YSM Issue 95.3

Yale Scientific 

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

OCTOBER 2022 

VOL. 95 NO. 3 • $6.99 

14 

USING FIREFLIES TO 

COUNT HIV REPLICATION 

PERSONAL MATTERS 

12 

ON ABORTION 

THE WORLD 

16 

IN PROTEINS 

TURNING THE KNOTS 

19 

IN RESONATORS 

HOW TO GROW 

22 

A HEART

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TABLE OF CONTENTS 

VOL. 95 ISSUE NO. 3 

More articles online at www.yalescientific.org 

& https://medium.com/the-scope-yale-scientific-magazines-online-blog 

COVER 

14 

A R T 

I C L E 

Using Fireflies to Count HIV Replication 

Connie Tian 

The red queen hypothesis states that a species must constantly adapt and evolve for survival, 

because competing organisms are also evolving. To combat the evolving human immunodeficiency 

virus, we must continue to develop new retroviral drugs to treat affected individuals. Firefly 

bioluminescence could be key to developing new HIV treatments. 

12 Personal Matters on Abortion 

Van Anh Tran 

Sharing personal stories about abortion has been a powerful advocacy tool in the past to 

destigmatize abortions and to help others not feel alone in their experience. But a Yale study has 

found that the direct effects of storytelling on stigma may not be as clearcut. 

16 The World in Proteins 

Krishna Dasari 

Biologists have had to settle for proxy measures of cellular protein levels for decades. Now, an 

unexpected collaboration between an evolutionary biologist and a protein biologist has paved the 

way to study biodiversity and evolution at the level of the proteins themselves. 

19 Turning the Knots in Resonators 

Yusuf Rasheed 

Our world and beyond is filled with oscillators—piano strings, air particles, and colliding 

comets—and thus, understanding how they resonate is critical. The Harris and Read Labs 

at Yale recently discovered how topological structures called knots and braids are essential 

to oscillators. This opens the door to improving any system that has them, including 

computers, radios, and watches. 

22 How to Grow a Heart 

Catherine Zheng 

Engineered heart tissues grown from stem cells are often used in cardiac research and studies to 

model a mature human heart. Researchers from Professor Campbell’s research group at Yale have 

developed a new protocol that significantly reduces the time required to produce these mature 

heart tissues. 

www.yalescientific.org 

October 2022 Yale Scientific Magazine 3

A TRUE LOVE STORY: 

MOSQUITOES X US 

& 

THE NOT SO FOREVER CHEMICALS 

By Matthew Zoerb 

In 2018, Robert Bilott filed a lawsuit against three major chemical 

companies, 3M, DuPont, and Chemours, on behalf of every 

American exposed to per- and poly-fluoroalkyl substances 

(PFAS). PFAS are used in many water-resistant products ranging 

from waterproof jackets to non-stick pans. Since 1951, hundreds of 

thousands of tons of waste containing perfluorooctanoic acid (PFOA), 

a specific type of PFAS, have been dumped into the Ohio River and 

spread throughout the global biosphere. The ongoing litigation 

alleges that these companies have spread PFAS into the bloodstreams 

of ninety-nine percent of Americans while withholding information 

about their harmful side effects. Unfortunately, PFASs are resistant to 

degradation, and due to their long-lasting environmental presence, 

they are known as “forever chemicals.” 

Traditional methods to break apart PFAS involve pressurized 

incineration at one-thousand degrees Celsius. However, these 

techniques are costly and can spread the toxic compound into the 

atmosphere. A team at Northwestern University and UCLA recently 

discovered a new method to decompose PFAS. The researchers 

noticed an irregularity among the chain of tightly-bound atom 

clusters: a hydroxyl group or a chemical group composed of 

oxygen bonded to a hydrogen atom. This group could be broken 

off when mixing PFAS with two common solvents: DMSO and 

sodium hydroxide. By targeting the weakest bond and sequentially 

disassembling the PFAS at only one hundred degrees Celsius, the 

study suggests it is possible to convert PFAS into environmentally 

harmless products efficiently. This technique has limitations 

since bulk quantities of DMSO are prohibitively expensive for 

widespread use. Still, this result suggests that pollution from PFAS 

may not truly be around “forever.”■ 

By Lea Papa 

Mosquitoes are perhaps most well-known for causing 725,000 

human deaths annually and being extreme nuisances. The 

blood-suckers appear and are attracted to unique human 

odors. They then pierce human blood vessels and feed. 

The solution seems simple: to find a way to disable the 

mosquitoes’ sense of smell. However, according to a recent 

Rockefeller and Boston University study on the mosquito 

olfactory system, it may not be so straightforward. When 

researchers deleted chemoreceptors—channels on the 

mosquitoes’ cells stimulated by human odors—from the 

mosquito genome, they found that the mosquitoes were still 

attracted to humans. 

Typically, an animal’s olfactory neurons allow it to smell and 

express one type of chemoreceptor that detects one odor. In the 

mosquitoes’ case, researchers found that the antenna receptors 

detecting the human odor 1-octen-3-ol, a chemical in breath and 

sweat, are also stimulated by amines found on human skin and 

sweat. The expression of multiple chemoreceptor genes in olfactory 

neurons provides them with a fail-safe for finding human blood, 

even when their human-smelling sensors are blocked. 

For this reason, simply removing or blocking olfactory 

receptors from the mosquito genome will do little to prevent 

them from detecting humans. Still, this finding may be a step 

toward finally breaking free from the age-old relationship 

between humans and mosquitoes.■ 

4 Yale Scientific Magazine October 2022 www.yalescientific.org

The Editor-in-Chief Speaks 

THE SCIENCE AND 

TECHNOLOGY OF HUMANITY 

Science may present itself as rigid and automated—it is easy to get lost in objective 

formulas, theorems, and conclusions. However, this issue of the Yale Scientific 

Magazine highlights that science is, at its core, a human endeavor done by 

humans and for humans. Behind each formula, theorem, and conclusion is a person 

and a story. We are honored to tell a few of these stories from Yale and beyond. 

Our cover article highlights research from the Yale School of Medicine that used 

fluorescence technology in an HIV pathway for the discovery of small molecule 

treatments for the disease, which affects over thirty-eight million people (pg. 

14). Our other stories range in scale. One study investigated the effect of sharing 

personal abortion experiences on stigma and advocacy (pg. 12). Another studied 

the connection between proteins and biodiversity, paving the way to understanding 

our evolutionary history in a novel way (pg. 16). At the cellular level, research 

on stem-cell maturation works to model mature human heart tissue, making 

strides in the fight against cardiac diseases (pg. 22). And in physics, research on 

the mathematic fundamentals of resonators has implications for many systems 

around us, from watches to computers. This project highlights the teamwork and 

human communication required for successful science (pg. 19). 

In our own backyard, the Yale community sees science interacting with 

humanity from various angles, highlighted by this issue’s profiles. At just twenty 

years old, Yale College sophomore Shervin Dehmoubed co-founded and runs 

EcoPackables, a company providing sustainable packaging—an example of 

science harnessed for social good (pg. 34). In Yale’s Chemistry department, 

third-year graduate student Tyler Myers makes it a priority to inspire interest in 

organic chemistry by putting students first (pg. 35). 

While the study of science will inevitably be filled with the objectives, humans 

bring subjectivity to the equation, the good and the bad. However, the competition, 

greed, and dishonesty often seen in scientific research and applications are 

overshadowed by empathy, passion, and an ambition to leave the world better 

than it was. Science and technology cannot be separated from humanity. For our 

aspiring scientists, we hope you carry these human values throughout your career 

and appreciate all aspects of human connection along the way. 

And to our very human YSM staff, masthead, readers, and advisors, we 

sincerely thank you for your continued support. 

About the Art 

Jenny Tan, Editor-in-Chief 

MASTHEAD 

October 2022 VOL. 95 NO. 3 

EDITORIAL BOARD 

Editor-in-Chief 

Managing Editors 

News Editor 

Features Editor 

Special Sections Editor 

Articles Editor 

Online Editors 

Copy Editors 

Scope Editors 

Website Editor 

PRODUCTION & DESIGN 

Production Manager 

Layout Editors 

Art Editor 

Cover Artist 

Photography Editor 

BUSINESS 

Publisher 

Operations Manager 

Advertising Manager 

Subscriptions Manager 

OUTREACH 

Synapse Presidents 

Synapse Vice President 

Synapse Outreach Coordinators 

Synapse Events Coordinator 

WEB 

Web Managers 

Head of Social Media Team 

Social Media Coordinators 

STAFF 

Sanya Abbasey 

Luna Aguilar 

Ricardo Ahumada 

William Archacki 

Dinesh Bojja 

Risha Chakraborty 

Kelly Chen 

Gia-Bao Dam 

Leah Dayan 

Chris Esneault 

Erin Foley 

Mia Gawth 

Simona Hausleitner 

Tamasen Hayward 

Katherine He 

Miriam Huerta 

Sofia Jacobson 

George Karadzhov 

Jenna Kim 

Catherine Kwon 

Charlotte Leakey 

Charlize Leon Mata 

Ximena Leyba Peralta 

Yurou Liu 

Samantha Liu 

Helena Lyng-Olsen 

Kaley Mafong 

Georgio Maroun 

Alexandra Martinez- 

Garcia 

Cindy Mei 

Lee Ngatia Muita 

Lea Papa 

Hiren Parekh 

Himani Pattisam 

Emily Poag 

Madeleine Popofsky 

Tony Potchernikov 

Zara Ranglin 

Yusuf Rasheed 

Alex Roseman 

Ilora Roy 

Ignacio Ruiz-Sanchez 

Noora Said 

Jenny Tan 

Tai Michaels 

Maria Fernanda Pacheco 

Madison Houck 

Alex Dong 

Sophia Li 

Cindy Kuang 

Ethan Olim 

Tori Sodeinde 

Breanna Brownson 

Hannah Han 

Kayla Yup 

Anna Calame 

Hannah Huang 

Meili Gupta 

Catherine Zheng 

Ann-Marie Abunyewa 

Brianna Fernandez 

Malia Kuo 

Anasthasia Shilov 

Jenny Wong 

Jared Gould 

Lauren Chong 

Sophia Burick 

Shudipto Wahed 

Krishna Dasari 

Lucy Zha 

Rayyan Darji 

Hannah Barsouk 

Risha Chakraborty 

Bella Xiong 

Katherine Moon 

Emily Shang 

Anavi Uppal 

Abigail Jolteus 

Elizabeth Watson 

Jamie Seu 

Pranet Sharma 

Kiera Suh 

Yamato Takabe 

Joey Tan 

Kara Tao 

Connie Tian 

Van Anh Tran 

Sheel Trivedi 

Robin Tsai 

Sherry Wang 

Elise Wilkins 

Aiden Wright 

Elizabeth Wu 

Nathan Wu 

Johnny Yue 

Iffat Zarif 

Hanwen Zhang 

Lawrence Zhao 

Celina Zhao 

Matthew Zoerb 

This issue’s cover depicts a firefly! 

Fireflies, beyond being a beautiful 

source of luminescence, have 

been used to study potential Rev 

inhibitors which may be used to 

create novel HIV antivirals. 

Anasthasia Shilov, Cover Artist 

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

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

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

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

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

NEWS 

Ecology & Evolutionary Biology / Environmental Science 

HUMMINGBIRDS: 

MASTERS OF 

COLOR 

REPURPOSING 

THE URBAN 

FOREST 

BY SHEEL TRIVEDI 

BY ELISE WILKINS 

IMAGE COURTESY OF FLICKR 


What comes to mind when you think of hummingbirds? 

You might think of their rapid heart rate. Or maybe 

their lightning-fast wing speed. But hummingbirds 

have another superpower under their beak: color. 

Bird feathers, known as plumage, display many hues. Researchers 

at Yale University calculated the hummingbird plumage color 

gamut, a value representing the color diversity of hummingbird 

plumage as seen by other birds. Birds see ultraviolet and visible 

light, whereas humans can only see the latter, so human vision 

falls short when considering hummingbird plumage. 

Gabriela Venable (YC ’19), a researcher on the study, spent 

hours at the Peabody Museum and American Museum of Natural 

History using a spectrometer to gather colorful spectra from 

1,600 plumage patches on 114 hummingbird species. “We can 

plot the spectra into a [model accounting for bird vision] and 

calculate the volume from all the points in the model, and that 

can measure color diversity,” Venable said. 

The data revealed that the hummingbird gamut was, in some aspects, 

more diverse than the previously calculated gamut of all other birds 

combined. One justification points to hummingbird barbules, which 

are micro-structures in a feather. “[Barbules] allow [hummingbirds] 

to make saturated colors and many different color combinations,” 

Venable said. This strengthens hummingbird evolutionary benefits, 

like defending floral patches or attracting mates. 

Though they discovered new information about coloration 

mechanisms in birds, there is still work to be accomplished. 

As the first study targeting one family of birds, this research 

facilitates more in-depth analyses of plumage color diversity and 

increases the accuracy of the calculated avian color gamut. ■ 

Trees in urban areas contribute to pollution control and 

enhance biodiversity. But what happens to dead leaves, 

fallen branches, and other forms of tree waste that 

pile up along curbs? Typically, tree waste is sent to landfills 

or incinerated, what experts call the “end-of-life” states. Each 

year, these methods release much of the twenty million metric 

tons of carbon generated by the urban forest as methane and 

carbon dioxide, contributing substantially to global warming. 

To explore the possibilities for circular utilization of tree 

waste, researchers at the Yao Lab at Yale studied five methods 

of tree waste repurposing. Researchers found that the 

optimal scenario consisted of composting leaf waste, selling 

lumber as logs or wood chips, and using residue to produce 

biochar—a substitute for traditional charcoal. Kai Lan, a 

postdoctoral associate on the study team, told the Yale School 

of the Environment, “This aligns with the circular economy 

concept—turning waste into something of value. But it’s not 

just traditional waste like paper and plastic. Tree waste is 

very important, too.” This valuable process can reduce global 

warming and eutrophication—when water sources become 

overrun with nutrients and algal growth, deteriorating water 

quality. Additionally, the benefits extend to stimulating the 

economy through lumber sales and the possibility of new jobs 

to facilitate tree waste management. 

While cities may see differing benefits depending on their 

abundance of tree waste, the study offers new insight into the 

benefits of implementing a circular economy in a surprising 

area, demonstrating that even plants in their “end-of-life” state 

still have much to contribute. ■ 


Medicine / Medicine & Biochemistry 

NEWS 

THE IMPACT OF 

YOUTH ARRESTS 

ON HEALTH IN 

T 

SOCIETY 

ZOMBIE CELLS 

BY JOHNNY YUE 

BY MIA GAWITH 


IMAGE COURTESY OF DAVID ANDRIJEVIC 

Arrests and incarceration have been pertinent issues in 

society for decades. Destiny Tolliver, an assistant professor 

in the pediatrics department at the Boston University 

Chobanian & Avedisian School of Medicine, has recently 

discovered a startling correlation between arrests and health. 

Tolliver and her team analyzed data from the National Longitudinal 

Study of Adolescent to Adult Health, examining cohorts from 1994 

to 2018. They gathered information about participants’ sex, race, 

and ethnicity, as well as the timeline and occurrence of arrests and 

different physical and mental health measures, including clinical 

biomarkers for diseases such as hypertension and diabetes. 

Her analysis found that arrests made before the age of twenty-five 

were associated with higher rates of suicidal thoughts, depression, 

and worsening general health scores. On top of that, youth arrest 

and related policies didn’t impact all communities equally. “There 

are well-documented racial and socioeconomic disparities in who 

experiences arrest, with Black children and children in lowerincome 

households disproportionately impacted,” Tolliver said. 

Contributing to the problem is the minimum juvenile 

prosecution age, which is currently only ten for the state of 

Connecticut. “I think Connecticut can do more in this area by 

raising the minimum age at which children can be prosecuted 

in the juvenile court system to at least fourteen years of age, and 

instead focus on diverting youth to health-promoting systems in 

their communities,” Tolliver said. 

So what’s next? Many states have already implemented changes 

to decrease the number of young people who are arrested. 

Tolliver hopes to research the effects of these modifications on 

youth health to create a model for other states to follow. ■ 

Images of the “living dead” linger in our minds: Frankenstein 

resurrecting his monster, zombies stumbling around with 

contorted limbs, and what seems to be a never-ending 

stream of episodes of “The Walking Dead”. But is it possible 

to bring a mammal back from the dead? A research team at 

the Yale School of Medicine says yes, at least on the cellular 

level. Using a new technology termed OrganEx, scientists 

have successfully restored cellular functions in dead pigs. 

A team of scientists explored the possibility of preventing 

cell death in large mammalian bodies. Per Yale University’s 

ethical guidelines, the scientists induced fatal cardiac arrest 

in female pigs. An hour after their death, these same pigs were 

hooked up to the OrganEx system, a two-part device equipped 

with oxygenation machines and a synthetic solution. Since 

cells do not die instantly, this technology allowed researchers 

to intervene during the cell death process and reverse it. The 

changes were remarkable: oxygen and metabolic levels went 

back to normal, circulation was restored, and organs showed 

fewer signs of damage than with previous technology. 

