YSM Issue 96.3
Yale Scientific THE NATION’S OLDEST COLLEGE SCIENCE PUBLICATION • ESTABLISHED IN 1894 SEPTEMBER 2023 VOL. 96 NO. 3 • $6.99 KEEP AN EYE ON IT 16 MEET MOIRÉ MATERIALS 12 THAT MAGNETIC TOUCH 14 COVID-19 NASAL SPRAY 19 VENUS’ SKINCARE ROUTINE 22
- Page 2 and 3: TABLE OF VOL. 96 ISSUE NO. 3 COVER
- Page 4 and 5: & By Ximena Leyva Peralta MODERN-DA
- Page 6 and 7: NEWS Physics / Medicine TOO STRANGE
- Page 8 and 9: FOCUS Artificial Intelligence DEEP
- Page 10 and 11: FOCUS Computer Science REPRESENTATI
- Page 12 and 13: FOCUS Electrical Engineering WHY TI
- Page 14 and 15: FOCUS Planetary Sciences THAT MAGNE
- Page 16 and 17: FOCUS Ophthalmology KEEP AN EYE ON
- Page 18 and 19: FOCUS Ophthalmology happen when mel
- Page 20 and 21: FOCUS Biomedical Engineering Corona
- Page 22 and 23: FOCUS Astronomy Computational Biolo
- Page 24 and 25: FOCUS Astronomy findings to the rel
- Page 26 and 27: FEATURE Archaeology THE BRICK OF LI
- Page 28 and 29: FEATURE Physics THE PHONON PHENOMEN
- Page 30 and 31: FEATURE Geochemistry BARNACLE BREAD
- Page 32 and 33: FEATURE Astrophysics TWINKLE, TWINK
- Page 34 and 35: UNDERGRADUATE PROFILE HARPER LOWREY
- Page 36 and 37: WRITING FOR THEIR LIVES BY KEYA BAJ
- Page 38 and 39: POINT The Discovery of a Superheavy
- Page 40: Interested in getting involved with
Yale Scientific<br />
THE NATION’S OLDEST COLLEGE SCIENCE PUBLICATION • ESTABLISHED IN 1894<br />
SEPTEMBER 2023<br />
VOL. 96 NO. 3 • $6.99<br />
KEEP AN EYE<br />
ON IT 16<br />
MEET MOIRÉ MATERIALS 12<br />
THAT MAGNETIC TOUCH 14<br />
COVID-19 NASAL SPRAY<br />
19<br />
VENUS’ SKINCARE ROUTINE 22
TABLE OF<br />
VOL. 96 ISSUE NO. 3<br />
COVER<br />
16<br />
A R T<br />
I C L E<br />
Keep An Eye On It<br />
Johnny Yue & Risha Chakraborty<br />
Yale scientists have uncovered more about the mechanisms of age-related macular degeneration<br />
(AMD), one of the leading causes of vision loss worldwide. From discovering possible therapeutic<br />
targets for AMD and other neurodegenerative diseases to uncovering a quantum chemistry<br />
reaction in the retina, their findings could not only inform potential AMD treatments, but also<br />
offer applications beyond the eye.<br />
12 Meet Moiré Materials<br />
William Archacki<br />
The newly fabricated ‘moiré materials’ are poised to overhaul light-sensing electronics at an atomic<br />
level. But how do they work? Yale researchers dove into the quantum world and put their own<br />
twist on the classic moiré effect recipe.<br />
14 That Magnetic Touch<br />
Elizabeth Watson<br />
The reason why certain meteorites can generate magnetic fields has puzzled the scientific<br />
community for years. Two Yale researchers propose an answer: collisions between asteroids give<br />
way to magnetic meteorites. Their new study advances our understanding of asteroids and the<br />
formation of magnetic dynamos at planetary cores, with potential implications for the upcoming<br />
NASA mission dubbed ‘Psyche.’<br />
19 COVID-19 Nasal Spray<br />
Evelyn Jiang<br />
Current mRNA vaccines, injected into the upper arm, excel at activating immune defenses in the<br />
bloodstream, but are not as effective at rallying protective responses in the upper airway and lungs. A<br />
team of Yale scientists made major advancements towards developing an mRNA nasal spray vaccine<br />
using nanoparticles that would offer a geographical advantage when it comes to targeting viral<br />
respiratory illnesses like COVID-19.<br />
21 Venus' Skincare Routine<br />
Cindy Mei & David Gaetano<br />
The surface of Venus has been observed to be less than a billion years old, which is much younger than<br />
its known age of 4.5 billion years. Scientists from Yale and the Southwest Research Institute showed that<br />
high-velocity collision events that happened in the early period of planet formation caused prolonged<br />
volcanic activity on Venus, leading to resurfacing that gives the planet its youthful appearance.<br />
2 Yale Scientific Magazine September 2023 www.yalescientific.org
CONTENTS<br />
More articles online at www.yalescientific.org & https://medium.com/the-scope-yale-scientific-magazines-online-blog<br />
4<br />
6<br />
25<br />
34<br />
Q&A<br />
