices, the researchers first launched a photon towards the

first optical cavity along an optical fiber, then directed the reflection

to the second cavity (in the other room). The reflection caused an

interaction between the photon state and each atomic qubit state.

Following the photon measurement, with the addition of a Z-gate—a

type of quantum logic gate—on the first cavity controlled by a classical

communication channel, Daiss and his team completed a CNOT gate.

“Our experiment is the first that does such a gate between qubits

residing in completely independent laboratories,” Daiss said.

The team reported results of up to eighty-five percent accuracy

for the CNOT operation, at a computation rate of one kHz. While

this is low compared to current state-of-the-art quantum hardware,

the approach holds promise for a modular approach to scaling up

quantum computers. Qubits are much more fragile than electrical

bits; the slightest measurement by environmental disturbances

(dust, air, stray light) could break the trance. As qubits typically

reside in dilution fridges or vacuum chambers—which have limited

space—increasing qubit number requires denser packing. This

can cause problems like crosstalk noise and limited access to each

individual qubit, complicating manipulation and measurement.

Thus, in the future, instead of just increasing just the number of

qubits in a single processor, researchers may connect multiple

quantum devices using distributed quantum gates to improve

computational power. “Such a modular approach might open a new

development path for larger quantum computers,” Daiss said.

The researchers think that their protocol with the use of a

separate photon may be applied to other quantum operations

and gates between distant qubit modules. In a future quantum

computer, it is likely that many quantum gates—such as the

CNOT—will be involved, each with its own chance of failure.

Thus, the photon’s ultimate arrival would signal a successful

quantum operation, before subsequent operations proceed. ■

Daiss, S., Langenfeld, S., Welte, S., Distante, E., Thomas, P.,

Hartung, L., Morin, O., Rempe, G. (2021). A quantum-logic

gate between distant quantum-network modules. Science,

371(6529), 614-617. doi:10.1126/science.abe3150


FEATURE

Artificial Intelligence

BEAUTY IS IN THE EYE OF THE BEHOLDER

BY LAUREN CHONG

ART BY CECILIA LEE

Left. Right. Left. Right. We’re

swiping on Tinder, a social

network dating app where

users swipe left on users they find

unattractive and right on users they

find attractive. During these splitsecond

glances at pictures, we know

instantly when we find someone goodlooking.

Generally, when we make these

judgements about others, we do not


think about the specific attributes that

make them attractive. Our individual

preferences for beauty all come down

to subtle subconscious preferences in

our minds shaped by sociocultural

influence, background, age, and gender.

How, then, do we define beauty?

Researchers at the University of

Helsinki designed an innovative method

at the intersection of computer science

and psychology to investigate the

human brain and its interpretation of

attractiveness. With novel generative

brain-computer interfaces (GBCI)

technology, psychologist Michiel Spape

and computer scientist Tuukka Ruotsalo

studied the computer’s potential to

identify facial features that participants

consistently found attractive, as

measured by spikes in brain signals. With

this data, the computer then generated

new images of faces that the participant

was likely to find attractive, thus

interpreting each individual’s personal

preference based on brain signals.

“The point is that most of computer

vision and AI is busy with the question

of detecting what is in a picture: who’s

the person, what kind of person is it,

and so on. Our work is focused on

how humans respond to the picture,

what feelings are evoked in them, and

what kind of subjective perceptions do

different individuals get from looking

at the picture. So, by feeding this

information back into the AI, we teach

the machine about what it is like being

human, while at the same time, we gain

a unique insight into what being human

even means,” Spape said.

In a session with thirty participants,

the researchers formulated a setup

similar to Tinder, in which the

participants were shown a series of

images derived from a generative

adversarial neural network (GAN) that

used a dataset to create zillions and

zillions of different images that looked

like they could be of celebrities. These

images were artificially engineered from

real celebrity images. Instead of having

participants swipe right as Tinder users

normally would when faced with an

attractive image, researchers simply

used brain activity measuring caps to

track brain activity, which was then

analyzed by electroencephalography

(EEG). The EEG was connected to the


Artificial Intelligence

FEATURE

GAN: every time the participants’

brains demonstrated a positive

reaction towards a specific image, the

GAN generated more images that the

participant was likely to find attractive.

In the second half of the experiment,

the participants were invited back

for a double-blinded controlled

experiment and instructed to rate

their GAN-generated photos in terms

of attractiveness. The participants

found that around eighty percent of the

photos generated suited their personal

preferences, significantly far above

control conditions.

Interestingly enough, the participants

would not be explicitly rude about the

faces generated when asked about their

attractiveness, despite knowing they

were AI-generated images and not real

ones. Generally,

the negative

responses fell

into one of three

categories: blamed

their personal

preference for their

lack of attraction to

the face (clarifying

that they might not

find it attractive

but others might),

associated the

face with negative

personality traits

(for example, stating, “His smile… too

bossy”), or blamed the source material for

their lack of attraction. These interviews

were conducted after the big reveal,

ensuring its blind procedure.

Nevertheless, while the participants

downplayed their unattraction towards

certain images during the second half of

the experiment, they generally reacted

positively to the GBCI-generated images.

Overall trends showed a general preference

for blonde hair and youthful faces for

male participants. Female participants

often linked age with facial features. For

example, a lack of a beard was associated

with a youthful appearance and a lack of

hair was associated with age.

“The interview tells us that while

obviously they explain their attractiveness

decisions first as a pretty objective

process of checking against readily

identifiable [physical] features, like hair

color, age, and so on, they continue in


more psychological explanations of their

preference—‘This person looks kind.’

This ascribing of humanity continues

all the way to the extent that they even

expressed resistance in saying anything

rude to an image,” Spape said.

The ability of the GAN to recognize

implicit preferences within the human

brain demonstrates the advances

of computer technology. AI can

potentially model individual human

behavior, including latent mental

functions, meaning those that do not

require conscious thinking. In this way,

computer technology can potentially

decode the inner workings of the human

brain, diving deep into our deepest

thoughts and perceptions.