While not the key to zombies, this discovery answers 

important issues in healthcare. For David Andrijevic, a 

leading co-author from the department of neuroscience, 

the potential applications are staggering. “If you can 

recover the organs after loss of blood flow for so long, then 

we might actually increase an organ donor pool for organ 

transplantation,” Andrijevic said. Future developments will 

focus on expanding these results to the clinical setting. 

Perhaps zombies should take a hint from scientists—how 

else will fiction become a reality? ■ 



NEWS 

Chemistry / Physics 

Anthracene-phenol-pyridine 

(An-PhOH-Py) triad 

EXPANDING 

CHEMISTRY 

A novel fundamental 

chemical reaction opens 

door to new technologies 

BY GEORGE KARADZHOV 

PHOTOGRAPHY BY EMILY POAG 

Last August, a collaboration between the Hammes-Schiffer 

and Mayer groups at Yale and researchers from the 

Hammarström group at Uppsala University led to the 

discovery of a new fundamental photochemical reaction relevant 

to our understanding and application of chemistry. 

The finding follows unexpected results the groups observed in 2019 

when working with the motif anthracene-phenol-pyridine (An-PhOH- 

Py), which contains the three chemical groups connected by single 

bonds. The teams found that when different variations of the An-PhOH- 

Py motif are excited with light, only some of their molecules go through 

a known pathway: the molecule starts at the ground state, the anthracene 

subunit absorbs light energy, and that new energy promotes an electron 

to move from the phenol subunit to the excited anthracene (*An). At the 

same time, a proton transfers to the pyridine unit to form a new chargeseparate 

state (CSS). This CSS represents a different arrangement of 

charge and energy in the molecule that can be utilized later in reactions 

like photosynthesis. The researchers discovered that molecules return 

from the CSS to the ground state through a proton-coupled electron 

transfer (PCET) process that is slowed down by increasing the driving 

force. Surprisingly, the groups did not observe any CSS for certain 

variations of their molecules. Speculating that there was some other way 

for these molecules to react to light and yield a lower energy product, 

researchers computationally predicted and experimentally detected the 

formation of a local electron-proton transfer (LEPT) excited state in 

place of a CSS for some of their reagents. 

The LEPT itself isn’t new. A PhOH-Py molecule can be excited to 

trigger an excited-state proton transfer and give us a *PhOH-Py LEPT 

species. Similarly, the PhOH-Py fragment in the An-PhOH-Py triad 

can be excited to a LEPT state (*PhOH-Py). The direct transformation 

from the excited anthracene fragment in the An-PhOH-Py triad 

to the excited PhOH-Py fragment LEPT (as confirmed by further 

experiments), however, goes beyond existing theories, hinting at a new 

photochemical reaction responsible for these observations. 

With further research, it became clear that that was exactly the 

case! Researchers described a new reaction where a proton transfer 

within the PhOH subunit is coupled to an energy transfer from 

the *An to the PhOH subunit without a charge separation. Rather 

than the reaction involving proton and electron movement, it 

relies on a proton and energy moving throughout the molecule in 

a new way that had never been observed. 

This reaction, appropriately coined a proton-coupled energy 

transfer (PCEnT), also challenges our rules about light absorption 

and fluorescence. Since the energy to excite the LEPT state comes 

from the *An, the fluorescence energy from the *An has to match the 

absorption energy of the PhOH-Py. However, according to Coraline 

Tao, a senior PhD student in the Hammes-Schiffer Lab at the time 

of the project and now a postdoctoral researcher at the University 

of Pennsylvania, the observed fluorescence of LEPT from *An runs 

counter to expectation. “[LEPT’s fluorescence [is] counterintuitive 

because [the] energy giver has to have enough energy to charge the 

acceptor, but here they don’t,” Tao said. Where does that extra energy 

come from? The groups show that the proton transfer can physically 

reconfigure the molecule, making this fluorescence possible. The 

details of how the transferring proton couples with the energy transfer 

process, however, are still unclear, prompting questions about how 

spatial relationships contribute to energy movement across molecules. 

Often, fundamental discoveries have a curious tendency to pop up 

in many unexpected places—think the Schrödinger equation used in 

economics. This is no different. PCEnT describes a powerful process 

that could have significant future applications. Since the LEPT product 

is closer in energy to the *An intermediate than other reagents we 

could use to get the same thing, there is now a way of executing this 

chemical transformation using lower excitation energy. According to 

Tao, this could have important implications for designing molecules 

for solar dyes, solar panels, and other technologies to store and 

use photochemical energy. PCEnT may also already be present in 

photosensitive biological systems, and we haven’t thought to look! 

It could be the case that differences between PCET, PCEnT, and 

other photochemical reactions serve as regulatory mechanisms for 

biological pathways. This new knowledge of PCEnT also allows 

researchers to access new configurations and arrangements of 

molecules that could be synthetically or technologically useful. ■ 


Astrophysics 

NEWS 

A TALE OF 

TWO GALAXIES 

An unexpected collision 

behind the formation of 

two dwarf galaxies 

BY HANWEN ZHANG 


Galactic collisions usually resemble a carefully 

choreographed ballroom dance: picture a pair of galaxies 

pinwheeling into each other’s arms, their gravitational 

centers merging together. But in the case of the two dwarf galaxies 

DF2 and DF4—initialed in honor of the Dragonfly telescope that 

captured them—researchers suspect the cause of their formation 

might have been closer to a collision between two bullets. 

The van Dokkum Lab, a Yale astrophysics research group, proposed 

a bullet-dwarf collision model which describes an event where 

a pair of galaxies run into each other with enough speed to form 

two entirely new ones in their wake. The model is a culmination of 

years of observation and careful telescopic tracking. Van Dokkum’s 

research team first discovered DF2 and DF4 sometime around 2018. 

Both galaxies are members of a space neighborhood roughly sixtyseven 

million light years away from Earth. 

What surprised the group was the virtual absence of any dark matter 

in both DF2 and DF4. The researchers were baffled by the speeds of the 

galaxies’ stars. “They [had] very low velocity dispersion, which means 

that […] these galaxies don’t contain a lot of dark matter,” said Zili Shen, 

a graduate researcher in the lab. The intensity of gravity directly dictates 

the motion of stars, and since most of a galaxy’s gravitational force comes 

from dark matter, both DF4 and DF2 must be strikingly devoid of it. 

Dark-matter deficient galaxies are uncommon—they are so 

rare, in fact, that DF4 and DF2 remain just a few of the handful 

scientists currently know. This is because most galaxies depend 

on dark matter for their creation. Clumps of dark matter—a 

substance virtually undetectable except by its gravitational 

presence—often serve as whirlpool-like centers that collapse 

clouds of gas. There, temperatures can rise to levels nearly double 

the sun’s surface temperature, giving birth to a sizzling new galaxy. 

Without dark matter to create its stars, DF4 and DF2 must have 

come into existence following a script of their own. Analyzing the 

data, the team reasoned that two-parent dwarf galaxies met side-on 

in a high-speed collision, generating an extraordinary amount of force 

that compressed their clouds of gas. This might have been enough to 

form DF2 and DF4. “High-speed collision of dwarf galaxies is a viable 

explanation for galaxies without dark matter,” Shen said. 


Under normal conditions, the comparatively lower speeds 

would have trapped the dark matter of both parent galaxies 

and caused them to merge. But for DF4 and DF2, the collision 

likely occurred with so much velocity that the two haloes of dark 

matter simply bypassed each other. With nothing left to bind 

their constituent star clusters together, the once-organized parent 

galaxies scattered apart. The result: diffuse clouds of gas and stars 

strewn across space, the DF2/DF4 duo among them. 

Their data seems to confirm this. The group’s most recent 

paper identified a linear arrangement of seven to eleven dimlylit 

objects, exactly the kind of structure they would expect to 

find from a cosmic collision like this. Most structures were also 

abnormally large for their relative brightness, offering further 

evidence that they might be the galactic shrapnel of interest. 

But like the star clusters of newly formed galaxies, the model 

remains hazy. At least two other competing theories have 

attempted to explain this phenomenon. One suggests that DF4 

and DF2 simply arose after a normal dwarf galaxy drifted too 

close to a larger galaxy and lost its dark matter. It fails, though, 

to explain the presence of two dark-matter deficient galaxies. 

The second—the tidal dwarf theory—proposes that they arose 

from gas that was stripped off from larger galaxies, but the lab 

has since disproven this through the age and metallicity of both 

galaxies’ constituent stars. 

For now, the bullet-dwarf collision remains a tentative—if 

attractively convincing—hypothetical scenario. “This is mostly 

a theory that explains the data we already have,” Shen said. 

Confirming the bullet-dwarf collision will require more empirical 

evidence, which includes calculations of the individual clusters’ 

velocities and positions. The group has already started processing 

data from the Hubble Telescope to further validate their theory. 

Studying dwarf galaxies like DF2 and DF4 has its benefits. 

Shen explained that dwarf galaxies, being almost one thousand 

times smaller than our Milky Way, are relatively easier to model. 

That doesn’t make piecing together our strange cosmic past any 

simpler, but it might just help reveal new ways of being and of 

becoming that we had previously not known. ■ 


NEWS 

Molecular Biology 

THE 

MOLECULAR 

CLOCK 

Modifying the dynamics 

of cellular movement 

BY CHRISTOPHER ESNEAULT 

PHOTOGRAPHY BY JESSICA LE 

Albert Einstein once said: “The distinction between the 

past, present, and future is only a stubbornly persistent 

illusion.” Time is an idea that has been talked about and 

debated for centuries. For physicists, philosophers, and others in 

between, the meaning of time and space and temporality has kept, 

and will continue to keep, people wondering. 

Though some may believe that judgment of time is only left 

to complex, multicellular organisms, that is not quite true. In 

fact, researchers in Andre Levchenko’s lab at the Yale University 

Systems Biology Institute are currently looking into the cellular 

mechanisms that drive the molecular clock: a new way of 

conceptualizing time on a cellular level. 

Researchers found this clock is controlled by two negative 

feedback mechanisms mediated by microtubule polymerization, 

GEF-H1, and GTPase RhoA. GTPase RhoA is a Ras homolog 

family member A that regulates actin reorganization, a mechanism 

that plays a role in cell migration and motility. Sung Hoon Lee, a 

postdoctoral researcher from the Levchenko Lab, said that though 

his background is actually in electrical engineering, he wanted to 

help build a systems-level understanding of a biological network. 

Why do cells actually migrate? Lee said that it is because cells are 

dynamic in nature, and thus, cells migrate, proliferate, communicate, 

and die. For example, in the case of extreme and unwanted cell 

dynamism, metastatic cancer cells migrate throughout the body to 

invade other tissues. Levchenko joined in this explanation, saying 

that “when an organism develops, there are many cases of cells 

undergoing movements to undergo relocalization.” This dynamic 

cellular movement and reorganization rarely occur in adults, where 

cells are generally pretty settled in the body. However, “the general 

idea for the cells is to figure out how to move and successfully 

relocalize to the desired location,” Levchenko explained. 

While cell movement is normally studied in two-dimensional settings 

like Petri dishes, very little research has dug into the mechanisms of 

movement in three-dimensional settings like the body. In these threedimensional 

settings, cellular activity is controlled by a squeezing motion 

from the posterior end of the cell that propels the cell forward. However, 

little is understood about how this squeezing movement operates. 

Lee found that cells navigate the three-dimensional 

extracellular matrix—the complex network of molecules and 

proteins that forms the connective tissues between cells—using 

a periodic squeezing movement. The molecular clock controls 

the frequency of these squeezing movements and, consequently, 

the speed of cell movement. Furthermore, this clock is 

mediated by two coupled negative feedback loops. “Microtubule 

polymerization is an important component that can enhance 

the abundance of the molecule GEF-H1,” Lee said. This rapid 

polymerization of tubulin inside the cell underpins the dynamics 

of cell movement. “Microtubule polymerization can also inhibit 

the activity of GEF-H1. These two feedback loops modulate the 

molecular clock’s frequency,” Lee continued. 

Furthermore, Lee found that cellular migration was mediated 

by cyclic changes in a small molecule called GTPase RhoA. And 

this GTPase RhoA is dependent on the activity and abundance 

of GEF-H1. By understanding the players underpinning cell 

migration, Lee was able to manipulate the frequency of the 

clock and make cells move, in some cases, three times as fast as 

they normally would. Funnily enough, Levchenko said, “For a 

while, the American Society for Cell Biology had an annual cell 

race where you could put engineered cells on race tracks and 

compete with other cells. While the competition does not take 

place anymore, Sung Hoon would likely win the competition.” 

And while the research conducted by Lee has proven valuable 

in our present understanding of the dynamics of cell movement, 

the implications of his findings are arguably even more valuable. 

Through perturbation of the molecular clock’s frequency, they 

can potentially find new ways of controlling the speed of cell 

movement. In theory, manipulation of this clock could speed up 

the rate at which the repair of cell tissues occurs. Conversely, 

in the case of cancer metastasis, this same clock that controls 

aggressive tumor cells could be slowed down. 

Looking towards the future, it is clear that, with the help of 

the scientific progress made by Lee and Levchenko, the field 

is on the brink of tremendous possibilities regarding systems 

biology and the molecular clock. ■ 


Applied Math 

NEWS 

SOLVING THE 

UNSOLVABLE 

A novel approach to 

calculating a key 

Fourier series 

BY EMILY SHANG 


Have you ever wondered about the math behind a radio signal? 

Or telephones? Scientists who study electromagnetic 

physics and mathematics constantly are: their work is 

founded upon partial differential equations. These equations are 

unlike the differential equations we encounter in calculus: they 

are three-dimensional and extremely difficult to solve because 

they vary with both time and space, even for simple shapes. As a 

result, designing cell phone antennas and radio telescopes is extremely 

challenging. To solve these wave equations, scientists use 

a technique that separates the part which varies with time and the 

part which varies with space, also known as “Helmholtz’s equation.” 

However, Helmholtz’s equation is still a differential equation, 

which is hard to solve. Scientists have been using a trick called 

Green’s functions to solve these sorts of problems for over a hundred 

years. Green’s functions are powerful techniques that let you 

solve a differential equation by computing an integral, making the 

solution easier to attain. However, even though they can convert 

these problems from differential equations into integral equations, 

they still have to do it in 3D, which is extremely hard. 

However, for certain types of symmetric objects, like a radar 

dish, there is a trick that turns a 3D problem into a 2D problem. 

However, it comes at a price. The Green’s function would have 

to be split up into its individual frequencies using the Fourier 

series technique. For each frequency, a very difficult integral, 

called “the modal Green’s function,” would have to be computed. 

This Green’s function is tricky: it oscillates incredibly quickly 

between massive positive and negative values, but somehow, 

they all end up adding up to something tiny. Any attempt to 

estimate the integral by “adding it up” essentially adds and subtracts 

infinity trillions of times, causing so much error that the 

estimate is useless. Scientists have been struggling with how to 

compute this integral since the 1960s. 

To handle difficult integrals, mathematicians will often solve 

them using complex analysis, the field of math that studies imaginary 

numbers. Real numbers are plotted on the “real line,” ranging 

from negative to positive infinity. In contrast, complex numbers 

have a real and imaginary components, meaning they live 

in a 2D space called the “complex plane.” Amazingly, for many 

functions, the integral can either be computed along the real line 

or as a “contour integral” through the 2D complex plane, a technique 

invented by the mathematician Augustin-Louis Cauchy in 

the nineteenth century. By carefully choosing the contour, sometimes 

those integrals can be made very simple. For example, some 

functions oscillate between negative one and positive one on the 

real line, but in the complex plane, they never oscillate. 

For decades, scientists had written off using this contour trick 

because no matter which contour they picked, part of the Green’s 

function wildly exploded and oscillated. James Garritano, along 

with his mentors Yuval Kluger, Rokhlin, and Kirill at the Kluger 

Lab in the Yale School of Medicine, recently overcame the oscillations 

of Green’s function by ignoring the real line and integrating 

it into the complex plane by using a contour invented in 2010 by a 

scientist named Mats Gustafsson. The key idea of their paper was 

to replace part of the Green’s function with an approximation that 

does not grow in the complex plane. Then, they could use Gustafsson’s 

contour and avoid wild oscillations. 

“Dr. Kluger and Dr. Rokhlin, who I work for, are both famous for 

creating fast algorithms to solve problems in physics and genomics,” 

Garritano said. For example, with his student Leslie Greengard, 

Rokhlin created the fast multipole algorithm, named one 

of the top ten algorithms of the twentieth century. It became the 

basis for a wide range of physics simulations ranging from modeling 

gravitational bodies to electrons. Kluger recently developed 

the fastest method for clustering data in single-cell experiments by 

using insights from computational physics to accelerate one of the 

key algorithms of data science. 

This work has paved the way to create ultra-fast physics solvers 

for rotationally symmetric objects such as antennas and radar dishes. 

Also, their work showed that Cauchy’s contour-trick could be 

applied to more problems than previously thought. ■ 



FOCUS 

Women's Health 

PERSONAL MATTERS 

ON ABORTION 

What we can learn 

from abortion 

storytelling and its 

impact on stigma 

BY VAN 

ANH TRAN 

On June 22, 2022, the United States 

Supreme Court overruled Roe v. 