NEWS<br />
FEATURES<br />
SPECIALS<br />
Can AI Determine the Scent of a Compound Based On Its<br />
Chemical Structure? • Ximena Leyva Peralta<br />
Modern-Day Trephination • Andrea Ortega<br />
Strange Metals • Proud Ua-arak<br />
Promising New Drug to Combat Resistant HIV • Sofia Arbelaez<br />
It's All In The Stones • Patrick Wahlig<br />
Happy Spouse, Happy House • Sunny Vuong<br />
Deep Learning • Sophia Burick<br />
Cancer: Not Just Bad Luck? • Sebastian Reyes<br />
Capturing the Physics of Afro-Textured Hair • Abigail Jolteus<br />
Super-Sizing Life's Smallest Secrets • Kara Tao<br />
Teeny Tiny Droplet Batteries • Sharna Saha<br />
The Brick of Life • Ilora Roy<br />
Scent-sational Memory Boost • Kenny Cheng<br />
Harnessing Atomic Breaths • Annli Zhu & Lea Papa<br />
Barnacle Breadcrumbs • Madeleine Popofsky<br />
Twinkle, Twinkle, Giant Star • Diya Naik & Robin Tsai<br />
Undergraduate Profile: Harper Lowrey (YC '24) • Nyla Marcott<br />
Alumni Profile: Ilana Yurkiewicz (YC '10) • Himani Pattisami<br />
Science in the Spotlight: Writing For Their Lives • Keya Bajaj<br />
Science in the Spotlight: Racism in Health • Samuel Obiama<br />
Counterpoint: The Heaviest Air in the World • Ian Gill<br />
Perimeter • Isaiah Asbed<br />
www.yalescientific.org<br />
September 2023 Yale Scientific Magazine 3
&<br />
By Ximena Leyva Peralta<br />
MODERN-DAY TREPHINATION:<br />
HOW DO YOU SAFELY<br />
INSERT AN ELECTRODE<br />
INTO THE BRAIN?<br />
By Andrea Ortega<br />
In 6,000 B.C.E., North African physicians treated head ailments<br />
with trephination—the practice of drilling holes into patients’<br />
skulls without anesthesia. Luckily, modern-day trepanning is much<br />
less invasive. A research team in Geneva, Switzerland is employing<br />
flexible, biocompatible materials in electrocorticography (ECoG), the<br />
monitoring of electrical activity associated with the brain. Normally, to<br />
detect the brain’s signals, neurosurgeons must carve out a ten-squarecentimeter<br />
section of the skull and insert electrodes through the hole,<br />
positioning them on the surface of the cerebral cortex. By creating a<br />
new soft, deployable ECoG system, the team has revolutionized neural<br />
recording by minimizing risks of infection and brain damage that<br />
accompany the removal of a large section of the skull.<br />
The novel soft ECoG system is composed of six spiral-shaped, folded<br />
arms that form a cylindrical “electrode array,” which extends through<br />
a one-square-centimeter incision in the skull. The system works by<br />
administering fluidic pressure into each arm, causing the arms to slowly<br />
expand within the one-millimeter space between the skull and the<br />
brain’s surface. Each component of the array is embedded with strain<br />
sensors, which monitor the deployment of the soft arms and tell the user<br />
when to stop applying pressure.<br />
In an in vivo experiment performed on a miniature pig, the soft<br />
robotic electrodes yielded successful readings of sensory activity<br />
and did not cause any structural damage. Thus, ECoG could play a<br />
large role in mapping regions of the brain associated with epilepsy,<br />
recording the brain’s functions, and controlling the movement of<br />
prosthetic limbs. Further advances are still necessary, but soft robotics<br />
demonstrate extraordinary capabilities in laying the groundwork for<br />
these advancements. ■<br />
CAN AI DETERMINE THE<br />
SCENT OF A COMPOUND<br />
BASED ON ITS CHEMICAL<br />
STRUCTURE?<br />
Scientists have long known that the chemical structure of a<br />
molecule influences its smell. However, it’s still unclear how<br />
tiny structural changes in a molecule’s structure can turn a<br />
sweet, delicate scent into a fishy stench.<br />
Enter artificial intelligence (AI). Researchers from the startup<br />
Osmo based in Cambridge, Massachusetts trained a type<br />
of AI system called a neural network to predict a compound’s<br />
odor based on its structure. The scientists instructed the system<br />
to assign descriptors from a list of fifty-five, such as “grassy” or<br />
“fruity,” to a scent. The AI system then generated an odor map by<br />