Spape hopes to move the study beyond

its current application to reveal insights

We teach the machine about what

it is like being human, while at the

same time, we gain a unique insight

into what being human even means.

into other core human behaviors, such

as implicit biases or stereotypes. Since

the computer has shown the capability

to “decode” attractiveness, a mental

process people themselves do not fully

understand, its potential to analyze

implicit biases and stereotypes—other

mental processes we do not explicitly

think about—is huge.

From the computer science perspective,

Ruotsalo strongly believes that the ability

of the computer to recognize human

perspectives can be used to add a touch

of creativity to technology.

“It’s very exciting to see that computers

can actually capture something much

more complex than a command. We can

make them understand something that

is subjectively important for people, and

allowing this generative loop takes this

[technology] towards something that

could support creativity, rather than just

transmitting a command,” Ruotsalo said.

However, there are some limitations to

the study that may not exactly replicate

results in real life. Ruotsalo recognizes

the limitations of using a database of

celebrities for generating the images.

“I think it has both pros and cons. The

training data is made up of supposedly

generally attractive-looking people,

which makes it more challenging to

personalize. . . . it's not representing

the overall population,” Ruotsalo said.

Additionally, the celebrity dataset

does not account for a diverse array of

ethnicities due to its inherent limitations.

Since the study focuses on the

intersection

between human

thinking and

c o m p u t e r

science, Spape

also recognizes

the limitations

of applying

computer-based

thinking to reallife

applications.

“As a psychologist,

it would be great

if we could say

that [what] we are

finding is actually a perfect match for

a mental model. We know that to some

extent we are finding something certainly

related to a mental 'picture,' but that

might also be some sort of local optimum.

Another question is, of course, whether

we can get further than just attractiveness,

and study also other aspects of social

perception as well,” Spape said.

Nevertheless, with the potential

to decipher other aspects of human

preference, the GBCI technology reveals

more about the human psyche than ever.

In the future, the technology could lead

to the advent of other new innovations,

including artificial intelligence to find

implicit biases behind behavior and

psychology. ■

Spape, M., Davis, K. M., Kangassalo, L. K., Ravaja, N., Sovijärvi-Spape, Z., & Ruotsalo, T. (2021).

Brain-computer interface for generating personally attractive images. IEEE Transactions on

Affective Computing, 1-13. https://doi.org/10.1109/taffc.2021.3059043


FEATURE

Medicine

GYNECOLOGY FOR GUYS:

MALE BIRTH CONTROL

HOW AN ANCIENT CHINESE HERB MAY BRING US

CLOSER TO CONTRACEPTIVE EQUITY

Oral birth control, commonly

referred to as “the pill,” is

prescribed to millions of women

in the United States as a convenient and

effective way to prevent pregnancy,

treat acne, regulate periods, and more.

While the pill in the 1950s marked

a triumph for women’s reproductive

rights, the history of birth control is

one deeply rooted in injustice. From

the propagation of eugenics ideology

to the mass sterilization of Puerto

Rican women during the Rio Piedras

clinical trials, the development of

oral contraception directly targeted

impoverished Black and Brown

communities in the United States.

Even today, the economic and

health-related burdens associated

with preventing pregnancy fall

predominantly on women. This has

long been due to the lack of birth

control options available to men. While

women have over ten birth control

options including barrier (condoms,

diaphragms, and sponges), hormonal

(pills, patches, shots, and rings), and

long acting, reversible contraceptive

methods (IUDs and implants), men only

have two: condoms and vasectomies.

After twenty years of studying sperm

formation, researchers at the Lundquist

Institute at Harbor-UCLA Medical Center

have recently discovered that triptonide,

a compound purified from the Chinese

herb Tripterygium wilfordii Hook F, can

demonstrate reversible contraceptive

abilities in men. With this finding, a

reversible non-hormonal male contraceptive

may be on the horizon, making equitable

reproductive health a possibility.

For over five decades, researchers

have tried to develop contraceptive pills

for men with no success. Previously, the

mainstream approach for developing

male contraceptives involved blocking

sperm production. The belief was that

if sperm counts were reduced to zero,

there would be no sperm available to

fertilize eggs and, therefore, pregnancy

would be prevented. The problem

with this approach, however, is that it

requires depletion of sperm precursor

cells, which is hard to achieve and tends

to cause significant side effects.

Wei Yan, principal investigator of

the study, explored a new, innovative

approach for developing male

contraceptives. Instead of depleting

all sperm cells, Yan sought to disable

sperm by causing deformation during

spermiogenesis, the maturation process

of spermatids (immature male germ

cells) into sperm. By disrupting the final

steps of sperm assembly, Yan theorized

that sperm would become incompetent,

or unable to fertilize eggs, due to their

malformation, while sperm count and

testis size would be largely preserved.

Towards this goal, the researchers

combed databases containing thousands

of drug candidates with documented

side effects in search of a compound with

sperm deforming effects. Tripterygium

wilfordii Hook F, sometimes called

thunder god vine, has long been used

in traditional Chinese medicine to

treat autoimmune and inflammatory

diseases like rheumatoid arthritis and

lupus. Ever since the first reported cases

of infertility in men after taking this

herbal medicine, researchers have spent

years isolating and purifying different

compounds of this herb in an effort

to identify which specific compound

caused deformed sperm. However, many

of these purified compounds caused

severe liver toxicity or had limited

reversibility of contraceptive ability. In

hopes of isolating a compound of the

herb that demonstrated reversibility

in male fertility without serious side

effects, the researchers persisted in

their testing and ultimately observed

that triptonide displayed the desired

contraceptive properties.

After administering triptonide at

different doses to adult male mice, the

researchers found that between three

and four weeks, daily oral consumption

of triptonide at a dose of 0.8mg/kg

body weight (BW) induced deformed

sperm with limited forward motility,

successfully causing infertility.