Wade, which provided constitutional 

protection for the right to abortion for nearly 

half a century. Two months after the decision 

was overturned, over twenty million women 

in the United States lost access to elective 

abortions in their home states. 

The New York Times published a piece 

sharing the stories of people who got abortions 

before Roe stating that an important part of 

advocating for abortion is learning from the 

experiences of Americans who have had 

unsafe abortions before the court decision. On 

Twitter, Representative Alexandria Ocasio- 

Cortez trended for sharing her personal 

sexual assault story during an abortion rally. 

In the video, she told the crowd that she was 

glad to know she at least had a choice if she 

did end up being pregnant because of readily 

accessible abortion care in New York City. 

In 2017, Abigail Cutler YSPH '19, a doctor 

and clinical instructor in the Department of 

Obstetrics and Gynecology at Yale School of 

Medicine, noticed the increased prevalence 

of abortion storytelling in social media 

campaigns. Many of these campaigns’ 

messages were to normalize abortions and 

denounce the stigma associated with it so that 

those who had or were seeking care feel like 

they are not alone in their experience. 

These campaigns inspired Cutler 

to examine whether forms of public 

storytelling—in which storytellers don’t 

necessarily know their audience—could 

decrease community-level abortion 

stigma or the stigma people feel towards 

others who seek or have abortions. 

This stigma commonly manifests as 

discrimination against 

people who have abortions 

and structural barriers 

against abortion care. 

Evidence from years of 

polling research shows clearly 

that the public tends to be most 

supportive of abortions involving 

rape, incest, threats to maternal life, and fetal 

anomalies—none of which reflect the most 

common reasons people seek an abortion. 

“We know these stories are already effective 

for warming public opinion,” Cutler said. 

However, she endeavored to know whether 

“non-exceptional” stories—stories centered 

on the most common circumstances for 

seeking abortion—would impact the hearts 

and minds of the public. 

Formation of the Study 

ART BY 

LUNA 

AGUILAR 

To test this, Cutler’s team conducted 

a randomized trial on a large, nationally 

representative set of U.S. adults selected 

using the Ipsos Knowledge Panel. They 

showed the subjects three videos of people 

sharing their abortion experiences. They 

then measured community-level stigma 

immediately after showing the videos and 

then in a three-month follow-up. 


Women's Health 

FOCUS 

The authors developed a conceptual 

model to measure community-level abortion 

stigma and its facets. This model measures 

stigma through three scales: one primary 

scale measuring judgment (Community 

Abortion Attitudes Scale), one measuring 

how the context of an abortion affects opinion 

(Reproductive Experiences and Events Scale), 

and one measuring expectations of silence and 

secrecy surrounding abortion experiences 

(Community Level Abortion Stigma Scale). 

The crucial part of this experiment was the 

selection of the three videos of people telling 

their experiences, which would be shown to 

the audience. Cutler recognized that, as a cis 

white woman leading a research team of white 

women, the group needed to be mindful of 

how their biases could adversely affect their 

study design. They formed an advisory 

board with racially and ethnically 

diverse members with professional 

or personal backgrounds in 

abortion stigma and storytelling, 

including several non-profit 

abortion organizations. 

The essential qualities 

welcomed an intersectional 

analysis and would include 

speaking to the common 

reasons for seeking abortions, 

the ease or boundaries faced 

with healthcare, and whether the 

speaker told their story in a fluid and 

thoughtful manner. They sought to curate 

videos that would give the viewer a different 

perspective on abortions. “We wanted to 

make the watcher look at abortion in a 

different way, in a way not highlighted every 

day in the media,” Cutler said. 

After developing a scoring matrix for the 

videos based on these essential qualities, the 

advisory board members selected three final 

videos to showcase various abortion stories. 

One video talked about a parent who had 

multiple abortions before. Another video 

was about a woman who spoke about the 

barriers to obtaining an abortion in Texas and 

who traveled to California for the procedure. 

The final video was on a Latina woman who 

attempted to acquire birth control through 

the military and was facing difficulties doing 

so. Before she got deployed, she became 

pregnant. She spoke about how she made the 

decision to get an abortion in the context of 

her family and her values. 

“People don’t make these decisions 

in a vacuum, they don’t make it by 

themselves,” Cutler emphasized. These 


videos were chosen because they reflected 

the intersectionality and politicized nature 

of the abortion conversation through real, 

lived experiences of the most common 

demographics that seek an abortion. 

Reflecting on the Results 

The results of the study showed that 

intervention exposures to these three videos 

both immediately after watching and three 

months later showed no association with 

decreased stigma by the judgment scale 

(CAAS) or the silence and secrecy scale 

(CLASS). This means that exposure to these 

three different abortion stories did not 

lower community-level stigma. Although 

“Abortion storytelling can 

also help other people 

who have abortions who 

feel less alone. 

happen to see that 

” 

story 

there was a decrease in stigma in the 

context scale (REES) immediately after 

watching the videos, it was not significant 

after a three-month follow-up. 

This study approached the question of 

non-intimate storytelling and communitylevel 

stigma from a neutral standpoint, 

meaning that stories were not chosen 

because of their potential to elicit a response 

but to represent non-exceptional abortion 

ABOUT THE AUTHOR 

stories. Furthermore, lack of an effect could 

mean that intervention exposure could be 

dose-dependent and that a single exposure 

to storytelling would not be enough for 

a long-term change in community-level 

stigma but rather should be more frequent 

and prolonged. For instance, a social media 

campaign, such as #ShoutYourAbortion, 

could prolong exposure to abortion stories 

over the period of time that it is trending. 

Furthermore, newspapers such as The 

New York Times creating a section called 

Abortion News could also keep the abortion 

conversation present in the public’s mind. 

“I think it’s important to acknowledge 

the limitations of this study,” Cutler said, “I 

don’t think a takeaway from the findings of 

this study is that abortion storytelling does 

not have the power to change hearts 

and minds. It was one study, and 

it was conducted several years 

ago. The legal landscape is really 

different now.” She mentions that 

repeating this study, especially 

now post-Dobbs, would be 

interesting to see. 

Cutler emphasized that the 

results of this study do not mean 

that abortion storytelling isn’t 

important for other reasons. It 

is essential to recognize that the 

purpose of abortion storytelling 

is not just to change public opinion. 

People who decide to disclose their abortion 

experiences to the general public do so for 

various reasons, such as to feel empowered 

and take the reigns over an experience that 

ought to be discussed more. 

“Abortion storytelling can also help other 

people who have abortions who happen to 

see that story to feel less alone," Cutler said. 

"And that is arguably equally, if not more 

important, than changing public opinion.” ■ 

VAN ANH TRAN 

VAN ANH TRAN (SY '24) is a Molecular, Cellular, and Developmental Biology major from South 

Windsor, CT. She has been involved in YSM since her first year at Yale. Outside of YSM, she is 

involved in Yale Rotaract Club, volunteers at HAPPY and Saint Francis Hospital, and interns at 

the National Alzheimer’s Buddies organization. Van Anh has done IBD research at the Abraham 

lab in the Yale School of Medicine. Van Anh enjoys watching movies with her friends, trying 

different types of coffee, and hanging out with her family. 

THE AUTHOR WOULD LIKE TO THANK Dr. Abigail Cutler for her time and enthusiasm about her 

research on abortion stigma. 

FURTHER READING 

Cutler, A. S., Lundsberg, L. S., White, M. A., Stanwood, N. L., & Gariepy, A. M. (2021). Characterizing 

community-level abortion stigma in the United States. Contraception, 104(3), 305–313. https:// 

doi.org/10.1016/j.contraception.2021.03.021 


FOCUS 

Medicine Biology 

USING FIREFLIES 

TO MEASURE HIV 

REPLICATION 

Co-opting bioluminescence for retroviral drug development 

BY CONNIE TIAN 

Have you ever seen a field of fireflies? If 

you have, you were probably thinking 

about how magical the experience was. 

Or maybe you were wondering how these insects 

somehow evolved the ability to bioluminescence. 

But chances are you were not thinking about how 

firefly luminescence would be a great tool for 

measuring protein-protein interactions. 

A History of Co-opting Bioluminescence 

The phenomenon of bioluminescence, 

which is the biochemical emission of light by 

living organisms, has fascinated humans for 

millennia and has been exploited for just as 

long. Roman naturalist Pliny the Elder wrote 

that one could create a torch by rubbing the 

slime of a luminous jellyfish onto a walking 

stick. In the 17th century, physician Georg 

Rumphius documented how indigenous 

peoples of Indonesia used bioluminescent 

fungi as flashlights in forests. Then, in 1875, 

Raphel Dubois reported the first in vitro 

demonstration of bioluminescence. 

Dubois made two extracts of the 

bioluminescent clam Pholas, one with hot 

water and another using cold water. The light 

in the cold sample eventually disappeared. 

Furthermore, when he heated the hot sample 

to near boiling, the glow stopped. But when he 

mixed those two samples together, he observed 

light emission once again. Dubois concluded 

from his observations that a key aspect of 

bioluminescence comes from a heat-stable 

organic molecule he named luciferin and an 

enzyme called luciferase. Today, we understand 

that luciferase is an enzyme that catalyzes a 

light-producing reaction in the presence of 

oxygen and the naturally occurring substrate, 

luciferin. But scientific interest 

in the chemistry of the luciferinluciferase 

reaction didn’t stop there. 

Currently, there are dozens of 

assays that rely on the activity of 

luciferase enzymes. For example, the split 

firefly luciferase complementation assay 

(SLCA) uses bioluminescence to quantify 

protein-protein interactions within 

living cells. The assay uses modified 

firefly luciferase (FFLUC) split into two 

pieces, named N-FFLUC and C-FFLUC. 

On their own, the two pieces of FFLUC 

are inactive and do not luminesce. 

When the N-FFLUC and C-FFLUC are 

brought into close proximity in the presence 

of oxygen, ATP, and magnesium, the FFLUC 

will oxidize to produce light. This system 

can be adapted to measure the interactions 

between any two small proteins by fusing 

each of the two interacting proteins to the 

N or C terminus of luciferase. When the 

two proteins bind and interact, it brings the 

N-FFLUC and C-FFLUC close together so 

that FFLUC will luminesce. The luminescence 

can then be quantified with a machine called 

a luminometer, which will provide insight 

into the level of protein interaction. 

Human Immunodeficiency Virus 

Recently, Yale undergraduate Tucker 

Hansen YC '22 and his mentor Richard 

Sutton developed an SLCA to quantify the 

Human Immunodeficiency Virus type 1 

(HIV-1) Rev-Rev interaction. The assay 

will identify inhibitors that specifically 

prevent the Rev-Rev interaction of HIV-1 

to stop infections. 

H u m a n 

immunodeficiency virus 

(HIV) is a virus that attacks the body’s 

immune system. While there are two common 

subtypes, HIV-1 and HIV-2, most people 

living with HIV have HIV-1. The virus infects 

CD4+ T cells, a type of white blood cell also 

known as helper T cells. These cells help fight 

infection by triggering the immune system to 

destroy pathogens in the body. In active CD4+ 

T cells, infection is caused by the insertion of 

the viral DNA into the host genome and its 

subsequent expression into new viral particles. 

When left untreated, HIV-1 replication causes 

progressive loss of CD4+ T cells, raising the 

infected individual’s susceptibility to infectious 

diseases that would not usually cause illness in 

a healthy individual. 

There are currently over thirty-eight million 

people living with HIV-1. Most patients 

can maintain undetectable viral loads and 

near-normal life expectancy with the help of 

antiretroviral medications that inhibit HIV- 


Medicine Biology 

FOCUS 

1 replication. There are currently dozens of 

FDA-approved medications against HIV-1, 

including protease, reverse transcriptase, and 

integrase inhibitors. So why would there be a 

need for more inhibitors? 

A Case for New Inhibitors of Chronic 

Diseases 

Viral suppression through existing 

medications enables immune recovery and 

the near elimination of the risk of developing 

AIDS, the more severe and life-threatening 

stage of HIV infection. However, due to drug 

resistance, some patients do not respond to 

the existing medications well. 

HIV-1 drug resistance is caused by changes 

in the genetic structure of HIV-1 that interfere 

with the ability of medications to block viral 

replication. Since RNA viruses such as HIV-1 

have an especially high mutation rate that allows 

for quicker evolution, all retroviral drugs risk 

becoming ineffective due to the emergence of 

drug-resistant viral strains. Furthermore, drug 

resistance can more easily arise if there is poor 

adherence to prescribed medications. “As with 

any chronic disease, there is always a need for 

improvement in current medications, as well as 

the development of new antivirals,” Hansen said. 

Revving Engines 

The Rev protein is highly conserved in 

all subtypes of HIV and is necessary for 

transporting copies of viral RNA out of the 

nucleus of the host cell. Without Rev, HIV 

would not be able to replicate in its host. An 

essential property of Rev activity is that it must 

multimerize on the Rev-Response Element 

(RRE) of HIV RNA to successfully export 

that RNA from the nucleus to the cytoplasm 

of the host. This means that multiple Rev 

proteins must interact with each other to 

form a multimer. Since the multimerization 

of Rev is key to its mechanism of action, it 

could serve as a small molecule drug target. 

Sutton, an expert studying HIV for years, 

knew that the Rev protein was essential to 

HIV survival. But there are currently no 

HIV antiviral drugs that target the Rev 

protein. “[A Rev inhibitor could] be a firstin-class 

antiviral,” Sutton said. 

Hansen began his project by developing an 

SLCA that could quantify Rev-Rev interaction 

in cells. Hansen fused each of the luciferase 

domains, NLUC and CLUC, to a Rev protein. 

The fused protein was created by genetically 

engineering a fusion gene that combined the 


sequence of the specific luciferase domain 

with the sequence of the Rev protein. Through 

a series of experiments, Hansen and Sutton 

eventually developed a highly sensitive screen 

for measuring Rev-Rev interaction. When Rev 

proteins were close enough to multimerize, 

the NLUC and CLUC would be brought close 

enough to luminesce. This assay works inside 

and outside of cells. Thus, even when using just 

the inner contents of cells, the assay can still 

accurately quantify Rev-Rev interaction. 

The goal of developing this assay is to find a 

small molecule inhibitor that can disrupt the 

Rev-Rev interaction. Hansen demonstrated that 

this assay could help by testing whether mutant 

Revs, which would inhibit the wild-type Rev 

interaction, reduce luminescence levels in the 

assay. Performing the assay with mutated Rev 

proteins fused to NLUC and CLUC resulted in 

much lower luminescence, indicating that this 

SLCA can be used to screen for an inhibitor that 

disrupts the Rev-Rev interaction. Similar to how 

a mutant Rev would not be able to multimerize, 

a putative inhibitor would be able to disrupt 

this interaction and result in a much lower 

luminescence reading. Thus, researchers could 

use this system to test an unlimited number 

of small molecules to see whether any can 

effectively prevent Rev-Rev interactions without 

being an inhibitor of the luciferase enzyme itself. 

When asked whether he could find such an 

inhibitor, Sutton admitted that it was unlikely. 

“Honestly, I don’t think our lab could ever do 

this,” Sutton said. “It really takes a commercial 

entity to do it. Can you imagine Tucker 

screening two-hundred thousand compounds 

on his own?” A pharmaceutical company, 

however, has the means and methods to 

perform large-scale screens to identify 

potential inhibitors of the Rev-Rev interaction. 

PHOTOGRAPHY BY HANNAH HAN 

Associate Research Scientist Edidiong Akang, a new 

member of the Sutton Lab, pipettes fluids into a 

microcentrifuge tube. 

Sutton is currently applying for a grant 

from the NIH to fund the next steps of this 

project. With this funding, he is considering 

partnering with the local pharmaceutical 

company, ViiV Healthcare, which focuses 

on delivering new treatment options for 

people living with HIV. Sutton and Hansen 

are hopeful that the potential Rev inhibitors 

identified through this partnership could 

serve as a new class of HIV antivirals and 

present another line of defense for HIV 

patients with drug-resistance complications. 

The work done by Hansen and Sutton is 

only one of many examples demonstrating the 

versatility in applications of firefly luciferase. 

This story highlights the ingenuity of using 

phenomena in the natural world to create 

tools and technologies that can facilitate our 

understanding of biological processes. As we 

continue to explore and rationalize more of 

the natural world, Hansen and Sutton’s work 

reminds us that existing biological processes 

can be the key to unlocking a whole new 

world of technology and discovery with 

innumerable benefits to mankind. ■ 

A R T B Y K A R A T A O 


CONNIE TIAN is a senior in Grace Hopper studying Molecular, Cellular, and Developmental Biology. 

Connie currently conducts research in the DiMaio Lab at the Yale School of Medicine. Her research 

focuses on engineering genetically expressible, small transmembrane proteins to facilitate the 

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

Club Soccer team, Community Health Educators, and Yale Undergraduate Science Olympiad. 

THE AUTHOR WOULD LIKE TO THANK Tucker Hansen and Dr. Richard Sutton for their time and 

enthusiasm in sharing their research findings. 