screening roughly five thousand well-studied molecules.<br />
To test the validity of this map, a panel of fifteen trained study<br />
participants sniffed a set of compounds with undocumented<br />
scents. Their answers were averaged to account for genetic<br />
differences, personal experiences, and preferences. The<br />
researchers found that the AI system achieved results comparable<br />
to the human assessments for fifty-three percent of the molecules.<br />
This new odor map could be a helpful reference tool when<br />
designing new scents in the food or perfume industries. But<br />
it doesn’t seem to reveal much about how humans interpret<br />
smell. Odor descriptors are quite subjective, and it’s unclear if<br />
averaging the answers of a group of people is the best way to<br />
obtain Aa “correct” description of a smell.<br />
Most smells in the real world come from a mixture of<br />
compounds. The next frontier for the AI system may be to<br />
chemically describe the complex smoky smell of freshly brewed<br />
coffee or the aromatic sweetness of a new perfume. ■<br />
4 Yale Scientific Magazine September 2023 www.yalescientific.org
The Editor-in-Chief Speaks<br />
PAST, PRESENT, AND FUTURE<br />
Often, scientific advances don’t involve the creation of never-before-seen<br />
technologies or completely novel theories; instead, scientists apply previous<br />
research in unconventional ways, bringing together disparate fields in search<br />
of new discoveries. What “innovation” or “advancement” means to each team of<br />
researchers will vary, but if you look closely, most are the product of collaboration<br />
across disciplines.<br />
In this issue, we highlight several of these developments made possible by<br />
interdisciplinary inspiration, and explore how they may propel their respective<br />
fields into the future. Our cover story features two groups at the Yale School of<br />
Medicine who have uncovered more about the mechanisms of age-related macular<br />
degeneration—one of the leading causes of blindness in the world—through the<br />
seemingly unrelated lenses of neurodegeneration and quantum chemistry (pg. 16).<br />
In another article, we recount a geochemist’s resourceful use of barnacle shells to<br />
decode the ocean path of lost Malaysian Airlines Flight MH370, whose final resting<br />
place has not been uncovered since the plane vanished in 2014 (pg. 30).<br />
Just as important as looking to the future is carefully studying the past—whether<br />
for inspiration, for wisdom, or for guidance. This issue’s alumni profile features Dr.<br />
Ilana Yurkiewicz (YC ’10), who, thirteen years ago, was in my very position writing<br />
to you as the Editor-in-Chief of the Yale Scientific. She has since gone on to become<br />
an incredibly successful physician-writer, and continues to serve as a role model<br />
not just for myself, but for everyone at <strong>YSM</strong> (pg. 35). One of our Science in the<br />
Spotlight articles takes us back even further—nearly a century back—to highlight<br />
the untold stories of Jane Stafford and other pioneering female science journalists<br />
who overcame all odds in the male-dominated industry to leave an enduring legacy<br />
that is still felt today (pg. 36).<br />
Speaking of the present, the Yale Scientific itself has been undergoing a few<br />
changes. The <strong>YSM</strong> offices in Welch Hall and 305 Crown St. were, despite our best<br />
efforts, repurposed by the Yale College Dean’s Office this past summer, so we have<br />
worked tirelessly to find new storage spaces for our collection of magazines dating<br />
back to the 19 th century. In September, I established a permanent installation of<br />
our <strong>YSM</strong> archives in the Benjamin Franklin college library, which presents a nearcomprehensive<br />
display of our historical issues that is accessible to any interested<br />
students, staff, faculty, and alumni. I would like to extend a special thanks to<br />
Professor Jordan Peccia, Head of Benjamin Franklin College, and Maria Bouffard<br />
for their time and generosity in making this timeless installation possible.<br />
Finally, I would like to thank our contributors, masthead, advisors, and readers<br />