Repeating this experiment with

cynomolgus monkeys, the researchers

similarly observed that daily intake of

triptonide at 0.1mg/kg BW for five to

six weeks led to male infertility due

to disabled sperm. In both mice and

monkeys, the induced infertility was

found to be fully reversible, meaning

that fertility was regained between four

to six weeks after stopping consumption

of the contraceptive. This reversibility

in contraceptive effects is essential in

granting the consumer more flexibility

over his own fertility.

The testes of both mice and monkeys

maintained normal morphology without

any severe cell depletion, meaning

sperm counts remained relatively

normal during triptonide treatment. The


Medicine

FEATURE

BY ANGELICA LORENZO | ART BY NOORA SAID

difference between triptonide-treated

and control animals was that the former

displayed deformed sperm, particularly

a “head-bent-back” phenotype with

complete inability of forward motility.

To understand what this looks like,

picture sperm as a tadpole, containing

both a head and a tail. Spermatids, the

precursors to sperm, are round and

do not have a tail. In order to mature

into sperm, spermatids undergo an

elongation process in which the head

becomes compacted and the tail forms

through gradual elongation. This

coordinated process is controlled by the

gene SPEM1, which allows the tail and

head to grow proportionally.

Normally, SPEM1 interacts with a

protein called junction plakoglobin;

however, in the presence of triptonide,

this interaction is blocked due to

junction plakoglobin’s higher binding

affinity to triptonide. When SPEM1 and

junction plakoglobin are unable to bind,

the elongation process of spermatids

is disrupted. “The consequence [of

inhibiting the SPEM1 gene] is that you’re

going to have a head that is all bent back

and sometimes the tail actually starts

wrapping around the head,” Yan said.

Deformed sperm are unable to

fertilize eggs because of their inability

to swim vigorously to meet the egg

and because defective sperm tails are

not strong enough to penetrate the egg

during fertilization. With the inhibition

of SPEM1, spermiogenesis lacks a

checkpoint mechanism to eliminate

deformed spermatids. Importantly, this

missing “quality control” is advantageous

to birth control safety because normal

sperm counts are preserved.

Because two abundant compounds

of the Chinese herb—triptolide and

triptochloride—are known for causing

liver toxicity, many grant reviewers

rejected Yan’s applications because of the

herb’s notorious reputation.

“At a certain point, I wanted to give up

because [the project] just didn’t go anywhere

without funding,” Yan said. “I was lucky

enough to secure private funding.”

Now that triptonide has successfully

displayed reversible contraceptive effects

in both male mice and monkeys without

side effects, when can it be used by human

men? Before any clinical trials, the

Food and Drug Administration (FDA)

must approve the drug’s Investigational

New Drug (IND) status. Before that,

pharmacokinetics and toxicology

studies must be conducted to further

assess safety and metabolism of the drug

in the body. Ultimately, securing further

funding is the prerequisite to move this

project forward.

So why has it taken so long to

make progress in developing male

contraceptives? While funding poses a

challenge, Yan believes the underlying

reason is because of lack of success with

popular methodologies. As described

previously, the standard research

approach for inducing male infertility

has historically been sperm depletion.

Finding a chemical that can deplete all

sperm cells without causing adverse

effects has proven difficult.

“A popular joke in the field is that

male contraceptives have been five

years away for fifty years,” Yan said.

With the success of treating animals

with triptonide, Yan hopes that he can

find enough financial support to bring

triptonide drugs onto the market. Not

only will this achievement allow for

shared contraceptive responsibility

between men and women, but it will

also provide men with more autonomy

over their reproductive health. After all,

according to Yan, “to control your own

fertility is a basic human right.” ■

Chang, Z., Qin, W., Zheng, H., Schegg, K., Han, L., Liu, X., ... & Yan, W. (2021). Triptonide is a

reversible non-hormonal male contraceptive agent in mice and non-human primates.

Nature communications, 12(1), 1-14.



FEATURE

Ecology

MIGRATORY STRATEGIES

PAST, PRESENT, AND FUTURE BY MADISON HOUCK

ART BY ANMEI LITTLE

In the coldest depths of winter, many of us spend our

hours wishing we could move somewhere warmer.

Luckily for them, many species of birds have perfected

this process. Birds' seemingly intrinsic ability to navigate has

always left us with more questions than answers, especially

now as climate change threatens the migration routes and

survival of many avian species. To investigate the formation

of migratory patterns across thousands of years, and to

demystify the relationship between climate and migration,

a research team from the Chinese Academy of Sciences

collected migratory data to model the effects of rising global

temperatures on migratory strategies in years to come.

The peregrine falcons studied here typically live and

breed in the Arctic, but every September they embark

on a month-long journey to find solace (and warmth)

during the winter. These “wintering locations”

are mostly located in tropical or temperate areas.

In order to study current migration patterns of these

falcons, the team strapped satellite trackers to the backs

of forty-one peregrine falcons and sent them on their way,

monitoring their locations for an entire year. Birds that

were tracked for more than this one-year period

returned to the same migratory route year

after year, settling in the same


location each October.

Additionally, it was

determined that birds from the

same population migrated using

s i m i l a r pathways, but not all peregrine

falcons wound up in the same wintering

areas. This is referred to as “individual

migration”—different populations of

peregrine falcons have their own unique

migration strategies that depend on a variety

of factors. Such behavior offers valuable insight

into the influence of seemingly tiny changes in

climate on overall migration behavior.

Scott Yanco, an incoming postdoctoral researcher

at the Max Planck Yale Center for Biodiversity,

Movement, and Global Change, praised the methods that

the research team used, citing that the transmitters had a

spatial error of only a few meters. “We really know where that

bird was,” he said, laughing. “We’re in a golden age for that.”

“One of the big holy grails, at least in my opinion for

migration, is: why does it happen? There's all these different

adaptations that organisms show to seasonality, and migration

is just one of them,” Yanco said.