REFERENCES: 

CONNIE TIAN 

Jabr, F. (2016, May 10). The Secret History of Bioluminescence. Hakai Magazine. https://hakaimagazine. 

com/features/secret-history-bioluminescence/ 

Rinaldi, A. (2007). Naturally better. Science and technology are looking to nature’s successful designs for 

inspiration. EMBO Reports, 8(11), 995–999. https://doi.org/10.1038/sj.embor.7401107 


FOCUS 

Evolutionary Biology 

THE WORLD IN 

Characterizing 

mammal 

biodiversity 

and evolution 

at the protein 

level 

Into the World of Proteins 

You, me, a worm, and a cow. What 

makes us different? Shape, size, 

personality, and innumerable other 

characteristics create visible differences, of 

course—but all of that is ultimately founded 

on the invisible world of proteins. 

Proteins are the microscopic tools of life, 

each one serving a specific function related 

to communication, catalysis, structure, 

storage, and every other aspect of cellular 

business. By interacting with other proteins 

and biological molecules, proteins generate 

all of life’s characterizing features: birth, 

death, cognition, and 

reproduction, just to name 

a few. 

We can imagine 

understanding an 

organism 

as a 

composite 

of its protein inventory. Almost all of its 

characteristics and behaviors depend on the 

type, number, and activity of its proteins. 

In fact, although we often think about 

evolution solely in terms of DNA mutations 

creating new characteristics, the relationship 

between DNA and an organism's tangible 

features depends entirely on proteins, 

meaning proteins play a crucial role as 

mediators of evolution. 

A Serendipitous Encounter 

Propelled by a protein-focused perspective, 

Yansheng Liu found himself watching 

Gunter Wagner’s presentation on the curious 

case of cow cancer at a seminar on Yale’s West 

Campus. Wagner, an evolutionary biologist, 

was interested in understanding cancer by 

BY KRISHNA DASARI 

comparing 

it between 

species. To 

understand why cows 

are less prone to cancer than 

humans, Wagner had been studying 

connections between changes in gene 

expression—an indirect measure of protein 

levels—and cancer resistance. 

Gene expression can be used to 

approximate protein levels because of the 

“central dogma” of molecular biology: a 

single sequence of DNA, the primary set 

of instructions, is transcribed into many 

copies of RNA. The RNA is then read and 

used to build proteins—the final, functional 

product. Measuring gene expression 

normally means measuring RNA levels, 

and it had long been conveniently assumed 

that protein levels were proportional to 

RNA levels due to the central dogma. 

But this is not always the case. Protein 

levels don’t always follow RNA levels, 

and Wagner was well aware of the longstanding 

debate about how well RNA and 

protein levels correlate. He knew the value 

of measuring protein levels themselves. 

ART BY MALIA KUO 



FOCUS 

PROTEINS 

However, at 

the time, there 

was no practical method 

to quantify protein levels across 

the whole collection of proteins in 

a cell. This lack of technology forced 

him and almost everyone else in the field 

to rely on RNA-based gene expression to 

approximate protein levels. 

This is where Liu comes in. As a proteomicist, 

someone who studies the world of proteins, 

he, like Wagner, had a keen interest in the 

biodiversity of proteins. “I was so inspired by 

Gunter’s talk,” Liu said. “He’s using this very 

different angle to compare species to get a clue 

about human beings…and I quickly related 

[it] to some of my previous work about the 

diversity between human individuals and 

suggested that we could…cover different 

species [with proteomics].” 

Liu wanted to go further than gene 

expression. Rather than approximate 

protein levels using gene expression, why 

not study biodiversity at the protein level? 

And for the first time, he developed the 

technology to answer this question. He 

had been part of a team building a tool to 

measure protein levels called DIA-MS, a 

variant of standard mass spectrometry that 

offers advantages in reproducibility 

and accuracy. With this 

method, he and Wagner 

had the tools and the 

experience to explore 

a new frontier 

with Wagner: 

investigating 

biodiversity 

not with 

approximations 

of protein levels 

but with direct 

measurements. 


Where to Go and 

What to Do? 

While Wagner’s original presentation 

focused on cancer, the two saw value in 

expanding their scope to perform an initial 

survey of protein-centric biodiversity across 

mammals. With the powerful ability to 

quantify complete protein profiles across 

species, Liu and Wagner were now faced 

with the difficult task of choosing what 

questions to ask. 

To both, it was clear that they must provide 

an answer to the fundamental debate: how 

well does RNA-based gene expression 

correlate with protein levels? They could 

test the validity of an assumption that the 

field had been relying on for decades, and 

now in multiple species. 

Beyond this highly practical aspect of the 

RNA-protein relationship, they also wanted to 

investigate the evolutionary history of the RNA 

and protein profiles. Could these two intimately 

intertwined yet distinct bodies evolve together 

across the tree of life? Or do intervening 

mechanisms disrupt the tethers between the 

two, separating the evolution of RNA levels 

from protein levels? We know of many possible 

sources of disruption, such as those that affect 

RNA stability or modify or degrade protein 

independently of RNA levels. Even further, we 

must consider the most significant difference 

between proteins and their nucleic acid 

cousins, DNA and RNA: proteins are the final, 

functional product! They’re made to interact 

with molecules or other proteins; can 

these interactions selectively 

constrain 

o r 

accelerate only 

protein evolution and not 

RNA? 

Consistent with their interest 

in protein biodiversity, the researchers 

were also curious about how their answers 

to these previous questions might vary 

between different species and individuals of 

the same species. Liu had previously revealed 

significant variability in the protein profiles 

of different humans, and they now 

had the chance to extend this 

work across species. 

Finally, 

t h e y 

considered 

what 

unique 

insight they could 

gain from proteins as 

opposed to DNA or RNA. 

Liu expressed interest in 

phosphorylation sites—spots 

on proteins that can bind or release 

phosphate molecules to activate 

or deactivate the protein. These 

sites are responsible for complex 

signaling pathways that regulate 

everything from cell growth and death 

to movement and secretion, so they receive 

much attention for understanding cell 

regulation or designing protein-inhibiting 

drugs. Liu and Wagner gained the ability to 

catalog the biodiversity of phosphorylation 

sites based on actual proteins rather than 

DNA or RNA. 

From fundamental questions of molecular 

biology to structural biochemistry to 

evolution, the new technologies and the 

unexpected collaboration between an 

evolutionary biologist and proteomicist 

thrust a new probe into previously murky 

waters of biology. With so much inbuilt 

potential, they had no reason to constrain 

themselves to one field of questions. “You 

have to use your biological intuition to 

understand what nature is trying to tell us 

here, and that’s fundamentally a creative 

process,” Wagner said. The world of proteins 

had much to tell about every field of biology, 

and Liu and Wagner were there to listen. 

Discoveries from the Protein World 

From their venture, the team 

recorded an invaluable dataset of 

protein diversity amongst mammals. 


FOCUS 


With this in hand, we can finally 

understand what differentiates you and 

me from cows on the protein level, with 

applications to tracking our evolutionary 

histories or informing medical research. 

They also used this data to determine that 

RNA and protein levels are moderately 

well correlated, though far from perfect. 

The good news is that the correlation 

does not invalidate decades of prior gene 

expression work, but it still sheds light on 

the importance of going directly to the 

source: proteins. 

Further, they discovered correspondence 

between variability in RNA and protein 

levels, suggesting that despite the many 

possible disruptions, RNA and protein levels 

do tend to coevolve. The tethers between 

these two spheres of molecular biology 

overall remain strong, though the exact 

relationship is protein-function-dependent. 

For example, some classes of proteins— 

such as those involved in protein 

degradation—show little variation in 

both RNA and protein levels, while 

other classes—such as those filling 

the extracellular region—feature high 

variation in both, contributing to increased 

evolvability. However, certain proteins defy 

this trend. Proteins involved in large protein 

complexes feature less protein variability 

than RNA variability because intimate 

dependence on other proteins pressures 

individual proteins to be less variable. 

Overall, protein profiles were slightly 

more variable than their RNA counterparts, 

suggesting that evolution can occur in 

proteins rather than solely on DNA/RNA. 

Furthermore, Liu and Wagner discovered 

more variability amongst phosphorylation 

sites relative to protein profiles. This 

variability may reflect the evolutionary value 

of tightly regulating protein activity or of 

generating new cell signaling possibilities. 

The team also constructed a network of 

coevolution amongst phosphorylation 

sites, providing insight into the complex 

interactions between signaling 

pathways. 

Finally, Liu and Wagner 

established 

that variability 

in protein 

between 

profiles 

species 

mirrors 

variability 

within 

species. In 

other words, 

PHOTOGRAPHY BY SANYA ABBASEY 

Dr. Yansheng Liu (right), Barbara Salovska (left), Dr. Wenxue Li (middle right), and Dr. Yi Di (middle left). 

if levels of a protein are highly variable 

between humans, they are also likely to be 

variable between humans and other species. 

Returning Home 

We have learned much about the protein 

world, but what do these results mean for 

biology on a broader scale? For one, they 

tell us that we can reasonably trust gene 

expression while still acknowledging that 

protein levels are more variable because of 

their functional role. The data also reveals 

significant diversity in protein profiles not 

only between species but also between 

individuals. And most importantly, Liu 

and Wagner have opened doors for an 

incredible array of studies. Evolution 

can now be interpreted not just from 


changes in the genome, but by studying 

the proteins themselves—the tools that 

perform the tasks that evolution evaluates. 

Biodiversity, disease, and cell biology can all 

be approached from a more protein-centric 

perspective. In essence, a new method of 

understanding biology awaits us. 

Pondering the future of the field, Wagner 

concluded, “It’s still very difficult. It’s 

pioneering, but it’s clear that this is 

the direction it has to go in the long 

run.” Trekking through the protein 

world may remain challenging for 

years to come, but it promises 

to light the way toward a 

pivotal new 

understanding 

of diversity and 

evolution. ■ 

KRISHNA DASARI 

KRISHNA DASARI is a junior in Pierson College majoring in Molecular, Cellular, and Developmental 

Biology with a Certificate in Data Science. As well as writing for YSM he also co-leads the outreach 

branch, Synapse, and conducts research on the evolutionary genetics of cancer at the Yale School of 

Public Health. 

THE AUTHOR WOULD LIKE TO THANK Gunter Wagner and Yansheng Liu for their time and thrilling 

explanations of their research. 


Ba, Q., Hei, Y., Dighe, A., Li, W., Maziarz, J., Pak, I., Wang, S., Wagner, G. P., & Liu, Y. (2022). Proteotype 

coevolution and quantitative diversity across 11 mammalian species. Science Advances, 8(36). https:// 

doi.org/10.1126/sciadv.abn0756 

Wagner, G. (2019, November 25). Can Cows Teach us how to beat Cancer Malignancy? Nature Ecology 

and Evolution. Retrieved October 12, 2022, from https://ecoevocommunity.nature.com/posts/56631- 

can-cows-can-teach-us-how-to-beat-cancer-malignancy 


Theoretical Physics 

FOCUS 

TURNING 

THE KNOTS IN 

RESONATORS 

RESONATORS 

Bridging elegant math and practical physics 

BY YUSUF 

RASHEED 

ART BY 

CHARLOTTE LEAKEY 

What do piano strings, air particles, and colliding comets have 

in common? Each of them is an oscillator, broadly defining 

anything that can vibrate. Oscillators are ubiquitous—they 

can be electrical, mechanical, optical, and astronomical, varying from 

smaller than an atom to larger than a planet. 

Every oscillator has a discrete set of frequencies at which it 

naturally vibrates. These are known as its resonance frequencies or 

eigenfrequencies, collectively known as the object’s spectrum. You may 

have encountered these in physics class in the form 

of standing waves, which are the various waves that 

naturally “fit” into a given object. For a very simple 

object like a guitar string, these are just sine waves, which “fit” whenever a 

half-integer number of their wavelength fits into the length of the string. 

Each wave will vibrate with its own frequency or eigenfrequency, which 

can be changed by adjusting anything that affects the system. In the case 

of a guitar, factors such as the tension of guitar strings, the type of wood, 

and the temperature of the environment can be used 

to tune its spectrum. 



FOCUS 


Physicists know that any oscillator’s 

resonance frequencies are always given 

by the roots of a polynomial equation. 

When the oscillator is free from friction, 

all of the roots of this polynomial are real 

numbers, which is quite reasonable given 

that frequencies are usually thought of 

as real numbers. However, when friction 

is considered in the model, these roots 

become complex. This means that the root 

contains an imaginary number i, equivalent 

to √-1. When the model for an oscillator’s 

resonance frequencies includes friction, 

it is known as a non-Hermitian system. 

In contrast, a Hermitian system does not 

include friction in its model. The complex 

root takes the form (a + bi), where a is 

the real part of the root representing the 

resonance frequency, and b 

is the decay 

rate, or how 

quickly the 

oscillator 

s t o p s 

oscillating. 

O n e 

example 

is a guitar’s 

strings 

coming 

to rest 

after being 

plucked. 

To visualize the relationship between a 

system’s parameters and its spectrum of 

resonance frequencies, it is helpful to use two 

graphs: one showing the parameters that are 

being changed and the other showing the 

system’s resonance frequencies with each 

frequency being a point in the complex plane. 

This pair of two graphs can be seen in the 

figure below with pairs of plots “c” and “f,” 

“d” and “g,” or “e” and “h,” where plots “c,” “d,” 

and “e” are the parameter graphs, and plots 

“f,” “g,” and “h” are the resonance frequencies 

graphs. Continuing the example of a guitar, the 

parameter graph would have the tension in its 

strings, the type of wood, and the temperature 

of the environment, while the spectrum graph 

would have time as its vertical axis, representing 

how far along the control loop we are, and the 

complex eigenfrequencies in the horizontal 

plane. The spectrum graph can be thought of 

as plotting the complex eigenfrequencies in the 

horizontal plane and then stacking these planes 

on top of each other as time passes. When the 

parameters are gradually changed and then 

returned to their original values, a loop is 

formed in the first graph, known as a control 

loop. This control loop can be seen below in 

the figure as the green, red, or blue loop in 

plots “c,” “d,” and “e,” respectively. Such a loop 

may or may not enclose points corresponding 

to a choice of parameters that would produce 

a spectrum in which two or more 

eigenvalues are 

equal, 

known as a 

degeneracy. 

These points can be seen 

below in the figure 

as the points along 

the yellow “trefoil 

knot”-shaped 

structure in plots 

“c,” “d,” and “e.” 

When the parameters are varied 

around a control loop, a “braid” 

topological structure is created in the 

spectrum graph. Much like one can braid hair 

into different styles, these spectral braids also 

can twist and turn in a variety of ways. The 

specific braid that is created depends on the 

manner in which the control loop encloses the 

PHOTOGRAPHY BY MATTHEW ZOERB 

The light beam is guided through several prisms 

before entering the metal cube, where a 50 

nanometer thin piece of silicone nitride is. 

degeneracy points. These braids can be seen 

below in the figure as the triplet of green, red, or 

blue lines in plots “f,” “g,” and “h,” respectively. 

This relationship between polynomials 

and their roots was previously wellunderstood 

for a system with two oscillators 

(N=2). The braid would twist once if the 

control loop encloses a “degeneracy”–a 

point in the parameter graph at which two 

or more resonance frequencies of the system 

are equal. If the control loop does 

not enclose a degeneracy, the 

braid, in turn, does not 

twist. 

T h e 

relationship 

becomes more 

complex for a system 

with three oscillators 

(N=3). Mathematicians have 

known for a long time that the 

degenerate solutions of polynomial 

equations result in a curve/structure with 

non-trivial ‘topology’–the degeneracy curve 

forms a trefoil knot in the parameter graph for 

N=3. Topology is the branch of mathematics 

that deals with the shapes of geometric objects. 

For example, a donut has a different topology 

than a sphere, as the former has a hole 

while the latter does not. This topology had 

historically been almost exclusively explored 

in mathematics, not physics. Physicists knew 

that the braids twisted in various ways, but 

they did not know why, though they knew it 

had something to do with degeneracies. 

This project changed that through the 

combined forces of the Harris Lab and the 

Read Lab, whose researchers elucidated how 

this mathematical relationship defines systems 

with any number of oscillators. In other 

words, N is arbitrary. In addition, they showed 

systems with N=3 already exhibit several 

striking features that are absent from the N=2 

case. Lastly, they demonstrated these features 



FOCUS 

in the measurements of a system with three 

oscillators. Jack Harris and Nicholas Read 

are both Professors of Physics and Applied 

Physics, but Harris is an experimentalist, while 

Read is a theorist. Read was familiar with the 

mathematics of degeneracy curves forming a 

trefoil knot in the parameter graph for N=3 

and thus provided the missing piece to Harris’s 

exploration of how the braids twist. “[Read’s] 

the one who explained all the math to us. It 

happened because I had heard about this field 

and was confused about it… and I knew that 

[Read] knew a lot about math. After multiple 

conversations, we both agreed that this was 

something really interesting and we should try 

and pursue it.” Harris said. 

The groups found that the braiding 

process was defined by how the control loop 

encircled the trefoil knot of degeneracies. 

In the figure from the Nature paper below, 

graphs “c”, “d”, and “e” show the trefoil 

knot topological structure and the control 

loop, which is colored green, red, and blue, 

respectively. When the control loop doesn’t 

enclose the trefoil knot, a trivial braid is 

formed—mathematically, a braid without 

twists and turns is still a braid, just a trivial 

one (graph “f ”), as opposed to when the 

control loop does enclose the trefoil knot, 

the braiding depends on how many times 

the control loop encloses the trefoil knot 

(once in graph “g” and twice in graph “h”). 