who have continued to support our mission of accessible science communication<br />
throughout the years. Here’s to the generations of those who came before us, and to<br />
those who have yet to come.<br />
About the Art<br />
Alex Dong, Editor-in-Chief<br />
This cover illustration depicts researchers<br />
zooming into the retina and investigating the<br />
macula through machine learning methods.<br />
Catherine Kwon, Cover Artist<br />
MASTHEAD<br />
September 2023 VOL. 96 NO. 3<br />
EDITORIAL BOARD<br />
Editor-in-Chief<br />
Managing Editors<br />
News Editor<br />
Features Editor<br />
Special Sections Editor<br />
Articles Editor<br />
Online Editors<br />
Copy Editors<br />
Scope Editors<br />
PRODUCTION & DESIGN<br />
Production Manager<br />
Layout Editors<br />
Art Editor<br />
Cover Artist<br />
Photography Editor<br />
BUSINESS<br />
Co-Publishers<br />
Operations Manager<br />
Subscriptions Manager<br />
Outreach Manager<br />
OUTREACH<br />
Synapse Presidents<br />
Synapse Vice President<br />
Synapse Outreach Coordinators<br />
Synapse Events Coordinator<br />
WEB<br />
Web Managers<br />
Head of Social Media<br />
Social Media Coordinators<br />
STAFF<br />
Sanya Abbasey<br />
Luna Aguilar<br />
Ricardo Ahumada<br />
William Archacki<br />
Dinesh Bojja<br />
Risha Chakraborty<br />
Kelly Chen<br />
Leah Dayan<br />
Steven Dong<br />
Chris Esneault<br />
Erin Foley<br />
Mia Gawith<br />
Simona Hausleitner<br />
Tamasen Hayward<br />
Katherine He<br />
Miriam Huerta<br />
Sofia Jacobson<br />
Jenna Kim<br />
Catherine Kwon<br />
Charlotte Leakey<br />
Ximena Levya Peralta<br />
Yurou Liu<br />
Samantha Liu<br />
Helena Lyng-Olsen<br />
Kaley Mafong<br />
Georgio Maroun<br />
Cindy Mei<br />
Lee Ngatia Muita<br />
Lea Papa<br />
Hiren Parekh<br />
Himani Pattisam<br />
Emily Poag<br />
Madeleine Popofsky<br />
Tony Potchernikov<br />
Zara Ranglin<br />
Yusuf Rasheed<br />
Alex Roseman<br />
Ilora Roy<br />
Ignacio Ruiz-Sanchez<br />
Noora Said<br />
Alex Dong<br />
Madison Houck<br />
Sophia Li<br />
Sophia Burick<br />
Anavi Uppal<br />
Hannah Han<br />
Kayla Yup<br />
Krishna Dasari<br />
Mia Gawith<br />
William Archacki<br />
Matthew Blair<br />
Jamie Seu<br />
Samantha Liu<br />
Anya Razmi<br />
Malia Kuo<br />
Madeleine Popofsky<br />
Sydney Scott<br />
Kara Tao<br />
Catherine Kwon<br />
Jenny Wong<br />
Lucas Loman<br />
Dinara Bolat<br />
Tori Sodeinde<br />
Georgio Maroun<br />
Yusuf Rasheed<br />
Hannah Barsouk<br />
Sofia Jacobson<br />
Jessica Le<br />
Kaley Mafong<br />
Lawrence Zhao<br />
Anjali Dhanekula<br />
Abigail Jolteus<br />
Emily Shang<br />
Elizabeth Watson<br />
Keya Bajaj<br />
Eunsoo Hyun<br />
Jamie Seu<br />
Kiera Suh<br />
Yamato Takabe<br />
Joey Tan<br />
Kara Tao<br />
Connie Tian<br />
Van Anh Tran<br />
Sheel Trivedi<br />
Robin Tsai<br />
Sherry Wang<br />
Elise Wilkins<br />
Aiden Wright<br />
Elizabeth Wu<br />
Nathan Wu<br />
Johnny Yue<br />
Iffat Zarif<br />
Hanwen Zhang<br />
Lawrence Zhao<br />
Celina Zhao<br />
Matthew Zoerb<br />
The Yale Scientific Magazine (<strong>YSM</strong>) is published four times a year by Yale<br />
Scientific Publications, Inc. Third class postage paid in New Haven, CT<br />
06520. Non-profit postage permit number 01106 paid for May 19, 1927<br />
under the act of August 1912. ISN:0091-287. We reserve the right to edit<br />
any submissions, solicited or unsolicited, for publication. This magazine is<br />
published by Yale College students, and Yale University is not responsible<br />
for its contents. Perspectives expressed by authors do not necessarily reflect<br />
the opinions of <strong>YSM</strong>. We retain the right to reprint contributions, both text<br />
and graphics, in future issues as well as a non-exclusive right to reproduce<br />
these in electronic form. The <strong>YSM</strong> welcomes comments and feedback. Letters<br />
to the editor should be under two hundred words and should include the<br />
author’s name and contact information. We reserve the right to edit letters<br />
before publication. Please send questions and comments to yalescientific@<br />
yale.edu. Special thanks to the Yale Science and Engineering Association.