Towards this question, the team also studied the intrinsic,

genetic component of migration. After studying a wide variety

of falcon populations with observably different migration

patterns (long versus short migratory paths), it was suggested


Ecology

FEATURE

that the ADCY8 gene had a large effect in

directing migration of peregrine falcons.

An epigenetic modification actually

results in over-expression of the ADCY8

gene in falcons that must travel long

distances, leading the research team to

believe that the gene is directly related

to long-term memory. This indicates

that migration is a combination of

intrinsic ability to remember pathways

and learned behavior from other falcons

or previous experience. This is also

supported by the fact that the level of

expression of the ADCY8 gene correlates

with the length of the migratory journey.

Yanco thinks this kind of research

touches on a question that has been everpresent

in the field of migration. “What

they've been able to do here,” he said,

“that is relatively new and I think very

few authors are working on, is the sort of

ultimate drivers. Why do it? How does it

happen? How does something like this

emerge in the first place in deep

evolutionary time? How is it

maintained?” These questions

will propel the field forward to

looking at the underlying why in

migratory patterns.

The research team then set

out to determine the history

of migration and how it was

impacted by large scale climate

changes in history, such as the melting

of the ice caps. By modelling historical

migration paths, they were able to

determine that as the ice caps melted,

northern falcon populations decreased

due to disruptions to their breeding

grounds. Breeding grounds shifted north

in order to maintain a similar temperature

environment for the falcons, lengthening

the falcons’ migratory path. As discussed

above, the length that a falcon can

travel is at least partially genetically

determined, meaning that only birds that

were genetically predisposed to remember

and travel long distances were likely to

survive long journeys. This particularly

brutal bout of natural selection resulted

in a dramatic decrease in the population

of peregrine falcons.

In addition to impacting the duration

of the migratory journey, changing

temperatures and melting glaciers also

impacted the directional orientation

of migration routes. During the last

Ice Age, or the Last Glacial Maximum,

there were many more accessible

wintering locations to the west, whereas

now, there are a relatively equal number

of western and eastern locations.

Both of these changes demonstrate

that global climate can have a marked

impact on migratory routes and relative

survival of the peregrine falcon species,

and likely other species of Arctic birds as

well. The findings offer a grave perspective

on the impact of current rising global

temperatures on Arctic avian populations.

Having studied how climate change has

impacted migration in the past, as well

as migratory routes in the present, the

research team then directed their attention

towards the future. To study how presentday

climate change would impact future

survival of the peregrine falcon species,

“Some groups of peregrine falcons

”

could lose between ninety and one

hundred percent of all suitable

breeding grounds.

they used ecological niche modelling

simulations to predict how rising global

temperatures would affect potential

breeding grounds and wintering areas.

The results were striking. Some

groups of peregrine falcons could lose

between ninety and one hundred percent

of all suitable breeding grounds, a

development that would be devastating

to those populations. As a result,

populations with short migratory routes

would see a decrease in migration

distance, eventually reaching the point

where they wouldn’t migrate at all,

while populations with long migratory

journeys would see further increases in

distance. Longer migration routes are

more closely correlated with mortality,

so lengthening an already long and

harrowing journey could devastate the

population size substantially.

IMAGE COURTESY OF WBUR

Melting ice caps in the Arctic reflect rising

temperatures and changes to Arctic climates that

threaten the breeding grounds and migration

routes of peregrine falcons.

According to data from the team, these

shifts have already begun. Retroactive

analysis of peregrine populations

found that population numbers have

been declining for the past twenty-five

generations: the future doesn't look

bright for peregrines.

What does this mean for the rest of us?

While some might hesitate to

understand how a peregrine falcon

can represent the world, this work

has done nothing if not convey how

interconnected our planet is. The

same climate changes that impact

these falcons will undoubtedly

have similarly intricate impacts

on our ways of life, especially if

no steps are taken to slow rising

temperatures in the coming years.

The Chinese team’s study is unique in

that it focused heavily on one species,

using a wide variety of tools and research

methods to create a complete and almost

definitive picture of the migration

patterns of peregrine falcons.

“One of the cool things in this study

was that they integrated approaches

that are often quite siloed. And I think

that this makes a compelling case

for putting together teams that can

do that stuff—that you're looking at

things behaviorally, environmentally,

ecologically, and [with] molecular tools,”

Yanco said. “I mean, I think there’s a

broad trend in science, that it’s becoming

more interdisciplinary and [with] larger

teams. As we reach the limits of what we

can infer with any given tool, it becomes

important to start expanding out.” ■

Gu, Z., Pan, S., Lin, Z., Hu, L., Dai, X., Chang, J., ... & Zhan, X. (2021). Climate-driven flyway changes and memory-based long-distance

migration. Nature, 591(7849), 259-264.



PHYLLIS MUGADZA

(BS/MPH ’22)

BY EAMON GOUCHER ART BY ELLIE GABRIEL

UNDERGRADUATE PROFILE

In a normal year, you can find Phyllis Mugadza (’22 BS/

MPH) hanging out in the Silliman courtyard, giving tours

of Yale’s campus, or working as a recruitment coordinator

in the admissions office. In between classes and work,

Mugadza, a mechanical engineering major, spends her free

time innovating the world around her.

This past winter, Mugadza was selected as one of the winners of the

2020 Reimagine Challenge, a scholarship competition that aims to

identify innovative solutions that will help spark global movements

and build back from COVID-19. For her proposal, Mugadza

focused on the growing waste mismanagement crisis in several

developing nations. Despite the serious public health problems

they pose, waste sites have become unique spaces of creation in

which grassroots innovators repurpose discarded materials into art

and commodities. Mugadza, inspired by the creative superpower

of these creators, proposed a novel method of addressing the waste

mismanagement crisis: opening makerspaces to support grassroots

creators, bolster local economies, and repurpose waste.