“Relating this topology of the degenerate 

roots of polynomials to the physics of 

resonators, and realizing that the twists and 

turns of the braids [in the spectrum graph] 

are intimately related by a mathematical 

correspondence to how the control loop 

[in the parameter graph] entwines with 

that topological structure took us some 

time to develop and appreciate, and then 

experimentally verify,” Patil said. 

The researchers have also experimentally 

confirmed their findings using an 

optomechanical system of three oscillators 

(N=3). The apparatus they used was a 

radiation pressure system with three lasers 

that is analogous to a solar sail. Solar sails use 

large mirrors to reflect photons from the sun 

while traveling in space—each photon has 

momentum that it transfers to the solar sail 

upon impact, resulting in the propulsion of the 

whole spacecraft. Similarly, the apparatus they 

used had three lasers with differing powers 

that were pointed at a vibrating membrane 

of silicon nitride, allowing the researchers 

to control the membrane’s stiffness and 


IMAGE COURTESY OF PATIL ET AL. 

Measurements of the EP2 knot K and the eigenvalue braids.This figure is pulled directly from the paper this 

article focuses on, which is cited below. 

damping and, thus, its resonance frequencies. 

Three different colors were also used; red, 

green, and blue, adding another dimension to 

the experiment. The researchers empirically 

saw for this system of N=3 oscillators that 

the topological structure of degeneracies in 

the parameter graph is indeed a trefoil knot. 

They saw that the twists in the experimentally 

realized braids indeed correlate with how the 

control loop entwines this trefoil knot. 

In addition to Professor Harris and Professor 

Read, both Dr. Yogesh Patil and graduate 

student Judith Höller played key roles in the 

project’s success. Patil ran the experiments, 

working with the lasers and oscillators. “[The 

project] was very demanding in terms of the 

sheer amount of time and [precision] with 

how the system needed to be controlled. 

[Patil] provided two years of solid leadership 

and guidance through the pandemic. This 

whole project happened during lockdown 


because he was able to take [it on].” While 

Patil was in the lab, Höller was a crucial bridge 

between Harris and Read. “It was clear from 

the start that Nick’s elegant story about the 

math could–in principle–be realized with 

the equipment in our lab. But making this 

translation was too complicated at first. It was 

Judith who made this translation possible. 

The three of us had many long conversations 

in which Nick would describe the theory, 

and then Judith would explain it to me. Then 

I would describe what we could do with the 

lasers, and Judith would explain it back to 

him. She was a key catalyst,” Harris said. 

Given the ubiquity of oscillators, 

this discovery opens the door to future 

improvement of any system that contains 

them, including computers, radios, and 

watches. Technological advancements in this 

area no longer need to be limited to systems 

with only two oscillators. ■ 

YUSUF RASHEED 

YUSUF RASHEED hails from the Bay Area and is a sophomore in Trumbull College majoring in 

Biomedical Engineering. He has a deep interest in physician-patient relationships and how budding 

medical professionals can develop their soft skills during and after their education. He hopes to apply 

his experience in engineering to a clinical setting in the future by improving and personalizing patient 

care. Yusuf also believes in the power of writing to effect change at all levels, whether that’s personally 

through a journal or publicly through the Yale Scientific Magazine. He encourages all interested 

students to get involved with the magazine and try their hand at writing an article. 

THE AUTHOR WOULD LIKE TO THANK Professor Jack Harris and Dr. Yogesh Patil for their valuable 

time and support for this article. 

FURTHER READING: 

Patil, Y.S.S., Höller, J., Henry, P.A. et al. Measuring the knot of non-Hermitian degeneracies and noncommuting 

braids. Nature 607, 271–275 (2022). https://doi.org/10.1038/s41586-022-04796-w. 


FOCUS 

Biomedical Engineering 

HOW TO 

GROW 

A HEART 

Accelerating 

the maturation 

of engineering 

heart tissues 

BY CATHERINE ZHENG 

ART BY KIERA SUH 



FOCUS 

Imagine a world where any organ 

could be grown in the lab. A sample 

from a cheek swab could become a 

functioning heart in just a matter of weeks. 

New hearts would be grown from patients’ 

stem cells whenever they were needed, 

and organ transplant lists and waiting 

times would virtually disappear. 

While this world is still far in the future, 

researchers at the lab of Stuart Campbell, 

Yale Associate Professor of Biomedical 

Engineering & Cellular and Molecular 

Physiology, have taken major strides in 

accelerating the maturation of stem-cell 

derived cardiomyocytes (iPSC-CMs) to 

grow engineered heart tissues (EHTs) in 

the lab that can even contract in response 

to electrical stimuli. 

Growing Fetal Heart Cells 

The primary function of EHTs is to 

provide a model of the human heart to 

study its features and responses to stimuli 

without having to access a human heart 

directly. These models are created by 

differentiating induced pluripotent stem 

cells into cardiomyocytes—specifically, 

stem-cell derived cardiomyocytes 

(iPSC-CMs). This process involves first 

washing a thin slice of a pig heart in a 

detergent to clear away pig cells. The 

extracellular matrix is then used as a 

template for seeding a mixture of human 

heart cells, including iPSC-CMs and 

human cardiac fibroblasts. 

However, since stem cells can differentiate 

into any type of cell, iPSC-CMs are still 

relatively immature, representing fetal 

cardiomyocytes rather than mature ones. 

This limits their functionality as studies on 

them may not represent the characteristics 

of a fully grown human heart. Thus, to 

accurately represent mature heart tissue, 

iPSC-CMs need to undergo a maturation 

protocol that can currently take anywhere 

from forty days to six months. 

One proposed technique for speeding 

up the maturation of iPSC-CMs is 

progressive electrical ramp pacing, which 

involves exposing the cells to an increasing 

rate of electrical current pulses over time. 

Previous studies have shown that this leads 

to heart cells that are more mature as they 

have more advanced electrophysiology 

and better calcium handling. 

Calcium is also known to play a large 

role in cardiac physiology, as it is essential 

in inducing the contraction of the heart. 

When a membrane potential reaches the 

cardiac muscle, calcium channels open, 

allowing calcium to flow in and bind to 

troponin, which triggers the heart muscle 

cell contraction. Greater calcium levels 

increase contractile force. However, 

calcium’s role in the maturation of EHTs 

has not been previously considered. 

Most EHTs were grown in solutions 

containing only a fraction of the calcium 

concentration normally found in the heart. 

“When our group realized how 

underutilized and underrated those 

calcium mediums have been across the 

field, we thought it might be interesting 

just to try it out,” said Shi Shen, the primary 

researcher on this study. This curiosity 

led to the discovery that difference in 

response to calcium in these early stages 

can be a key driver in cardiomyocyte 

differentiation: results show that the 

amount of calcium present in the cell 

culture medium produced a significant 

change in the maturation of iPSC-CMs. 

Growing Mature Heart Tissues 

To further advance the maturation of 

iPSC-CMs, researchers tested whether 

the combination of electrical ramp 

pacing and an increase in free calcium 

ions, Ca 2+ , in culture could produce a 

scalable improvement in the maturation 

of EHTs compared to the standard 

maturation protocol. 

Four groups of EHTs—high-Ca 2+ nonpaced 

(HC-NP), low-Ca 2+ non-paced 

(LC-NP), high-Ca 2+ ramp-paced (HC- 

RP), and low-Ca 2+ ramp-paced (LC-RP)— 

were studied to determine the effects of 

electrical pacing and calcium level on 

their own and in conjunction. The team 

performed the ramp pacing at frequencies 

higher than that of a regular human heart 

rate. “The regular human heart rate would 

fit between one to two hertz, so putting 

it at three hertz is like putting a YouTube 

video at two times speed,” Stephanie Shao, 

an undergraduate researcher on this study, 

said. “You can really increase the frequency 

and speed it up without harming it. In this 

case, it benefits it because it makes the 

EHTs mature at an accelerated rate.” 

To test the functionality of these 

heart tissues, a variety of metrics were 

measured, ultimately showing that the 

HC-RP group performed much better 

than the other groups. One of the most 

notable improvements was the forcefrequency 

relationship (FFR). FFR 

reflects increases in the contractile force 

of the heart with increasing frequency 

stimulus. “This is one of the key results 

to determine whether our experiments 

are successful because healthy humans 

need this particular phenomenon to 

function, [...] and one of the hallmarks 

of a cardiac disease is the lack of increase 

in force,” Shen said. 

FFR is measured using a mechanical 

testing apparatus that measures force 

in response to 0.25-Hz increases in 

frequency from 1 to 3 Hz. While high 

calcium marginally improved the FFR 

of the groups with no ramp pacing, 

both groups still showed a negative 

FFR, meaning the force continuously 

decreased rather than increasing to a 

systolic peak force and dropping again. 

However, once the researchers induced a 

ramp pacing, they saw a positive FFR in 

the group with high calcium, whereas the 

FFR of the low calcium group was still 

negative. Healthy human myocardium 

has a positive FFR of up to 2-2.5 Hz, 

similar to that of the HC-RP group, 

which exhibited a FFR around 2 Hz. 

PHOTO COURTESY OF STEPHANIE SHAO VIA JENNA KIM 

Microscope image of heart tissue in a relaxed state (left) and a contracted state (right). 



FOCUS 


PHOTOGRAPHY BY JENNA KIM 

Undergraduate researcher Stephanie Shao working with the custom apparatus used to study the engineered 

heart tissues. 

Other metrics that measure heart tissue 

functionality are time-to-peak (TTP) and 

time-to-fifty percent relaxation (RT50). 

TTP is the time it takes for the tissue to 

reach its peak force, and RT50 is the time 

it takes for the tissue to reach fifty percent 

relaxation after its peak contractile force. 

Human tissues exhibit TTP and RT50 

values at around 200 ms and 120 ms, 

respectively. The HC-RP group showed a 

similar TTP of around 290 ms and RT50 

of around 120 ms, which is significantly 

faster than the other EHT groups. 

The effect of isoproterenol (ISO) on the 

EHTs was also observed by measuring 

FFR after exposure to ISO. ISO is a 

drug that increases the contractility of 

the heart. It is used for patients with 

weakened hearts to improve cardiac 

output. The increase in the systolic 

peak force for the HC-RP group was 

much more significant compared to the 

increase in the systolic peak force for 

the LC-RP group. These results indicate 

that the HC-RP group behaves more 

similarly to actual mature heart tissue in 

the presence of ISO. 

On top of these metrics, western blots 

and RNA sequencing were performed 

to analyze changes in protein and RNA 

levels on a molecular level that may have 

influenced improvements seen in the 

different groups. The results showed that 

markers associated with mature heart 

tissues were elevated in the HC-RP group. 

They also found that the genes expressed 

in the HC-NP and LC-RP groups were not 

the same, indicating that both electrical 

ramp pacing and high calcium are needed 

to produce the mature characteristics 

achieved in the EHTs. 

Growing Hearts 

With this improved protocol, the 

maturation of iPSC-CMs can be 

significantly shortened relative to 

previously published techniques. While 

EHTs cannot be used to grow hearts 

directly from stem cells, this advancement 

has significant implications for future 

research. Given that many researchers 

around the world are using iPSC-CMs 

for a variety of purposes, this technique 

has the potential to find widespread use 

and make mature, functional EHTs more 

readily available. 

“For something like a drug study, a lot 

less compound would be used,” Shao said. 

“Especially if it’s a drug that’s not out yet, 

you have to have a chemist make it, and 

that’s not easy to make large quantities of, 

which is what you would need for an in 

vivo study.” 

Another major advantage of using 

EHTs is that they are grown from stem 

cells derived from a specific patient. 

This means that any testing a patient 

may need to undergo can be performed 

on an EHT grown from their stem cells, 

which will more accurately represent the 

characteristics of their own heart. 

This study is a catalyst for future cardiac 

research exploring the vast applications of 

EHTs. “There’s a large segment of work that’s 

being done targeted towards implanting 

cells back into patients to repair the heart 

to replace or regenerate heart muscle,” 

Campbell said. “I would hope that the 

field takes notice of our protocol because 

if you’re repairing the heart, for instance, 

you want to generate a lot of mature cells, 

so someone’s going to have to decide how 

to treat those cells so that they’re as mature 

as possible.” Campbell hopes this paper will 

contribute to the growing body of literature 

for the most optimal maturing conditions. 

Moving forward, there are still other 

factors to investigate that may further 

improve the maturation of stem cells for 

EHT growth. “Something that we haven’t 

tried is combining a realistic pattern 

of mechanical loading, or maturation 

of mechanical loading—so what a 

fetus experiences in terms of the fetal 

heart versus a newborn versus an adult 

heart—modulating the mechanical load 

in conjunction with those heart rate 

changes”, says Campbell. While growing 

a functioning adult human heart is not 

yet in the cards, we are getting closer to a 

future where that is possible. ■ 

ABOUT THE AUTHOR CATHERINE ZHENG 

CATHERINE ZHENG is a senior BME and CS major in Pauli Murray College. In addition to writing for 

YSM, she is the magazine’s production manager, she does research with Professor Staib, and is also the 

production manager for the Yale Undergraduate Research Journal. 

THE AUTHOR WOULD LIKE TO THANK Professor Campbell, Dr. Shi Shen, and Stephanie Shao for their 

time and enthusiasm in sharing their research. 


Shen, S., Sewanan, L. R., Shao, S., Halder, S. S., Stankey, P., Li, X., & Campbell, S. G. (2022). Physiological 

calcium combined with electrical pacing accelerates maturation of human engineered heart tissue. Stem 

Cell Reports, 17(9), 2037–2049. https://doi.org/10.1016/j.stemcr.2022.07.006 


PAPER POWER 

Sustainable Energy 

FEATURE 

A WATER-ACTIVATED 

BIODEGRADABLE PAPER BATTERY 

BY CINDY MEI 

ART BY LUNA AGUILAR 

With great power comes great responsibility. In an age 

where the world has become increasingly reliant on 

technology, the threat of electronic waste or e-waste— 

including many discarded products containing batteries—has 

become increasingly dire. In 2019 alone, an estimated 48.6 million 

tons of e-waste was generated worldwide, a rapidly expanding 

issue that has only continued to grow. Because standard lithium 

batteries contain non-biodegradable and often toxic rare earth 

metals, the accumulation of e-waste releases harmful chemicals 

that can contaminate groundwater and the air, putting the 

environment and the health of billions at risk. 

The quest for green power seeks to eliminate the threat of e-waste 

by harnessing sustainable materials. This pursuit fascinated Gustav 

Nyström, head of cellulose & wood materials at the Swiss Federal 

Laboratories for Materials Science and Technology. By harnessing 

natural, environmentally-friendly materials, researchers in Nyström’s 

lab were able to power the crystal display of a LED alarm clock using 

a disposable paper battery activated by just two drops of water. 

The project, which also involved postdoctoral researcher 

Alexandre Poulin and doctoral researcher Xavier Aeby, sought 

to search for an environmentally-friendly battery high in 

density, important for a longer run time, that 

would be suitable for single-use devices 

such as sensors. “For instance, in 

biomedical industries, where 

many diagnostic tests are 

discarded after a single use due 

to hygienic and ethical reasons, 

there is a lot of plastic waste 

being generated,” Nyström said. 

An electrochemical battery 

stores and discharges energy through 

a series of oxidation and reduction 

reactions that occur at the anode 

and cathode, respectively. In 

addition to these components, a 

separator prevents the electrodes 

from coming in contact and 

short-circuiting, while the electrolyte 

facilitates the movement of ions between the anode and cathode. 

In battery fabrication, the material choice for these components 

is especially important for optimized, reliable function. “We 

made a strict selection based on what we thought were the most 

promising materials in terms of energy density and stability for this 

development,” Nyström said. “It’s about choosing the right type of 

materials that are not harmful to our environment. That’s a big and 

important goal for us.” 


The ideal material is stable and highly conductive, with low 

contact resistance, high energy storage capacity, and a fast charging 

rate. After testing many combinations, the final design used a 

zinc anode, a graphite carbon air cathode, a paper separator, and 

a water-based salt electrolyte. The electrodes were stenciled onto 

the paper using multi-material inks that contained a mixture of 

ethanol, shellac, and sodium chloride ions which are required to 

form the conductivity needed in the battery for electron flow. The 

dry batteries can then be stored indefinitely until water is added, 

which permeates the paper membrane, dissolving the salt ions and 

activating the battery within twenty seconds. 

The battery inks were characterized by shear thinning behavior and 

yield stress, physical factors important in additive manufacturing. 

This method adds components by layering them and has great 

advantages in reducing manufacturing waste. “[Our goal is] also 

being responsible with the amount of material used,” Nyström said. 

“When you manufacture, you only need to use exactly the amount of 

multi-material inks that you need for those different components.” 

The researchers also performed electrochemical tests on the battery. 

A single cell demonstrated a 1.2 V potential, which is proportional 

to the energy delivered to the cells. Power capability was measured 

to reach 150 μW, enough to power 

an alarm’s LCD crystal display, 

hearing aids, and electronic 

watch calculators. With more 

printed batteries added in 

series, the voltage increases, 

accommodating devices with 

greater power usage. After one 

hour of operation, the voltage 

decreased as the paper substrate 

dried. However, upon the readdition 

of water, the performance was 

recovered, allowing for extended 

battery life by increasing how 

much water the paper could hold. 