NEWS<br />
Physics / Medicine<br />
TOO STRANGE<br />
TO BE TRUE?<br />
A RACE AGAINST<br />
RESISTANCE<br />
THE CHOREOGRAPHY OF<br />
STRANGE METALS<br />
PROMISING NEW DRUG TO<br />
COMBAT RESISTANT HIV<br />
BY PROUD UA-ARAK<br />
BY SOFIA ARBELAEZ<br />
IMAGE COURTESY OF MARTIN DE ARRIBA<br />
IMAGE COURTESY OF KAROLINA GRABOWSKA<br />
The concept of electrons may have first been<br />
introduced in our chemistry classes with neat, easyto-follow<br />
Bohr models. But what happens when they<br />
don’t act the way scientists anticipate? Graduate student<br />
Kirsty Scott and Professor Eduardo H. da Silva Neto from<br />
the Yale Department of Physics set out to discover the<br />
nature of these so-called “strange metals.”<br />
According to basic quantum mechanics, an electron can<br />
be described as a quantum mechanical wave. “But in the<br />
strange metal phase, the wave description seems to not be<br />
applicable, which leaves us in a position where even the<br />
most advanced theories don’t seem able to explain what’s<br />
going on,” da Silva Neto said.<br />
The researchers were determined to uncover what<br />
happens at the electron level within these metals. Using<br />
a method called resonant inelastic X-ray scattering, they<br />
found a ‘quasi-circular’ pattern in the way electrons scatter<br />
at low energies. This means that when an electron changes<br />
direction while moving, it is free to change to any direction.<br />
‘Quasi-circular’ patterns have typically been assumed to be<br />
necessary for strange metals, but have not, until now, been<br />
directly measured.<br />
Matter matters. Scott, the leader of this study, believes that<br />
knowledge of the materials we use shapes our technology<br />
and therefore the society around us, as evidenced by<br />
historical periods like the “Stone Age” and the “Bronze<br />
Age” being defined by the materials of their time. Scott<br />
is enthusiastic about being part of a scientific endeavor<br />
where the study of novel material behaviors could usher in<br />
society’s next epoch. ■<br />
Yale physician Onyema Ogbuagu has been involved in<br />
clinical trials for HIV for more than a decade. Trained<br />
as a medical student in Nigeria during the peak of<br />
the HIV epidemic there, Ogbuagu has seen HIV treatment<br />
evolve considerably over the course of his career. “At the time<br />
[I was trained], reversing immune deficiency was a dream,”<br />
Ogbuagu said. Nowadays, directly managing HIV is a real<br />
option. However, multidrug resistance and therapeutic regimen<br />
complexity remain important barriers to treatment.<br />
Ogbuagu published a landmark phase-three clinical trial testing<br />
the effectiveness of Lenacapavir, a recently FDA-approved HIV<br />
treatment. Administered as a biannual injection, Lenacapavir is<br />
the longest-acting antiviral agent that has been approved for HIV<br />
treatment. As an antiretroviral therapy, Lenacapavir interrupts<br />
viral replication of HIV in the body, slowing the progression of<br />
the disease, improving immune function, and reducing the risk<br />
of HIV transmission. The treatment is of particular interest for<br />
patients demonstrating multidrug resistance.<br />
Lenacapavir contributed to a virologic suppression rate of over<br />
eighty percent, much higher than the average virologic suppression<br />
rates observed in other multidrug-resistant trials. “[The trial]<br />
holds promise that we’re able to reach certain people that wouldn’t<br />
be successfully treated with [other] regimens,” Ogbuagu said.<br />
As this medication is being tested to treat HIV, Ogbuagu<br />
is also hopeful that HIV treatment options may evolve into a<br />
wide range of different methods and frequencies of delivery.<br />
“People could have the luxury of choosing a method that’s<br />
effective and that fits their lifestyle and their preferences,” he<br />
said. Ogbuagu’s study certainly brings his hopes of creating<br />
simpler, more effective therapeutic regimens to improve<br />
quality of life closer to reality. ■<br />
6 Yale Scientific Magazine September 2023 www.yalescientific.org
Ecology / Public Health<br />
NEWS<br />
IT’S ALL IN<br />
THE STONES<br />
HAPPY SPOUSE,<br />
HAPPY HOUSE<br />
RIVER EROSION KEY TO<br />
FISH BIODIVERSITY<br />
BY PATRICK WAHLIG<br />
MARITAL STRESS ASSOCIATED<br />
WITH WORSE HEART<br />
ATTACK RECOVERY<br />
BY SUNNY VUONG<br />
IMAGE COURTESY OF ISAAC SZABO<br />
IMAGE COURTESY OF TIMUR WEBER<br />
A<br />
tiny, three-inch fish might hold the key to unlocking<br />
an ancient secret of evolution.<br />
Tucked away in the southern Appalachian Mountains<br />