Mugadza’s passion for innovation first blossomed out of a desire

to help her home community in Harare, Zimbabwe. “The biggest

challenge I found was that a lot of women around me were missing

school—my friends would miss work when they were on their

period because of dysmenorrhea, or menstrual pains,” she said. The

inaccessibility of medicine, sanitary products, hygienic facilities,

and education on menstruation created ubiquitous barriers to

everyday life. “When I committed to Yale, I wanted to commit my

entire engineering journey to finding a solution for this problem,”

she said. Over the past four years, Mugadza has collaborated

with OB-GYNs at the medical school, conducted surveys with

menstruators of all identities, and iteratively designed a device that

can effectively collect menstrual blood and treat dysmenorrhea.

Listening to Mugadza feels liberating; her passion is palpable.

Over the course of our conversation, I realized that Mugadza’s

unique perspective comes from a belief in the potentiality of objects

and people to build a happier, safer, and more equitable world. For

her Reimagine Challenge proposal, Mugadza emphasized breaking

out of a functional fixedness mindset—using everyday materials

in new and exciting ways. Mugadza is inspired by the work of

architects Kevin Kimwelle and Ashis Paul, who have built plastic

bottles in their designs as storage hooks and as naturally cooling

air filters. Mugadza wanted to center this kind of ingenuity in her

project proposal. She believes that in order to solve this problem,

we must empower local creators: “They possess a gift and a talent

that the world needs right now,” Mugadza said.

As she described the process of designing a menstrual device, I

started to understand Mugadza’s experience in reimagining a better

world. “I would say that a lot of my inspiration and motivation come

from studying engineering at a university that is rooted in the liberal

arts,” she said. Especially at first, Mugadza leaned heavily on Tsai

City and her mentors for both guidance and support. She points to

Alyssa Siefert, Christina Mainero, and Anjelica Gonzalez as some

of the people who have helped her get to this place. “Mentorship

has been extremely important, especially being a woman of color

in engineering at Yale and all that comes with that,” she said. “My

mentors have really uplifted me, connected me to resources, have

pushed me to take up space, and always push me constantly to

achieve.” Still, Mugadza is very transparent about her experiences

being a woman of color in engineering and entrepreneurship: “I’ve

had to put in a lot of extra work to make my voice heard in a lot

of spaces. I felt like I was constantly being sheltered and limited by

what I could achieve,” she said. In times like these, Mugadza turns

to her mentors—particularly her female mentors of color—to help

her get back to doing what she loves: building a better world.

Mugadza will graduate from Yale College in May, before

moving to the School of Public Health full-time to complete

her MPH. She hopes to launch her menstrual device startup

Sprxng by the end of the year and plans to resume work on

her makerspace project within five years. I

walked away from our conversation

feeling inspired and excited

about the future. We

often tend to

feel like very

small cogs

in a very big

machine—

everything

we do is a

drop in the

bucket. But

Mugadza has

demonstrated

the power that

each person

has in creating

a happier, safer,

and more equitable

world. ■


DR. C. BRANDON OGBUNU

(PHD ’10)

BY ANNA CALAME ART BY ELLIE GABRIEL

ALUMNI PROFILE

Ten minutes into my conversation with Dr. C. Brandon

Ogbunu (PhD ’10), I knew that no 750-word profile could

fully do him justice. Throughout his life, Ogbunu has

consistently pushed boundaries and rejected dichotomy, making

for an impressive career that resists abridgement. Ogbunu is

a scientist, yes, but he is also a prolific writer, storyteller, and

educator. His nontraditional, interdisciplinary path has led him

to the Ecology & Evolutionary Biology Department at Yale,

where he is an assistant professor and the principal investigator

for the Ogbunu Lab for Genetics, Ecology, Evolution, and

Quantitative Science (GEEQs) research.

Despite being a self-described “late bloomer” academically,

Ogbunu emphasizes that he has always harbored a deep love

of learning. He credits his mother, a teacher, with imparting to

him this proclivity for scholarship, which blossomed during his

undergraduate years at Howard University. There, Ogbunu studied

chemistry, explored the intersections between various scientific

disciplines, and developed an interest in disease. After graduating

from Howard in 2002, Ogbunu studied malaria in Kenya on a

Fulbright scholarship, an experience that confirmed his preference

for research over clinical practice. “It was when I got to Kenya that

I said, if I can be doing this kind of work as a grown-up, this is

the career that I want: the producing and engaging of scholarship,”

Ogbunu said. “Science is a type of scholarship; it’s a manner through

which a person creates knowledge and offers it to the world.”

Upon returning to the US, Ogbunu

followed his curiosity to Yale,

where he worked in Paul Turner’s

virology lab. He completed

his PhD in microbiology

in 2010 and, subsequently,

a postdoctoral fellowship

at Harvard. Ogbunu spent

two years working at Brown

University before returning

to Yale in the fall of 2020, this

time as a faculty member.

Ogbunu, a computational

biologist trained in chemistry,

mathematics, genetics, evolution,

and microbiology, approaches research

in a way that reflects the diversity

of his interests and abilities. His

GEEQs lab conducts “remix

science,” drawing on concepts from various scientific fields to gain

insight into disease. Ogbunu considers research questions on two

levels: the molecular scale, comprising technical knowledge of

genetics and biology, and the population scale, involving modeling

and data analysis. Together, they have brought him great success and

an enduring love for his work. “[The multidisciplinary approach] is

just more fun—I can talk to more people, I can engage more people,”

Ogbunu said. “On one end, these two lenses allow me to comment

on and think about very practical things. On the other, they let me

ask broad questions about society or evolution or ecology.”

Ogbunu is a staunch believer in the importance of collaboration.