In the future, the researchers 

hope to study the length of battery 

life following rehydration of the 

battery and explore further implementations of organic materials. 

Nyström believes that it has the potential to play a valuable part in 

the reduction of e-waste in powering single-use diagnostic tests and 

sensors, but there is still much work to be done. “We have had a lot of 

academic developments, and now is really the time to see what and 

how much can be transferred into real products,” Nyström said. “I 

think [paper] is quite a promising material, but we need to see what 

is feasible and where the best applications will be.” ■ 


ART BY EMILY 

BY KAYLA 

FEATURE 

Climate & Oceans 

LIGHTNING’S 

ACHILLES HEEL 

POAG 

YUP 

HOW SEA SPRAY PUTS LIGHTNING TO SLEEP 

In Greek mythology, any site struck by lightning is considered 

sacred. By that logic, the Earth’s land must be divine—a whopping 

ninety percent of lightning strikes land, leaving only a measly ration 

for oceans worldwide. Thanks to a study recently published in Nature 

Communications, we now know the secret to this phenomenon. Above 

the ocean, wind and water interact to form sea spray: salty particles 

suspended in the air. Scientists in Israel, China, and the US discovered 

that this spray could reduce lighting by up to 90 percent. 

Clouds are composed of droplets that typically form when 

water vapor condenses onto aerosols. The term ‘aerosol’ refers to 

any small solid particle suspended in the air. Previous research 

found that ‘fine aerosols,’ such as smoke, can encourage lightning 

formation by serving as sites for condensation. This has been 

used to link rising rates of air pollution to increased lightning. 

“Lightning is sort of the byproduct of clouds,” said Yannian Zhu, 

study co-author and associate professor at Nanjing University. 

“Normally, if you don’t have clouds, you don’t have lightning.” 

For clouds to become ‘electrified,’ they must reach a certain 

elevation. Rising currents of air—updrafts—help clouds grow to 

a height at which the temperature is below zero degrees Celsius. 

At this level, water droplets can freeze into ice crystals. Some 

of these ice crystals then collect the rest of the water droplets, 

forming larger sleet-like particles known as ‘graupel.’ The other 

ice crystals remain small and positively charged and continue to 

be pushed by updrafts toward the top of the cloud. 

Meanwhile, the graupel descends, carrying a negative charge. 

Electrical charge is transferred from the 

crystals to 

the graupel when they 

collide. 

O v e r 

time, an 

electrical 

field builds 

from the 

c o n s t a n t 

transfer of 

electrical 

charges 

between 

t h e 

oppositely 

charged 

particles. 

A f t e r 

sufficient 

buildup, the power of the electricity is strong enough to penetrate 

through the atmosphere, discharging as a flash of lightning. 

On land, fine aerosols are much more concentrated, largely due to 

air pollution, making them the main source for cloud formation. Over 

oceans, sea spray frequently serves as a condensation site, forming 

water droplets bigger and heavier than their fine aerosol counterparts. 

Fine aerosol particles are small and abundant, forming 

clouds with numerous small droplets. These droplets are slow 

to combine into raindrops, remaining small enough to ascend 

easily to a high enough level for freezing to occur. However, sea 

spray, which is considered a ‘coarse aerosol,’ has the opposite 

effect: large droplets form and quickly coalesce into rain. 

The large salt particles in sea spray can absorb water quicker and 

easier, forming large droplets that eagerly collect other droplets. 

As a result, these clouds will rain out too soon before reaching the 

sub-zero temperature height at which ice can form and electrify 

the cloud. This phenomenon also helps explain why small rain 

showers are more frequent over the ocean than on land. 

“If you live beside the sea, you will see that there are many [rain] 

showers every day without thunderstorms—just showering,” Zhu 

said. “It is a cycle, water vapor becomes clouds, and then the 

clouds become rain [and so on] ... this energy transition between 

surface and atmosphere is very fast.” 

The researchers drew upon over four years of satellite data 

measuring clouds, precipitation, aerosols, and meteorology. “In 

principle, people knew that the added sea spray particles enhanced 

rainfall, but they never had such comprehensive measurements from 

satellites to actually [demonstrate] the effect on a global scale,” said coauthor 

Daniel Rosenfeld, a meteorologist and professor at the Hebrew 

University of Jerusalem. “It’s one thing to know that something, in 

theory, could happen; it’s another thing to see that it is [in fact] really 

significant and has a large effect.” This study ultimately differentiated 

the contrasting effects of fine and coarse aerosols on clouds. 

Current weather prediction and climate models fail to consider 

the effect of sea spray on weather patterns. Knowing how aerosols 

can change the cloud’s physical processes will enable us to monitor 

convective clouds more accurately and potentially artificially alter 

them to avoid natural disasters, such as hail and tornadoes. Simply by 

deploying the right aerosols into the air, the practice of ‘cloud-seeding’ 

has facilitated China’s attempts to trigger more rainfall for agriculture. 

“Our responsibility is to understand the whole aerosol-cloud 

interaction microphysical process and to give that knowledge… 

to help people do future climate predictions more accurately,” Zhu 

said. “We’re trying to save the world in a different way.” ■ 


Robotics & Medicine 

FEATURE 

Black Mirror. Ex Machina. The Terminator. Why does 

television seem to vilify robots and artificial intelligence 

as a human invention bound to go wrong? Why are robots 

always portrayed as a perilous design destined to eradicate the 

human species? We see this smear of these intelligent machines 

in the media and pop culture, from movies that follow the 

expedition of an assassin robot to dystopian shows that alarm 

their audiences about the dangers of unrestricted technological 

advancements. However, let us not forget that robots are 

designed to facilitate human conventions and tasks, with 

great potential to revamp and advance biotechnology, medical 

procedures, and clinical treatments. 

In one of the latest clinically transformative 

cases, researchers at Stanford University 

designed a tiny origami robot capable of various 

movements in physiological environments to 

deliver organic cargo and liquid medicine. We often 

attribute origami to the Japanese paper-folding 

craft, but this technology fulfills the robot’s 

multifunctionality based on the geometric 

features of a specific origami structure: the 

Kresling. The Kresling is a triangulated 

hollow cylinder where ‘twist buckling’ a 

thin cylindrical sheet creates triangular 

elements throughout the structure. The 

twist buckling mechanism can be created 

by folding one sheet slightly higher than 

the next sheet, then repeating this process 

along the direction of the twist. Because 

the Kresling structure is always curved 

at the folds, the junctions between folds 

can be radially cut for liquid drug release. 

The buckling effect and high geometrical 

symmetry of the design allow for the robot’s 

sphere-like ability to roll, flip, and spin. 

“The Kresling origami is a special design 

that couples torsion—a twisting motion—and 

compression, which provides us with the foldability to 

develop a pumping mechanism for targeted drug delivery,” 

said Renee Zhao, assistant professor of mechanical 

engineering at Stanford University and one of the 

leading scientists on the project. The robot is 

prepared by attaching thin magnetic plates to the 

ends of the Kresling structure, which generates a 

twisting force as the robot’s rigid body rotation 

aligns with the magnetic field. 


TINY 

ORI 

AM R G I 

THE FUTURE OF DRUG DELIVERY 

BY IGNACIO RUIZ-SANCHEZ 

OB OTS 

This all sounds very compelling and groundbreaking, but how 

does the robot’s origami structure improve the drug delivery 

process? After all, the robot is not being introduced to a generally 

dry environment, so why is on-ground locomotion relevant? 

Zhao and her team at Stanford characterize the tiny robot as 

amphibious in functionality, meaning that the robot can navigate 

both complex ground and aqueous environments. “On-ground 

locomotion is based on the robot’s interaction with a solid surface 

by rolling and flipping, and aquatic locomotion is based on the 

spinning mechanism that creates propulsion for the device to 

swim,” Zhao said. The magnet plates also activate the pumping 

mechanism to release liquid medicine into the body. 

For drug delivery, a needle and a liquid medicine 

container are inserted into the internal cavity of 

the robot. Once the device reaches the target 

area, the magnetic plates activate a rotational 

force to contract the robot, during which the 

needle punctures the liquid container. Gradually, 

the Kresling’s internal cavity shrinks and squeezes the 

liquid medicine out through the radial cuts into the environment. 

Similarly, the spinning-enabled feature from the magnets also 

allows for cargo loading and release, which follows the same 

locomotive process as the pumping mechanism. However, it first 

propels the robot to absorb solid objects from an environment, 

stores those objects in the internal container, and finally releases 

them via pumping once the robot reaches the target area. 

Despite the relatively small size of the millirobot, the internal 

cavity of the Kresling is still widely unoccupied, even after 

installing the needle and liquid container. Researchers 

have thus built sensors and cameras in the cavity to direct 

movements and record specific environmental conditions. 

“The internal cavity of the robot can actually be 

used to integrate other functional components, 

like cameras for biopsies and biosynthetic tissues 

to stop internal bleeding,” Zhao said. The potential 

biomedical applications for using the robot and its 

internal compartments are vast. 

Versatility, agency, and efficacy all seem to 

be leading features in the architecture of these 

innovative devices. Robots like the Kresling origami 

should remind us that robots were created to help us, 

not harm us. To this point, let’s stop giving robots such 

a bad rap in pop culture, especially if these cute, foldable 

robots could be designed to ultimately save our lives. ■ 

ART BY CATHERINE KWON 


FEATURE 

Developmental Psychology & Artificial Intelligence 

WHAT CAN A COMPUTER 

LEARN FROM A BABY? 

TEACHING PHYSICAL INTUITION TO AI MODELS 

BY NATHAN WU 

ART BY CATHERINE KWON 

Before we turn three months old, 

humans have already developed 

an intuitive sense of how the 

physical world works. If an infant knocks 

over a block tower, they know the blocks 

will tumble spectacularly down to the 

ground. If the blocks float in the air or 

fall straight through the floor, the infant 

might cry out in surprise. 

This sense of common intuition is 

dubbed our ‘intuitive physics engine,’ 

fundamental to both biological and 

artificial intelligent systems operating 

in the real world. Understanding how 

a system’s physical actions will affect 

the world around them can guide what 

decisions and movements they must 

execute to carry out their intentions. In 

biological systems, the intuitive physics 

engine develops extremely rapidly, 

suggesting its importance for survival in 

the physical world. 

Despite the ubiquity of 

intuitive physics in 

intelligent 

biological 

organisms, the best artificial intelligence 

(AI) systems still struggle to replicate 

the same understanding of physics that 

even very young children have mastered. 

This difficulty continues despite the great 

progress made in the field. AI systems 

easily best humans in complex games, like 

Chess and Go, and have solved some of 

the most complicated scientific 

problems, like protein 

folding. The challenge of 

teaching intuitive physics 

to an artificial system lies 

within its pervasiveness. 

“Intuitive physics is everywhere, 

and when something 

is everywhere, it 

becomes hard to analyze because it’s 

interacting with so many things,” said 

Luis Piloto, a research scientist 

at DeepMind, 

a subsidiary of 

Alphabet, Google’s 

parent company. 

However, Piloto’s 

team has 

recently made great 

strides toward finding 

a solution by taking 

inspiration from the methods 

and findings of developmental 

psychology, ultimately 

creating an AI system that 

learns intuitive physics 

from visual data. 

Perhaps the most important 

novelty of Piloto’s work was how their 

AI model’s understanding of intuitive physics 


Developmental Psychology & Artificial Intelligence 

FEATURE 

was probed and evaluated. In developmental 

psychology, intuitive physics is separated 

into several distinct concepts, such as object 

permanence or object solidity. For each 

concept tested individually, human subjects 

are shown relevant scenes that are either 

consistent or inconsistent with the concept 

of interest. If subjects show surprise after 

seeing inconsistent scenes, which is usually 

measured by gaze duration, there is evidence 

that the subject understands that concept. 

This method of evaluating intuitive physics 

knowledge is known as the violation-ofexpectation 

(VoE) paradigm. 

Inspired by these methods used in 

developmental psychology, Piloto and 

his team constructed the Physical 

Concepts dataset. This dataset contains 

videos generated by a physics engine, 

each consistent or inconsistent with one 

of five distinct concepts from intuitive 

physics. These concepts included object 

permanence (objects will not simply 

disappear), object solidity (objects 

will not pass through one another), 

continuity (objects will have continuous 

paths and cannot teleport from one place 

to another), unchangeableness (objects 

retain their properties over time), and 

directional inertia (objects will stay in 

their path unless a force acts upon them). 

Every video that abided by a concept 

was paired with a visually similar one 

that violated that concept, both starting 

with identical scenes but deviating over 

the course of the video. The amount of 

'surprise' that a model exhibited was 

determined by the model’s prediction 

error—how different a future scene 

predicted by the model is compared to 

the real future scene in the accompanying 

video. Thus, the model’s understanding of 

a concept can be evaluated by examining 

the difference in the model’s surprise 

in response to physically plausible and 

implausible pairs of videos. 

This VoE paradigm is a departure 

from standard methods of evaluating 

AI’s performance on intuitive physics 

tasks. One common approach utilizes 

video prediction on physically plausible 

situations alone to evaluate learning 

progress. In the VoE paradigm, the 

model should, in theory, make incorrect 

predictions about physically implausible 

videos, enabling researchers to better 

understand whether a concept is truly 

being learned. Another common 

approach employs reinforcement learning 

tasks, whereby models plan actions to 

interact with the environment around 

them to receive a reward. However, 

the complexity of these tasks makes it 

difficult to isolate the true cause of failure 

because success requires intuitive physics 

knowledge and knowledge of how to 

navigate the given space. 

“If we want to evaluate intuitive physics 

knowledge, let's break it down into these 

different concepts, and let’s build stimuli 

that are really about the concepts… 

You can do well on benchmarks, but if 

they don't reflect the capabilities that 

you're actually trying to measure, then 

increasing your performance on those 

benchmarks doesn't necessarily get you 

closer to the capabilities that you want,” 

Piloto explained. 

The next key insight from developmental 

psychology incorporated by Piloto’s team 

was an object-based conception of physics. 

Infant intuitive physics behavior involves 

segmenting the visual field into distinct 

objects with their own properties (object 

individuation), tracking these objects 

across space and time (object tracking), and 

then processing how these objects interact 

with each other (relational processing). 

These three processes were implemented in 

a model called Physics Learning through 

Auto-encoding and Tracking Objects, 

nicknamed PLATO. Rather than only 

looking at patterns of pixels in a visual 

scene as other visual prediction models 

do, each frame that PLATO processes is 

broken down by masking specific parts 

of the scene so that the model can learn 

representations of individual objects. 

Indices assigned to each object enable 

them to be tracked through time. Lastly, 

a separate module is used to process how 

these objects interact with one another and 

predict future scenes. 

After just twenty-eight hours of visual 

training with physically plausible videos 

from the physical concepts dataset, 

PLATO demonstrated a grasp of all five 

concepts by exhibiting greater surprise 

in response to physically implausible 

videos. This result outperformed AI 

models that do not rely on object-based 

representations as PLATO does. The model 

also performed well on a different dataset 

developed independently by a team at the 

Massachusetts Institute of Technology, 

suggesting that PLATO’s understanding 

of intuitive physics is robust. 

The quest to build an AI system that 

can learn intuitive physics is far from 

over. While Piloto’s team at DeepMind 

has taken a great step forward, there is 

still much room for improvement. In 

particular, PLATO did not learn how 

to segment and label the visual field 

into distinct objects by itself. Instead, 

the researchers spoon-fed the model 

a series of masks that told it where 

each object was. Other recent work has 

successfully tackled this challenge, 

introducing methods for object 

discovery in an unsegmented visual 

field. Integrating this research with the 

relational processing module of PLATO 

would result in a seamless model that 

can understand intuitive physics with 

nothing but a video. 

PLATO’s success as a machine learning 

model inspired by biological brains speaks 

to artificial intelligence’s close relationship 

with neuroscience and psychology. “AI 

and neuroscience are attacking the same 

problem from different sides,” Piloto said. 

“The analogy that I like to use is that AI 

is building intelligence from scratch, 

and neuroscientists are saying, ‘Wait, 

hold on, we’ve got this intelligent system 

right here, why don’t we try and reverseengineer 

what’s going on?’” 

Although PLATO is far from being 

an accurate model of intuitive physics 

learning in children, the study still 

presents important implications for 

developmental psychology. PLATO’s 

success proves that intuitive physics 

knowledge is not necessarily innate—it 

can be rapidly acquired through visual 

learning. Additionally, Piloto’s team 

proposes using models like PLATO to 

investigate the order in which different 

intuitive physics concepts are acquired 

throughout development. This study 

demonstrates that the brain sciences 

and artificial intelligence have much to 

gain through work at the intersection of 

the two fields. ■ 



FEATURE 


A LIFE-SAVING 

STICKER 

DEVELOPING 

A BIOADHESIVE 

ULTRASOUND 

DEVICE 

BY XIMENA 

LEYVA PERALTA 

ART BY KIERA SUH 

Diagnosing diseases can be tricky. How 

can doctors tell if a headache stems 

from a lack of sleep or something more 

serious? How can they see what is happening 

inside a patient? Peering inside the body can 

provide valuable, life-saving information 

for clinicians. Among the different imaging 

techniques, ultrasound—a non-invasive, riskfree 

diagnostic tool—stands out as a leading 

option. Researchers at the Massachusetts 

Institute of Technology (MIT) 

have developed a small, adhesive 

device that may revolutionize 

ultrasound technology. 