is the Greenfin Darter (Nothonotus chlorobranchius), a hardy fish<br />
that exhibits tremendous genetic diversity. Until recently, the<br />
driver of this diversity was unknown. Researcher Maya Stokes,<br />
along with Yale Professor Thomas Near and a team of dedicated<br />
scientists, set out to discover the mechanism behind what appears<br />
to be real-time allopatric speciation, or speciation prompted by<br />
geographic isolation, in the Appalachian Mountains.<br />
Near puts the overall research question simply. “Why are<br />
we seeing species richness within the rivers themselves?” he<br />
said. The answer lies in the stones—erosion, to be exact.<br />
The Greenfin Darter is selective of its habitat, preferring<br />
hard metamorphic rock over soft sedimentary rock.<br />
Erosional processes in the Tennessee River, however, have<br />
exposed areas of sedimentary rock, separating regions<br />
of metamorphic rock. This has forced Greenfin Darter<br />
populations into isolation. The team’s research displays that<br />
erosion of metamorphic rock has severely reduced gene flow<br />
between populations of N. chlorobranchius, driving genetic<br />
divergence up. This research—an intersection between the<br />
fields of ichthyology (the study of fishes) and geoscience—<br />
has allowed a novel explanation of species divergence in what<br />
Near calls “geologically quiet” areas without tectonic influence.<br />
Stokes is thrilled with the recent work. “We tried to<br />
quantitatively combine data sets across disciplines,” she said.<br />
“We were able to integrate these datasets fairly seamlessly,<br />
which allowed us to highlight a novel geologic mechanism.”<br />
As research endeavors become increasingly integrative, this<br />
study is an inspiring example of interdisciplinary success. ■<br />
Heartbreak is purely figurative, referring to the sadness<br />
over a loved one wounding our emotional state, not<br />
our biological heart. However, a new study from<br />
researchers at the Yale School of Public Health indicates that<br />
the concept can become literal—at least, for those married<br />
or in a committed relationship. The study found that among<br />
1,593 adults who were treated for a heart attack, there was<br />
an independent association between severe marital stress<br />
and worse recovery through their first year after hospital<br />
discharge. This association was strong even after adjusting<br />
for patient demographics.<br />
The authors of the study, doctoral graduate Cenjing Zhu<br />
and Professor of Epidemiology Judith Lichtman, found that<br />
when following up after a year on symptoms reported by<br />
patients such as depression, chest pain, and overall quality of<br />
life, a strong association with marital stress still appeared in<br />
every aspect of their recovery.<br />
To the researchers, this calls attention to a need for<br />
better awareness that marital stress and other factors in the<br />
psychosocial domain could be important factors during the<br />
recovery process. “We absolutely have to think about all of<br />
the acute care, but we also have to broaden our perspective<br />
to think about other aspects that may be contributing to how<br />
well somebody recovers,” Lichtman said.<br />
“From a care provider perspective, there should be more<br />
prompting during their day-to-day communications with<br />
their patients about how they’re doing.” Zhu said. “It’s not<br />
only about numbers in the clinical factors, but also their<br />
overall well-being.” The study emphasizes the overlooked<br />
importance of overall social and mental well-being on<br />
physical recovery. ■<br />
www.yalescientific.org<br />
September 2023 Yale Scientific Magazine 7
FOCUS<br />
Artificial Intelligence<br />
DEEP<br />
LEARNING<br />
An Unexpected<br />
Tool To Fight<br />
Heart Valve Disease<br />
BY SOPHIA BURICK<br />
PHOTOGRAPH COURTESY OF CAROLINE BUCKY<br />
Severe aortic stenosis (AS) is a common form of valvular heart<br />
disease that involves the aortic valve becoming unusually<br />
narrow, affecting five percent of people above the age of<br />
sixty-five. Early diagnosis is essential to successful intervention.<br />
Usually, AS is detected through Doppler echocardiography, or<br />
ultrasound imaging of the heart. However, performing Doppler<br />
echocardiography requires access to specialized equipment as well<br />
as professionals who know how to operate the equipment and<br />
interpret the results. This discrepancy between the large population<br />
of individuals at risk for AS and the small amount of resources<br />