Throughout our discussion, Ogbunu was quick to credit the

positive influences that others, particularly his mother, his college

friends, and Turner, have had on his life and career. When asked

how his passion for community informs his approach to teaching,

Ogbunu described the ability to craft an engaging and supportive

lab environment as an “incredibly exciting” aspect of being a

principal investigator. “I do a self-care symposium in my lab,

where every year you have to present on the ways you’re going to

take care of yourself, and answer questions,” Ogbunu said. “I can

work my value system into the ways my lab interacts.”

Consistent with his lifelong love of learning and creating

scholarship, Ogbunu is also an impressive communicator,

having written numerous blog posts, contributed to WIRED,

and appeared on podcasts. “I’ve always been connected to

writing—I’ve read comics all my life. Writing and art and being

creative have always been a part of my identity,” he said. Rather

than seeing his creative pursuits as separate from his dedication

to science, Ogbunu considers his writing, his scientific process,

and his teaching to be complementary. Through his writing,

Ogbunu skillfully explores questions at the intersection of

science and society: the limitations of analogizing infectious

disease and white nationalism, the potential of network science

to make sense of our increasingly interconnected world, and

the insidiousness of scientific racism and the legacy of James

Watson. Moreover, he presents his thoughts on these complex

and technical topics in ways accessible to the average reader.

Ogbunu’s success serves as a reassuring reminder to my

fellow students, anxious over seemingly binary decisions

between disciplines and unsure of how to appropriately

navigate the professional world. Prioritizing a dedication to

one’s values—in Ogbunu’s case: community, scholarship, and

creativity—over an adherence to previously-trodden paths is

not only possible, but highly rewarding. ■



VIVEK MURTHY’S TOGETHER: THE HEALING POWER OF

HUMAN CONNECTION IN A SOMETIMES LONELY WORLD

BY HANNAH HUANG

Whether it be walking into a room of strangers or standing alone at recess,

everyone has felt lonely at some point. Vivek Murthy (SOM ’03), the

nineteenth and twenty-first Surgeon General of the US, built his platform

on combating loneliness after realizing how insidious its long-term effects are. In his

book Together: The Healing Power of Human Connection in a Sometimes Lonely World,

Murthy explains that because loneliness is the root cause of many societal problems,

combating loneliness ultimately bolsters our collective health.

Murthy’s childhood role models were his parents. Physicians themselves, they built

relationships with their patients by taking time to listen to their needs. When Murthy

began his first stint as Surgeon General, he took his parents’ example to heart and

embarked on a listening tour across America to identify the most pressing health

issues Americans were facing. Between those listed—addiction, violence, anxiety, and

depression—there was a common connector. “To be at home is to share a sense of

common ground, common interests, pursuits, and values with others who truly care

about you. In community after community, I met lonely people who felt homeless

even though they had a roof over their heads,” Murthy said.

The link between loneliness and physical health, though surprising when first

discovered, is nonetheless an established one. Psychologist Julianne Holt-Lunstad

found that loneliness is a stronger risk factor for reduced life span than obesity,

alcoholism, and lack of exercise. In fact, lack of social connection is as detrimental

to one’s health as smoking fifteen cigarettes a day. “If neglected, loneliness can

have long-term health implications, yet it is not a state that can be fixed with a pill

or a procedure. It is a human condition that reminds us of our need for the love,

compassion, and companionship of fellow human beings,” Murthy said.

Given the current state of social distancing and mandated isolation, it’s likely

that loneliness is more prevalent than ever. However, Murthy insists that physical

solitude doesn’t necessarily translate to loneliness. “Loneliness is the subjective

feeling that you’re lacking the social connections you need. Solitude, by contrast,

is a state of peaceful aloneness or voluntary isolation. It is an opportunity for selfreflection

and a chance to connect with ourselves without distraction,” Murthy said.

Murthy believes that even in the current pandemic, we can find ways to

combat loneliness while finding peace in solitude. He lays out four strategies: 1)

spending time each day with those you love, even if it’s fifteen minutes on a video

call; 2) giving other people your full, undivided attention when conversing; 3)

performing acts of service to be reminded of how we can support each other; and

4) embracing solitude through nature, meditation, and art.

“Developing comfort with solitude is an essential part of strengthening our

connection to ourselves, and by extension, enabling our connection with others.

Solitude, paradoxically, protects against loneliness,” Murthy said. Even in the despair

of this past year, there may be a hidden blessing if one ascribes to Murthy’s teachings. ■

IMAGE COURTESY OF THE ACCREDITATION COUNCIL FOR

GRADUATE MEDICAL EDUCATION

Dr. Vivek Murthy participates in a fireside chat at the 2019 Annual

Educational Conference.

SCIENCE IN TH



THE NOCTURNISTS

BY ANN-MARIE ABUNYEWA

IMAGE COURTESY OF

CANVA

Medical professionals “pull back the curtain on medicine,” as host Emily

Silverman describes her show.

Just as Charon ferried souls post-death across the River Styx to receive their

fate, death too propelled Jenny Tiskus into her journey with medicine.

In “The River Styx,” an appropriately named episode of the podcast The

Nocturnists, Tiskus explores gallows humor and how physicians process death.

She reflects on the deaths of her father and grandmother and her initial hesitance

to go into medicine. Her wandering back between a life with and without

medicine feels reminiscent of the wandering souls of the Greek Underworld

river, who anticipate the moment when their afterlife fates become clear.

The Nocturnists is a podcast in which healthcare workers share their experiences

in the field. Integral to each episode is the art of storytelling. The anecdotes that

each guest shares are raw: listeners feel as though they have a special insight into

healthcare without having to enter the hospital or clinic themselves. They learn

about healthcare professionals’ joys and vulnerabilities while working in the field.

March 2020 marked the beginning of The Nocturnists’ “Stories from a

Pandemic” series. This season is particularly moving; though our one-year

anniversary since the beginning of the COVID-19 pandemic has passed, all the

initial emotions and reactions are still incredibly tangible. The hope, exhaustion,

and cynicism that listeners have in common with storytellers grounds the

healthcare workers as people like us, rather than sacrificial heroes the media

glorifies. “It’s not bad yet. It's a whole lot of unknown,” recounts a trauma nurse

as she marvels at her colleagues’ smiles despite their surging anxious emotions.