Ultrasound devices use sound 

waves to create a picture of 

internal organs and tissues. An ultrasound 

probe emits high-frequency waves, which 

can travel through soft tissues but bounce off 

harder structures. An image is then created 

by a computer using these echoes. Thanks to 

its lack of radiation, ultrasound is the safest 

imaging tool, making it an ideal choice for 

continuous monitoring. However, current 

ultrasound devices are bulky and require an 

experienced clinician to operate the handheld 

probe. The clinician can only obtain a few 

images or videos in a regular ultrasound 

appointment, which typically lasts less than 

thirty minutes. Continuous imaging to 

monitor internal changes as the body moves 

on a day-to-day basis is not an option. 

The team at MIT was able to transform the 

standard bulky, handheld ultrasound into a 

simple sticker by developing a brand-new 

bioadhesive that can comfortably attach 

a small ultrasound probe to the skin. The 

resulting bioadhesive ultrasound (BAUS) 

device can be attached to the body for up 

to forty-eight hours at a time to take highquality 

images and videos of our body’s 

activities—blood vessels contracting, lungs 

expanding, stomachs digesting, and hearts 

pumping. The BAUS device can comfortably 

move with the person and capture the 

human body’s natural dynamism. 

“Wearable ultrasound equipment can 

potentially revolutionize medical imaging,” 

said Xuanhe Zhao, professor of mechanical 

engineering and civil and environmental 

engineering at MIT, who co-authored the 

Science paper that describes the BAUS 

device. “Medical imaging is very important 

for diagnostic purposes. However, 

with existing medical imaging, 

the timescale is short. It’s usually 

a few seconds or minutes—just a 

snapshot.” Continuous and frequent 

imaging of internal organs, over 

days or even months, could help 

clinicians more effectively monitor the 

health of patients and observe how diseases 

progress. It could also provide invaluable 

new data about the human body and lead to 

discoveries in medicine and biology. 

The biggest challenge has been comfortably 

attaching an ultrasound probe to the body. 

“It’s really [about] how you can integrate the 

ultrasound device with the body so it can give 

you long-term continuous imaging over days 

even under dynamic body motion,” Zhao said. 

Previous wearable ultrasound devices were 

designed to be stretchable and move with the 

skin. However, this design sacrificed image 

quality and resolution despite the improved 

wearability. Moreover, sound transmission is 

vital to reach deep organs, such as the heart 

or stomach, and accurately image them. 

When using traditional ultrasound devices, 

clinicians apply a gel layer to prevent air 

pockets that can block the transmission of 

sound waves through the skin. However, 

these gels are not designed for prolonged 

use. “The liquid gel, if you put it in contact 

with the body, it can potentially cause 

acidification in a few hours,” 

Zhao explained. Wearable 

ultrasound devices have used 

hydrogels—a water-rich, goo-like 

substance—in the past to solve 



FEATURE 

this problem, but they 

get dehydrated and detach 

after only a couple of hours. 

Other devices use a rubbery 

material called an elastomer 

to attach the device to the 

skin. However, pure elastomer adhesives 

dampen sound waves, preventing them from 

reaching deep organs. 

The beauty of the BAUS device comes from 

a newly developed bioadhesive that combines 

the adhesion capabilities of an elastomer with 

the sound transmission abilities of a hydrogel. 

“For the bioadhesive part, we really spent 

lots of effort to develop a hydrogel-elastomer 

hybrid. It’s very different from existing liquid 

hydrogels that can easily flow away,” Zhao 

said. The new material consists of a hydrogel 

encapsulated by an elastomer to form a soft 

solid that can adhere robustly and comfortably 

to the skin, doubling as an adhesive and 

a gel to improve sound transmission. The 

researchers then embedded a thin highperformance 

probe in the hydrogel-elastomer 

to complete the BAUS. 

They tested its performance over fortyeight 

hours by imaging the various organs 

and tissues of fifteen test subjects. The BAUS 

device showed everything from how blood 

vessels’ diameter increased as a subject stood 

up to how blood flow rate increased after 

thirty minutes of exercise to how the stomach 

emptied over two hours after a subject drank 

a glass of juice. It can also image the heart’s 

four chambers and show how they change 

in size under continuous body motion. 

Furthermore, its success in imaging the 

lungs and the diaphragm means that the 

BAUS could potentially be used to monitor 

respiratory diseases, including COVID-19, 

and prevent further complications. 

IMAGE COURTESY OF FELICE FRANKEL 

The bioadhesive ultrasound device. 

IMAGES COURTESY OF WANG ET AL. 

A bioadhesive ultrasound device adhered to the skin (left) and being detached from the skin (right). 

“I would say it’d be easier for clinicians 

and maybe even patients to [use] this. It’s 

like [adhering] a bandaid on the skin. 

And our lab is currently working to 

further simplify this process,” Zhao said. 

Traditional handheld ultrasound requires 

qualified personnel and can be relatively 

expensive. Apart from continuous 

imaging, the BAUS device provides a 

simplified imaging process that could 

eliminate the need for an experienced 

operator and possibly even give patients 

the option of adhering the device by 

themselves. Hence, the BAUS could help 

increase the accessibility of ultrasounds. 

Clinicians and healthcare professionals 

alike are excited about the broad 

medical potential of the BAUS device. 

Continuous imaging is essential for 

monitoring and tracking tumor growth 

and for early detection and treatment 

of cancer. Diagnoses for conditions 

that involve muscles, joints, and 

bones often require dynamic tests that 

cannot be performed using traditional 

ultrasound techniques. Cardiovascular 

diseases, which affect the performance 

of blood vessels and the heart, can lead 

to dangerous heart attacks that require 

ultrasound technology for diagnosis. A 

wearable ultrasound device could help 

alert those at higher risk for heart attacks 

of changes in their blood pressure 

in time to save lives. Ultimately, 

the BAUS opens up a world of 

possibilities in diagnostic 

practices and 

the continuous 

monitoring 

of patient health. 

However, more steps must be taken 

before the BAUS device can be widely used 

and implemented. The existing device still 

needs to plug into a computer that 

collects and analyzes data. 

Zhao’s team is working on 

making a portable wireless 

version that can truly 

move with a patient and 

be used even when 

there is no access 

to a computer. Zhao 

a l s o 

describes that while the image 

quality of the BAUS probes is superior 

to other wearable devices, his team is 

still working on obtaining higher image 

resolution to match traditional ultrasound 

devices. Clinical trials must also be 

conducted before FDA approval. “In the 

first paper, we only tested healthy people. 

Now, we are applying this system to patients 

to study various diseases,” Zhao said. 

The development of the BAUS device 

is only the latest project that Zhao’s team 

at MIT has been working on as part of 

their mission to advance science and 

technology at the interface of humans and 

machines. The team’s expertise centers 

around materials science, mechanics, 

and biotechnology, but they regularly 

collaborate with experts in other fields 

and engage in intersectional projects. 

“We are really focused on addressing 

multidisciplinary challenges in health and 

sustainability. I believe we are solving some 

of the most important questions facing 

society, and I hope we can contribute to 

their solution,” Zhao said. ■ 



FEATURE 

Biotechnology 

BY RISHA 

CHAKRABORTY 

ELECTRONIC 

SKIN 

Our world is being increasingly defined 

by a series of ones and zeroes. 

From the smallest phone gyroscope 

capable of detecting body movement to metal 

detectors at the airport to automatic PCR 

machines that test for the SARS-COV-2 virus 

in a matter of hours, the technology that 

acquires and transmits this data has made 

human lives much easier. Over the last two 

decades, practical artificial intelligence (AI) 

usage has led to expanding roles for computers 

in detecting danger, predicting scores, 

and advising outcomes in fields ranging 

from security to medicine—often beyond 

the scope of its original creation and with 

limited human intervention. Of course, popular 

debate and science fiction warns about 

how AI may eventually replace humans 

across many fields and make human effort 

obsolete. However, Wei Gao, a professor of 

medical engineering at the California Institute 

of Technology, sees the advancement of 

AI as an opportunity rather than a threat. 

Gao received his bachelor’s degree in mechanical 

engineering and his master’s degree 

in chemical engineering at the University of 

California, San Diego. He completed a postdoctoral 

fellowship in electrical engineering 

at the University of California, Berkeley. Because 

of his diverse educational background, 

he pursued the creation of robots imbued 

with functionalities beyond traditional ones. 

“In our minds, robots are industrial-level, capable 

of doing dangerous tasks in agriculture, 

defense, and space exploration because they 

can move and perform repetitive tasks, but 

we are thinking about the future. How can 

we build a better robot [by giving it] better 

functionalities and making it smarter? How 

can we give it more powerful sensing capabilities?” 

Gao pondered. 

Inspired by human skin’s ability to detect 

temperature, touch, texture, and even certain 

chemicals, for example, an allergic skin 

response after rolling around in the grass, 

Gao set out to develop ‘electronic skin.’ In 

the past, researchers have developed robots 

to detect and respond to physical parameters 

such as temperature and pressure. 

However, they were unwieldy and impractical—not 

much more than a thermometer 

on a remote-controllable stick. Moreover, 

Gao wanted to diversify the sensors in his 

robot so that the electronic skin could have 

an even greater range of sensory capabilities 

than human skin. In particular, he hoped to 

detect infectious pathogens for medical applications, 

neurotoxins or bomb debris for 

security purposes, and chemical pesticides 

for agricultural uses—all harmful or dangerous 

for humans to handle. 

The main problem was designing a method 

to make electronic skin emulate human 

skin. Scientists are only beginning to understand 

how human 'sensors' such as mechanoreceptors 

and thermoreceptors work. In 

fact, the 2020 Nobel Prize in Medicine and 

Physiology was awarded to two scientists 

for discovering the neural mechanisms behind 

human sensations. What would be the 

technological equivalent of millions of nerve 

endings in human skin conferring incredible 

sensitivity and a wide range of detecting 

abilities, and how could such a system be 

built in a reproducible, scalable way? 

With the help of colleagues with expertise 

in materials science and nano-engineering, 

Gao developed electronic skin, which he 

called E-skin-H. “My primary inspiration 

comes from human skin,” Gao said. Touch 

and pressure cause electrical changes that 

can then be converted to computer signals. 

To mimic the vast nerve network of human 

skin, Gao created sensor arrays with microscopic 

radii of detection, increasing both the 

sensitivity and strength of a signal compared 

to using a single large sensor. These properties 

are helpful in complex applications like 

detecting the presence of a specific chemical 

out of a large mixture. 

Embedding such minuscule sensor arrays 

in a highly flexible matrix is a technically 

easier way to create a bridge between sensors 

and robots than integrating the existing 

large chemical sensors meant for analysis 

of dry particles on robots. The flexibility of 

the sensor array material enables E-skin-H 

to retain its sensing capabilities regardless 

of how the actual robotic hand or arm on 

which it is mounted moves. Moreover, by 

using a hydrogel underneath the e-skin interface, 

the robotic skin can test for chemicals 

like they are in solution even though 

the sensor array is technically in a solid state. 

For example, biochemical tests like ELISAs 

can detect specific proteins, like those marking 

the surfaces of a SARS-COV-2 virus, in 

a solution. But now, with the hydrogel, the 

sensor array can detect proteins from a solid 

surface. Perhaps the most brilliant facet of 

Gao’s e-skin is that it can be printed with an 

inkjet printer. It requires only a series of nano-material 

metal inks such as gold, silver, 

and platinum to decorate graphene electrodes 

and a 3D-hydrogel printer. The ease 

of production vastly increases the scalability, 

adaptability, and replaceability of the sensor 


Biotechnology 

FEATURE 

How robots are gaining 

human-like sensing abilities 

ART BY CHARLOTTE LEAKEY 

arrays. It also decreases production costs, 

allowing for the creation of larger sensor arrays 

that can be modified to test for various 

new compounds. 

In his article published in Science Robotics, 

Gao built a robot called M-bot, which 

used machine learning to learn how human 

muscles, specifically hand and arm muscles, 

move in response to detecting certain tactile 

or chemical threats. Gao evaluated E-skin-H 

to see how the skin’s sensing capabilities 

could assist robots in making AI-based decisions 

the same way a human would. He concluded 

that M-bot could be used to detect 

compounds in a contaminated environment 

and track the source of trace amounts of 

hazardous compounds. In an early demonstration, 

M-bot tracked a nerve agent leak in 

an open field by detecting a gradient of the 

compound across the sensor array. By tracking 

the location of the highest concentration 


of the compound, the AI algorithm within 

M-bot was able to signal to the motors 

within the robot arms and fingers to extend 

towards the location of the highest concentration 

to grasp objects and collect samples. 

“It was pretty impressive since it was fully 

automatic,” Gao said. 

Gao sees E-skin-H being used in medical 

and defense applications within the next five 

to ten years. “You don’t want to send a human 

into a danger zone to detect explosives 

or biohazards. Electronic skin can be used in 

military, environmental, and agricultural applications. 

We just have to make the robots 

[that use e-skin] smarter and more automatic—with 

the help of materials science, chemistry, 

and data processing.” Gao said. 

With the foreseeable future wrought by 

AI applications and robotic sensing technologies, 

Gao encourages anyone interested in 

robotics and technology to nurture this interest 

by identifying a problem, understanding 

where there is a gap in current technologies 

that attempt to address this problem, 

and imagining potential solutions. “Becoming 

involved in engineering or robotics is not 

a problem about technology, but more about 

developing a pattern of thinking. Trying 

competitions like FIRST Lego League and 

VEX Robotics inspires young students to 

imagine the fullest potential of robots,” Gao 

said. With this principle in mind, Gao combines 

chemical, medical, electrical, and mechanical 

principles to create solutions to the 

problems that fascinate him. As he expands 

his projects, from robots that use electronic 

skin in defense applications to nano-robots 

that deliver drugs to cells in the body, Gao 

is convinced of their increasing necessity in 

the future. “I’m excited to see how we interact 

with robots in our daily lives going forward,” 

Gao concluded. ■ 


UNDERGRADUATE PROFILE 

Shervin Dehmoubed—sophomore at Yale and stellar 

tennis player—is also a CEO, starting his entrepreneurial 

journey when he was just fifteen. He launched a children’s 

toy company specializing in products for kids diagnosed with 

ADHD/ADD, making a six-figure revenue within the first three 

years. This success fueled his following projects, Pik ‘le’ Ball, a 

pickleball accessory and clothing line, and a software company 

that built iOS apps for health and fitness. These experiences gave 

him the unique perspective and required expertise to launch his 

latest and most successful company, EcoPackables. 

Dehmoubed was shocked to discover how much plastic waste 

even a small brand could produce when working on Pik ‘le’ Ball. 

Thus, he launched a sustainable packaging company that sells 

packaging films made from recycled or compostable materials, 

aiming to find solutions to promote sustainability within the private 

sector. “This was during Covid, and e-commerce was booming, so 

I decided I wanted to do something about this,” Dehmoubed said. 

The key technology is a compostable film made from a 

blend of polylactic acid (PLA) and a bio-based polymer 

(PBAT). These films could eliminate “greenwashing” when an 

organization spends more time and money marketing itself as 

environmentally friendly than minimizing its environmental 

impact. PLA and PBAT are already used in biodegradable 

plastics such as waste bags. However, to make the films more 

suitable for packaging, Dehmoubed made them thicker and 

added certain proportions of different renewable elements 

to make them more sustainable. Now, their compostable 

film, called D42, is certified to degrade in home compost 

environments within one-hundred eighty days and industrial 

compost environments within ninety days. Dehmoubed claims 

that EcoPackables is the most sustainable packaging company 

because they have the highest proportion of renewable 

resources (organic materials) to PBAT while still breaking 

down into organic biomass, water, and CO 2 

, leaving behind 

zero plastic waste. “I’ve been very passionate about reducing 

BY SHERRY WANG 

plastic waste and stopping climate change. Specifically, how 

you can reduce your carbon footprints based on how you 

produce packaging material and handle proper end-of-life 

disposal,” Dehmoubed said. 

Historically, the packaging industry has been one of the 

most commoditized—no company owns more than five 

percent of the market share. For a younger entrepreneur like 

Dehmoubed, building a brand in such an environment was 

challenging. Thus, he built a brand focused on sustainability 

instead of being a direct competitor of packaging companies. 

He was not interested in cutting costs or taking shortcuts 

to increase the bottom line, or the company’s net profit, 

but rather wanted to hit the triple bottom line: good for the 

customer, good for the planet, and good for the company. His 

biggest challenge was selling his vision to traditionally archaic 

buyers hyper-focused on net profits. However, by convincing 

companies to look towards the younger generations for future 

sustainable operations, Ecopackables is being used by brands 

such as Ivory Ella, Beats, and Bud Light. 