available for its diagnosis makes it difficult to achieve early diagnosis<br />
of AS, negatively impacting patient outcomes.<br />
Researchers at the Cardiovascular Data Science (CarDS) Lab at<br />
Yale recently published in European Heart Journal a creative new<br />
approach to making AS diagnostic tools more accessible—combining<br />
deep learning with simple ultrasound scans. Handheld devices that<br />
use ultrasound imaging to visualize the heart are much more widely<br />
available than the equipment necessary for Doppler echocardiography,<br />
but the images and videos alone produced by these ultrasound scans<br />
are difficult to use to diagnose AS. “Patients are often not seen by a<br />
cardiologist until they are very late in their disease stage,” Evangelos<br />
Oikonomou, a postdoctoral fellow in the CarDS Lab, said. “There’s a big<br />
opportunity to diagnose the disease earlier in this patient population.”<br />
The researchers at the CarDS Lab developed a novel deep learning<br />
model that is capable of using 2D echocardiograms, which are produced<br />
by simple ultrasound imaging, to identify AS without specialized<br />
Doppler equipment. Deep learning is a kind of machine learning<br />
that employs computer networks built to resemble human neural<br />
networks—in short, it teaches computers how to learn like humans.<br />
“You train the algorithm by showing it multiple different images<br />
and giving feedback to the algorithm as to whether its prediction<br />
[about what the image is] is correct or wrong,” Oikonomou said.<br />
“What the algorithm does is every time it gets [its prediction] wrong,<br />
it tries to adjust its approach and learn something from its errors.”<br />
These deep learning algorithms are often more perceptive to patterns<br />
than humans, allowing them to reach conclusions that might not be<br />
apparent to a doctor trying to interpret ultrasound images. “That’s<br />
where the performance of an AI algorithm may actually exceed that of<br />
a human operator,” Oikonomou said.<br />
To develop their algorithm, the researchers needed to train it to be<br />
able to recognize severe AS. To do this, they sourced a massive amount<br />
of 2D cardiac ultrasound videos from patients in the Yale New Haven<br />
Health system with no AS, non-severe AS, and severe AS. Using this<br />
dataset, the algorithm learned how to identify specific phenomena<br />
in the videos associated with each class of AS diagnosis. Once the<br />
researchers trained the algorithm to learn what to look for, they had<br />
to validate that the algorithm was truly capable of differentiating<br />
non-AS, non-severe AS, and severe AS ultrasound videos. To prove<br />
the algorithm’s success, they had it sort a new dataset from different<br />
patients in New England and California. The deep learning algorithm<br />
proved highly accurate in sorting the videos across all patient datasets.<br />
The researchers’ vision is that their algorithm can be used by any<br />
medical provider with a simple ultrasound scanner to catch AS early.<br />
This removes the existing barriers to AS diagnosis, like specialized<br />
Doppler echocardiography equipment and the training of medical<br />
providers to accurately interpret results, making AS diagnoses more<br />
accessible to patients and simpler for providers. If the algorithm<br />
is widely used, it could be a major step forward for successful AS<br />
intervention. “Hopefully, we can make this as cost-efficient as possible,”<br />
Oikonomou said. “It’s very easy to do—it takes two or three minutes,<br />
and people can probably be screened once in their lifetime.”<br />
Beyond its immediate impact in improving outcomes for AS patients,<br />
this deep learning algorithm reveals the broader potential of applying<br />
cutting-edge computer science to healthcare. “I think this could be<br />
applied to other things such as hypertrophic cardiomyopathy, which<br />
is a genetic heart condition that is very common but most people don’t<br />
ever get diagnosed,” Oikonomou said.<br />
With increasingly high patient burdens and medical staff stretched<br />
thin, it’s inevitable that some patients will slip through the cracks of<br />
the healthcare system. Machine and deep learning models could be<br />
used across a variety of applications to identify diagnoses that are<br />
sometimes missed by medical staff. The CarDS Lab’s algorithm is<br />
proof of the great positive impact that computer science and artificial<br />
intelligence stand to have on patient care and outcomes. ■<br />
8 Yale Scientific Magazine September 2023 www.yalescientific.org
Biology<br />