“[The hospital] sent me home early today because I'm getting too much

overtime. Apparently being willing to make sure that our patients get their stuff

is too expensive,” reports a Durable Medical Equipment truck driver.

This season, the producers have expanded the podcast to make it a nationwide,

collaborative effort. They created an interactive map where each destination

features a story from a healthcare worker into which listeners can tune. Usually,

the podcast uses music by composer Yosef Munro to open and close episodes.

However, the only music featured this season is that provided by the diarists. At

the end of “Stories from a Pandemic: New World,” an internal medicine resident

details that she picked up music again because it gives her the comfort that

uncertainty has often taken away; she closes out the episode playing Dvorak’s New

World Symphony on her violin. By incorporating these collaborative components,

the producers have elevated this season’s storytelling power, authenticity, and

connectedness—an important mission now that we have been so apart.

Looking back on her journey into medicine, Tiskus worries about the “emotional

desiccation” that could ensue as her profession exposes her to more death. To combat

this, she says it’s important to discuss how to stay in touch with her humanity when

gallows humor seems to strip it away. Storytelling through The Nocturnists is how she

can more fully emphasize the gravity of the deaths that shaped her path to medicine. ■

E SPOTLIGHT



COUNTERPOINT

NOT-SO-IDENTICAL

TWINS

BY EVA SYTH

The classic scientific debate on “nature vs. nurture” asks:

to what extent do genetics shape our characteristics,

and to what extent do our environments shape our

characteristics? In pursuit of the answer, scientists historically

studied identical twins, or monozygotic twins, who were widely

believed to share the same DNA. To isolate differences associated

with nature as opposed to nurture, these studies assumed that

any differences in identical twins must have been due to the

environment, as their genetic material would be the same.

However, new research from Hakon Jonsson and Erna

Magnusdottir, as well as collaborators at deCODE genetics, the

University of Iceland, and Reykjavik University, suggests otherwise.

The team recently found that identical twins on average differ by

5.2 mutations from early in the life cycle. The study, which involved

the genetic sequencing of almost fifty thousand people, further

showed that, in fifteen percent of identical twins, one of the twins

has a substantial number of mutations that the other does not have.

Beyond quantifying the average mutation differences

between monozygotic twins, this study also looked into when

the mutations occurred during development. Jonsson and the

research team cleverly used information on early development,

coupled with genetic sequencing of identical twins along

with their parents, spouses, and children, to draw inferences

surrounding the timing of mutations during development.

So, how exactly can researchers use the genetic sequences

of these close contacts to decipher when mutations occurred?

The answer relies on the very beginnings of the human life

cycle. When an egg cell is fertilized, it becomes a single-celled

zygote, composed of genetic material from both parents. Over

time, the zygote divides and embeds itself into the uterine

lining to form the blastocyst. After several weeks, some of the

cells are designated to be germ cells, or sex cells. Sex cells are

involved in passing genetic material on to offspring.

Twinning occurs when the single mass of developing cells

splits into two identical masses, which eventually become the

two twins. This process generally occurs early in development,

much before the designation of germ cells.

The researchers used the development process coupled with

genetic information from relatives of identical twins to determine

at what point mutations occurred in development. For example,

IMAGE COURTESY OF PIXABAY

the researchers identified mutations in an identical twin and

their offspring, but not in the twin’s spouse or twin counterpart.

Of these mutations, the researchers then found that some were

also present in somatic body cells of the twin. From the life cycle,

the researchers could extrapolate that the mutation occurred

after twinning, because the twin’s monozygotic counterpart

didn’t have the mutation. Additionally, because the mutation

was present in both somatic cells and germ cells, investigators

inferred that the mutation likely occurred before the germ line

cells were designated. If this wasn’t the case, the mutation would

have been found in either somatic cells or germ cells, not both.

The researchers used similar logic to identify at what point in

development a variety of mutations likely occurred.

In addition to identical twins, the researchers also investigated

a family with identical triplets in order to learn more about

genetic variation. Specifically, this case study proved crucial

in exploring cell allocation. Cell allocation is concerned with

the designation of different cell types. For example, twinning

may occur when a group of cells is designated and begins

developing independently of existing cells. In the case of the

triplets, researchers found that two of the triplets shared more

mutations with each other than the third. The study pointed to

cell lineage as a potential explanation: two of the triplets were

likely “descended” from the same cell whereas the third triplet

came from another set of cells that was allocated separately.

So where does this leave identical twin studies, which assume

that these mutations are insignificant compared to environmental

factors? Jonsson and the research team caution that the effects of

these mutations have likely been underestimated when it comes

to the development of certain diseases. However, even if nature

vs. nurture identical twin studies are eventually retired from the

field, studies involving twins still have their place: further work

can be done with identical twin genetics to better understand

early stages of human development. ■

Jonsson, H., Magnusdottir, E., Eggertsson, H.P. et al. (2021). Differences

between germline genomes of monozygotic twins. Nat Genet, 53,

27–34. https://doi.org/10.1038/s41588-020-00755-1


IMAGE COURTESY OF CARL ZIMMER

INTO THE

NEWSROOM

A CONVERSATION WITH

CARL ZIMMER

By Sophia Li

Carl Zimmer’s award-winning science journalism regularly

features in the New York Times. A Yale alum (’87) and

professor adjunct, Zimmer has also authored fourteen

books. His most recent, Life’s Edge: The Search For What It Means

To Be Alive, was published in March of this year.

This is an abridged version of YSM’s recent conversation with

Zimmer. For a full version, visit https://www.yalescientific.org/.

How did you get into covering for the New York Times?