Dehmoubed envisions that EcoPackables will become a 

globally recognized brand for its sustainable practices. He 

hopes to become a one-stop shop for brand-oriented companies 

looking to clean up their operations. Currently, they have two 

more products in the works: food-safe packaging developed 

using post-consumer recycled content and curbside recyclable 

Ocea brand polythene bags. The thin Ocea plastic bags are 

made from Forest Stewardship Council certified mixed paper, 

ensuring that products come from responsibly managed forests 

that provide environmental, social, and economic benefits. 

Ocea launched their product earlier this year to eliminate 

plastic from accumulating in our oceans. “Packaging is 

extremely important because it’s the first part of your product 

the customer interacts with. And we know how important first 

impressions are,” Dehmoubed said. ■ 

SHERVIN 

DEHMOUBED 

IMAGE COURTESY OF SHERVIN DEHMOUBED 


PHOTO COURTESY OF ALEX DONG 

TYLER MYERS 

Organic Chemistry is one of the most notoriously difficult 

classes at Yale. Pre-med hopefuls and chemistry whizzes 

alike spend long nights learning reaction mechanisms 

and drawing energy-level diagrams. But last year, one Yale teaching 

fellow (TF) went above and beyond by making Organic Chemistry 

a much more manageable, even enjoyable experience. Tyler Myers, 

a Chemistry Ph.D. candidate in the Miller Lab, is making an impact 

on his students through his palpable passion for chemistry. 

Myers discovered his love for the subject in high school, spending 

three years learning chemistry with a phenomenal teacher named Ms. 

Bell. His interest brought him to the University of Wyoming, where he 

was a chemistry major. After one of his general chemistry exams, his 

professor, David Anderson, passed him a note which read: Big-T, you 

should talk to me about research! “Research was completely foreign to 

me — but it was one of the best experiences I’ve ever had,” Myers said. 

In Anderson’s lab, Myers synthesized complexes to help construct 

hydrogen-based fuel cells. After taking Organic Chemistry with 

Robert Corcoran and loving it, Myers switched to Michael Taylor’s lab, 

where he worked on selective modifications of the amino acid residue 

tryptophan in peptides and proteins. 

The next stop for Myers was Yale—as a graduate student in Scott 

Miller’s lab. He remembers sitting in the airport before flying to New 

Haven for an admitted students visit when he saw that the Miller 

Lab had recently published a paper on the selective modification 

of Geldanamycin, a biologically active natural product. “Late-stage 

diversification of natural products was fascinating to me,” Myers 

said. While at Yale, he attended a meeting with Miller and heard 

more about his research. “All I remember was that my chest got 

really fuzzy,” Myers said, “I knew that this was the place for me.” 

Now, Myers researches asymmetric catalysis—working to 

preferentially synthesize one enantiomer of a chemical compound 

over the other. Enantiomers are chemical structures that are 

non-superimposable mirror images of each other, and it can 

be challenging to selectively synthesize one enantiomer of a 

compound. “The most common example we use is our hands,” 


GRADUATE PROFILE 

BY SOPHIA BURICK 

Myers said, “Just how you can write better with one hand, drugs 

experience a very similar phenomenon with biological activity, 

where one enantiomer of a drug is often more biologically active 

than the other.” Myers, now a third-year Ph.D. candidate, recently 

received the prestigious NSF Graduate Research Fellowship for his 

potential to contribute to the field of chemistry and broaden access 

to science and research. 

Myers is equally excellent in his work as a teaching fellow. As 

students in First-year Organic Chemistry, CHEM 174, last fall will tell 

you, Myers was a saving grace. He has loved teaching since he was 

an undergraduate, working as a tutor, a teaching assistant, and even 

traveling across Wyoming to deliver engaging scientific demonstrations 

to students to encourage them to pursue a STEM education. 

“I thought being a teaching fellow would be great practice since I 

want to go into academia, and it was another opportunity to interact 

with students. It was really fun. I met some phenomenal students that 

are really passionate,” Myers said. His work as a TF won him a Yale 

Prize Teaching Fellowship—one of the highest honors a graduate 

student at Yale can receive. He was nominated for the award by the 

many appreciative students in CHEM 174. “Tyler was a great TF and 

also such a great mentor. He encouraged me to pursue chemistry 

research and was a friendly face this summer when I was in a lab 

near his,” said Lizbeth Lozano, one of Myers’s past students. 

“I got to read the reviews that students wrote,” Myers said, 

“I remember leaving work just ecstatic.” Knowing his students 

truly enjoyed his work as a teaching fellow was the most 

rewarding thing for Myers. 

After graduating, Myers hopes to become a professor at a 

primarily undergraduate institution. His goal is to dismantle the 

reputation of organic chemistry as an intimidating, inaccessible 

science and help others appreciate the beauty and potential it holds. 

“I am fortunate to have so many great opportunities and supportive 

people in my life,” Myers said, “I think teaching at a primarily 

undergraduate institution would be an excellent opportunity to 

give back to the community.” ■ 


BY 

KELLY 

CHEN 

THE WORLDS WE 

DON'T REALIZE 

Close your eyes and take a deep breath. Imagine that you 

SCIENCE I N 

can suddenly hear the hum of two insects communicating, 

smell every scent trail, or even feel the Earth’s magnetic 

field. Supersonic hearing, enhanced smell, or an internal sense 

of direction—traits we think of as superpowers have long been 

possessed by animals. 


Join Ed Yong in his book An Immense World: How Animal Senses 

Reveal the Hidden Realms Around Us as he takes you on journeys 

you may literally never be able to see. For example, most animals 

can see ultraviolet (UV) light. With UV vision, rodents are better 

able to see birds in the sky, fish can easily identify plankton in 

water, and reindeer can comfortably find mosses and lichens to 

eat, all because of UV light detection. Yong’s curiosity will pull 

you in as he shows you discoveries made by scientists over the 

years, as well as his own encounters with the animal world; his 

easy-going language yet detailed imagery transports you right to 

the middle of other animals’ worlds while also teaching you about 

the science behind it all. 

As you dive into the book, you’ll learn about different Umwelts—a 

German term popularized by the Baltic-German zoologist Jakob 

von Uexküll—defined as “the part of [the animal’s] surroundings 

that an animal can sense and experience—its perceptual world.” 

Yong writes, “Nothing can sense everything, and nothing needs 

to.” From hearing about everything from snakes and elephants 

to mosquitoes and dogs, you'll realize that the sensory skill sets 

between animals are widely different, and for good reason. If we 

were to sense everything, Yong said, “[we] would be overwhelmed 

by the flood of stimuli, most of which would be irrelevant.” The 

things we perceive are special to our Umwelt with unnecessary 

information filtered from our senses as we evolve. 

And though we might wish for some of the senses other animals 

possess, human senses have advantages. For example, humans are 

one of the most visually adept species. While we may not be able 

to track scents with our noses, we are one of the best species at 

differentiating between scents. 

However, most of all, we have the technology to explore the 

Umwelts of the world. “This ability to dip into other Umwelten 

is our greatest sensory skill,” says Yong. Though we may never 

be able to truly experience the Umwelts of other animals, our 

growing knowledge enables us to understand and choose to see 

the world from realms that are not our own. By reading Yong’s 

engrossing novel, the world as we know it suddenly becomes 

much more vibrant. As Yong puts it, “It is not a blessing we 

have earned, but it is one we must cherish." ■ 


THE SKY IS FOR 

EVERYONE 

BY 

CELINA ZHAO 

The Sky is for Everyone: Women Astronomers in 

Their Own Words is a newly published collection of 

autobiographical excerpts from renowned women 

in astronomy, detailing their challenges and triumphs in this 

historically male-dominated field. It features two prominent 

Yale astrophysicists: Meg Urry, Israel Munson Professor of 

Physics and Director of the Yale Center for Astronomy and 

Astrophysics, and Priyamvada Natarajan, Joseph C. and Sofia 

C. Futon Professor of Astronomy and Physics and Director of 

Yale’s Franke Program in Science and the Humanities. 

In her chapter titled “The Gentlemen and Me,” Dr. Urry 

speaks about the few times this field felt unwelcoming. As one 

of two women in her graduate astronomy program, she was 

never invited to weekly study sessions and was cruelly pranked 

with a Playgirl magazine by her male classmates. Dr. Natarajan’s 

chapter focuses on her background, work, and personal journey 

through academia and how her love for science developed. 

What was your reaction when asked to contribute to this book? 

Urry: I actually told them I couldn’t do it at first, but then 

shortly after Covid hit, while I was sitting at home, I was 

reflecting about where I was and how I’d gotten there and 

thought, “Wow, this is really something I’d like to do.” 

Natarajan: I was very honored but also kind of surprised 

and intrigued because they made it explicit that they wanted 

something about my personal experience and journey, and I didn’t 

think that would be something of interest. 

What was your writing process? 

Urry: In two days, I’d actually written eighteen thousand 

words while the editors had only wanted three thousand. So, I 

spent time cutting it down—the whole process actually inspired 

T H E 

SPOTLIGHT 

me to write and tell more of my stories. 

Natarajan: I like writing, and I do a lot of different kinds of it, 

but it was very challenging because I don’t ever write explicitly 

about myself… It was also interesting to go over my path and 

look back—I tend not to reminisce much as there is so much 

more science that I want to do. 

Why do you think these stories are important? 

Urry: Sadly, I think it’s because there hasn’t been enough 

change. When I came to Yale in 2001, I was the only woman in 

the physics department faculty. Now we have six so there’s been 

Professor Urry next to her book. 

PHOTO COURTESY OF JENNY WONG 

a positive change there, but I still hear younger women talking 

about similar experiences [that I talk about in the book]. 

Natarajan: It was quite amazing to hear about how others 

had found their way into academia and what motivates them. 

It’s so important for people to see that there’s no one way to 

be a scientist…. But what’s really sobering is that you can see 

that a lot of women have had more challenging paths through 

intellectual life [than men], and it’s important to see all the 

different kinds of struggles and how they persevered for the 

love of the subject. ■ 



IMAGE COURTESY OF NIH PHOTO LIBRARY 

COUNTERPOINT 

A New Way of 

Detecting Alzheimer’s 

BY ABIGAIL JOLTEUS 

Imagine progressively losing the memories you 

cherish deeply, eventually no longer being able 

to learn new things, read and write with ease, 

or recognize loved ones. People with Alzheimer’s, a 

form of dementia, lead lives with these worsening 

symptoms. With no cure and a short lifespan after 

diagnosis, Alzheimer’s is a devastating, progressive 

neurological disorder that affects memory, behavior, 

motor skills and thought processes. 

Initially, scientists could only diagnose Alzheimer’s 

by performing an autopsy after death. Since then, 

many advances have been made. Clinicians can now 

detect early signs using remarkable technology, such 

as positron emission tomography (PET), a type of diagnostic 

technology used to show the metabolic activity 

of the brain, and various tests on cerebrospinal fluid 

(CSF)—the clear, watery fluid around the spinal cord 

and brain. Some hallmarks include decreased glucose 

uptake and the accumulation of beta-amyloid plaques, 

proteins that aggregate between neurons and disrupt 

their normal function. However, these methods can be 

quite invasive. For example, a PET scan requires the 

injection of radioactive material into the bloodstream, 

and the extraction of CSF involves inserting a needle 

into someone’s back. These diagnostic tools are uncomfortable 

and expensive, making these procedures 

inaccessible to many people. 

Alzheimer’s is characterized by plaques of beta-amyloid 

in the brain, yet new evidence suggests these 

plaques also accumulate in the retina. The retina, which 

is closely related to brain tissue, is routinely examined 

to detect eye diseases through a process called fundus 

photography or digital retinal imaging. A similar technique 

may soon provide a non-invasive and cost-efficient 

method of identifying early signs of Alzheimer’s. 

Robert Vince, Swati More, and their colleagues at 

the University of Minnesota discovered a technique 

called hyperspectral imaging. They used the technique 

to detect clumps of beta-amyloid in mouse retinas 

at the early stages of the disease. In hyperspectral 

imaging, standard eye examination equipment, like 

an autorefractor, is combined with a hyperspectral 

camera — a special camera that captures light from 

IMAGE COURTESY OF EMMAGARCIAMILLER 

across the electromagnetic spectrum. 

Then, artificial intelligence compares 

the data-rich images with other images 

with similar physical properties associated 

with Alzheimer’s disease. 

Clinical trials are currently underway 

across North America to test the efficacy of this technique, 

and there have already been promising results. 

In a cohort of 108 participants who were either at risk 

of Alzheimer’s or already had preclinical Alzheimer’s, 

the technique correctly identified people with beta-amyloid 

plaques in their brains eighty-six percent 

of the time. PET scans and CSF results validated these 

retinal screening tests. They also observed beta-amyloid 

clumps in the brain at later stages, suggesting that 

the presence of beta-amyloid plaques in 

the retina may also be an early detection 

marker in humans. 

Though these results are promising, 

more studies with diverse participants 

and larger cohorts are needed before phy- sicians 

can use this technique as an official diagnostic tool. 

Moreover, some researchers have noted that amyloids 

can be present in the retinas of people that do 

not develop signs of cognitive decline. 

While there are issues with this technique that 

need to be resolved, early detection of 

Alzheimer’s using retinal imaging has the 

potential to become a widely-used diagnostic 

tool. Other retinal signs may 

help with the early detection of Alzheimer’s, 

including retinal thickness and changes 

in blood vessels. A longitudinal trial called Atlas of 

Retinal Imaging in Alzheimer’s Study (ARIAS) is 

examining these retina-based biomarkers in hopes 

of improving the early diagnosis of Alzheimer’s. 

This project is still in the recruiting phase, but if 

proven successful, researchers may seek to develop 

more types of retinal-based tests. Earlier treatment 

of Alzheimer’s may alleviate many 

symptoms and help scientists better understand 

the pathogenesis of this condition 

with the hope of developing a cure. ■ 


HIDDEN 

HISTORIES 

BESTIE BLOUNT GRIFFIN 

BY ILORA ROY 

ART BY NOORA SAID 

Bessie Blount Griffin was an inventor, nurse, physical 

therapist, forensic handwriting and document analyst, 

and avid public speaker. However, unlike many in her 

field, she was Black, left-handed, and a woman. Blount was born 

on November 24, 1914, in Hickory, now Chesapeake, Virginia, 

to parents George Woodard and Mary Elizabeth Griffin. In 

elementary school, her teachers constantly reprimanded her 

for writing with her left hand. After having her knuckles 

rapped countless times, Blount protested: if it was wrong for 

her to write with her left hand, then it must also be wrong to 

write with her right! She then taught herself how to write with 

her teeth and toes in response to her teacher’s disapproval. 

Blount studied nursing at Keney Memorial Hospital and 

physical therapy at Union Junior College and Panzer College 

of Physical Education and Hygiene. After obtaining her degree 

from Union, Blount became a licensed physiotherapist at the 

Bronx Hospital in New York, where she helped World War 

II veterans with amputated limbs. She was not your average 

nurse. In addition to supporting amputee patients in recovering 

their balance and mobility, she also helped them reclaim their 

independence. Blount took a page out of her own book and 

taught the veterans how to write with their teeth and toes. 

“You’re not crippled, only crippled in your mind,” she said. 

She continued to look for ways to give veterans autonomy 

over their bodies, for example, inventing a device called the 

Invalid Feeder to help. Patients would bite down on a tube that 

would activate a motor, and food would dispense through a 

mouthpiece in the shape of a spoon. The device shuts off after 

each cycle to ensure the patient would not choke. While Blount 

continued to work as a nurse during the day, she would work 

late hours in the night from 1:00 AM to 4:00 AM building her 

instruments. Blount did not have a degree in engineering, yet 

she was able to construct ingenious devices because of her 

passion for helping patients. 

Continuing to invent, Blount created more apparatuses, such 

as disposable kidney-shaped basins to dispose of bodily waste 

and the “portable receptacle support,” similar to the “invalid 

feeder,” with the addition of a neck brace with a bowl. The 

latter received a patent under her name on April 24, 1951, 

making Blount one of the first officially recognized inventors 

in physical therapy. She had many other accomplishments 

from becoming a handwriting analyst for several police 

departments— including Scotland Yard in England, where she 

was the first Black American woman to have trained there—to 

starting her own consulting business in her hometown. 

However, Blount’s accomplishments did not come without 

challenges. After inventing the “invalid feeder,” she wanted to 

bring relief to others around the country, but the US military 

refused to pay Blount a fair amount. She also tried to sell her 

devices to the American Veterans Association, but they did not 

want to support her due to her race and gender. Blount wanted 

to prove that her inventions 

themselves were impressive 

and did not want to tie 

her inventions to her 

identity as a Black 

woman. She was 

not driven 

by financial 

motivation 

but rather by 

the idea of 

helping society 

progress 

through her 

innovations. 

Even after being 

turned down 

by many different 

organizations, she 

eventually donated the 

“invalid feeder” to France, 

where the French 

used it in military 

hospitals. Belgium 

also bought 

her disposable 

basins. ■ 



AD_Yale_SC_ENG_half_FALL_10_19qxp.qxp_8 10/7/19 12:05 PM Page 1 

Welcome to Yale! 

The Yale Science and Engineering 

Association is here for you. 

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

organizations in the world with a focus on STEM. 

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

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

engineering community. 

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

supporting you at Yale and beyond! 

Join us at: ysea.org

YSM Issue 95.3

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