I really loved to write and graduated from Yale as an English major. I

worked at Discover for ten years before deciding I just wanted to work

on my own projects and started writing for National Geographic and

Wired. In 2004, I pitched the idea of a science column to the NYT. The

editor who read my pitch was happy to talk about ideas and we started

off with a story on why leaves change color in the fall. And after that, I

started contributing stories to them until it became a weekly column.

How do you make scientific information understandable to a

broader audience?

When I start working on a story, I will get familiar with the research

that was important to make the new discoveries possible. Then I

just have long conversations. I’ll talk to scientists about their work.

I might talk to outside scientists to get an expert opinion. If it’s the

kind of research that affects people’s lives, I will talk to those people.

When writing, I always remind myself that I have spent several

days or weeks immersed in this subject, whereas my readers are

coming to it completely fresh. You have to tell a story that’s clear

and compelling enough that people who aren’t experts will want

to read and understand it.

You recently published your book, Life’s Edge. Where did the

idea for it come from?

A lot of people, even when they’re kids, wonder, “Well, what is

life exactly, and what does it mean that we’re alive?” If you ask your

parents you might not get a satisfying answer, and it turns out if

you ask scientists you might also not be satisfied, because everyone

seems to have a different definition of it. I talked with researchers


and philosophers, spending time to look at particularly weird and

amazing forms of life, whether it’s hibernating bats or slime mold

or just a maple tree. I start the book in the familiar heartland of

life, thinking about things no one would really argue are alive (like

ourselves) and then move out to the borderlands where it suddenly

gets much harder to decide whether things are alive or not.

You write, “All life gives way to half-life and then to no life at

all.” Through your investigation, do you have a different way of

characterizing life?

Something like a virus shows you how shaky the whole edifice of the

definition of life is. Definitions, as we think of them, are kind of arbitrary

hallmarks. You don’t really get at something fundamental about nature.

We can have some sort of rough and ready definition, but in Life’s Edge, I

compare it to asking an alchemist in the 1500s to define water.

They would probably say: It’s wet, it’s transparent, it’s liquid,

and if I make it cold it gets hard. But then you say: Then, the stuff

it becomes, is that water too? Then they would say: No, that’s ice,

because water as I just told you is liquid.

So, it’s kind of a meaningless exercise to ask an alchemist to

define water. What you really want is a theory of chemistry. You

can say: According to your theory you call that stuff water. What’s in

it are these molecules, and I can tell you what molecules are, and I

can tell you how this particular substance has molecules that contain

oxygen and hydrogen. It’s still water when it freezes because the

molecules just arrange in different shapes. So suddenly I’ve told you

something deep and profound about water because I have a theory

of it. However, we don’t have a theory of life that everyone agrees

on yet.

Do you have advice for Yalies who want to engage with scientific

writing?

It takes a lot of practice, so nobody should expect to do a

spectacular job their first time out. It’s a big challenge to learn

about complicated things and write about them in an exciting and

comprehensible way that’s as close to the truth as you can make it.

Try to write it the way you actually talk. Tell us a good story about

science and we’ll want to read it! ■


Interested in getting involved with

Yale Scientific

ale_SC_ENG_half Winter Issue_2020.qxp_8 2/26/20 10:08 AM Page 1

for writing, production, web,

business, or outreach?

learn more at

yalescientific.org/get-involved

YSEA’s 2021 Awardees for

Outstanding Academic Achievement

YSEA’s 2021 Awardees for Outstanding Academic Achievement

Your achievements inspire all of us in the Yale STEM community.

Your achievements inspire all of us in the Yale STEM community

YSEA Award for Meritorious Class of 2021 Service to Yale University:

Amer Al-Hiyasat

Claire Lamarre

Joseph Cerro, Yale MB&B ’89, Technologist & Life Sciences Consultant and

Molecular Biophysics and Biochemistry / Physics Engineering Sciences (Chemical)

Elie Track, Yale PhD Physics '88, CEO of nVizix LLC

Joe and Elie are receiving Justin Cheong this year's award for their decades of commitment Sally Ma to the Yale-alumni STEM

connection. By managing Molecular, the Cellular, organization and Developmental and solidifying Biology our partnership Computer with Science Yale administration, they

have jointly established and maintained the pre-eminence of our centenarian institution.

Athena Flint

Anna Sun

Joesph Cerro

Elie Track

Chemistry (Int.)

Molecular, Cellular, and

Developmental Biology (Int.)

Class of 2022

YSEA Award for Advancement of Basic

YSEA Award for Distinguished Service to

Franklin Bertellotti and Applied Science: Matt King

Industry, Commerce or Education: Ecology and Evolutionary Biology Gary Chanan, Yale Mathematics Physics (Int.) / Mathematics and Physics (Int.) '70,

Eileen Pollack, Yale Physics '78, Jocelyn Chau

Professor Emeritus Steven of Physics Ma & Astronomy,

Professor, Writer

Molecular Biophysics and Biochemistry

University of California, Mathematics Irvine

Eileen is receiving this award for raising our Avi Cohen

Gary is a pioneer and Joy innovator Ma in telescope optics who

nation's consciousness about the continued Molecular, Cellular, and Developmental Biology

is receiving this year's Psychology award for / Ecology his fundamental and Evolutionary and Biology

under-representation of women and minorities Alexandra Galls

transformative contributions to the design and operation

Eileen Pollack

in science, and for tirelessly advocating Chemistry

Fiona O’Brien

Gary Chanan of segmented mirror telescopes, particularly the Keck

solutions across spheres of society.

Environmental Engineering

Rohit Giridharan

telescopes in Hawaii.

Electrical Engineering / Computer Science

Faiaz Rahman

Thank you for continuing Yale's rich tradition in STEM.

Eamon Awards Goucher shall be presented at the YSEA Annual Computer Dinner, Science Friday, April 17th 2020

For more information visit: ysea.org

Molecular Biophysics and Biochemistry

Graham Hardcastle

Computer Science / Economics

Alden Tan Ming Yang

Computer Science and Economics

YSM Issue 94.2

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