FOCUS<br />
CANCER: NOT<br />
JUST BAD LUCK?<br />
How Cancer May Be<br />
More Than Just<br />
Random Mutations<br />
BY SEBASTIAN REYES<br />
IMAGE COURTESY OF NIH IMAGE GALLERY<br />
It is well known that our risk for cancer increases as we age, but we still<br />
don’t understand why. How might the wrinkles marking the corners<br />
of our eyes relate to cancerous cells suddenly forming inside us?<br />
Previous research established a high correlation between cancer risk and<br />
the number of replications a cell undergoes throughout our life, leading to<br />
the hypothesis that random, unlucky mutations during cellular division<br />
are a notable driver of tumor formation. This aptly named “bad luck”<br />
hypothesis has been widely debated, with scientists questioning how the<br />
theory accounts for the impact of environmental factors. Now, researchers<br />
at Yale University are proposing an answer: an age-related chemical<br />
signature hiding in our genomes.<br />
The study, conducted by recent PhD graduate Christopher Minteer and<br />
former Yale Assistant Professor Morgan Levine explores a set of epigenetic<br />
alterations called DNA methylation—that is, chemical attachments to the<br />
genome rather than changes within the DNA sequence itself—associated<br />
with aging and risk of diseases like cancer. Through the repeated replication<br />
of astrocytes, a type of cell found in the central nervous system ideal for<br />
this type of manipulation, Minteer’s team was able to mimic the rapid,<br />
unconstrained replication of tumorous cells. Having achieved tumor-like<br />
growth, the team then designed an algorithm to quantify the epigenetic<br />
signals in the cells. They eventually identified a progressive methylation<br />
signature that they called CellDRIFT, the strength of which increased with<br />
age across multiple tissues and differentiated tumors from normal tissue.<br />
Through additional examination, Minteer’s team found that the<br />
CellDRIFT signature was elevated not only in cancerous cells, but also in<br />
healthy tissues that were predisposed to tumor formation. They examined<br />
healthy breast tissue from breast cancer patients prior to treatment and<br />
found that even the tumor-free tissues displayed an elevated CellDRIFT<br />
signature compared to non-cancerous controls, suggesting that<br />
CellDRIFT could predate the formation of tumors and serve as a warning<br />
sign. They also found that its presence was strongly correlated with poor<br />
patient survival, meaning that CellDRIFT, along with related measures,<br />
may help researchers and clinicians predict cancer aggression.<br />
“We provided further context to the ‘bad luck’ hypothesis and created<br />
a tool to better study it,” Minteer said. While the “bad luck” hypothesis<br />
links the majority of cancer risk to random, sudden mutations in the<br />
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genome, the CellDRIFT signature appears gradually. It slowly increases<br />
over time, meaning that CellDRIFT increments can vary depending on<br />
environmental factors, such as exposure to carcinogens. Thus, CellDRIFT<br />
can help provide a more thorough and unified understanding of the<br />
previously known underlying causes of tumor formation.<br />
The researchers also explored whether they could reverse or otherwise<br />
reset the CellDRIFT signature. Namely, they manipulated stem cells to<br />
“reset” through a process known as Yamanaka factor reprogramming—a<br />
process in which special genes are introduced to cells to transform them<br />
back into an unspecialized state, thus allowing them to re-develop into new<br />
types of cells. Each instance of Yamanaka factor reprogramming consists<br />
of three phases: initiation, in which the cell begins to show genetic signs<br />
of resetting, maturation, in which the bulk of the reprogramming process<br />
occurs, and stabilization, in which the cells settle into their new form.<br />
Minteer’s team observed a dramatic decrease in CellDRIFT during the<br />
maturation phase, but the signature increased again once the cells entered<br />
the stabilization phase. In other words, they found promising evidence to<br />
suggest that although CellDRIFT cannot be stopped completely, it can be<br />
impeded, thus providing a new approach to preventive cancer treatments.<br />
Minteer’s team also recognized that while CellDRIFT presence can be<br />
used to predict many aspects of cancer risk and aggression, calculating<br />
the signature is a difficult task in itself. Thus, they constructed a package<br />
to help clinicians and researchers quickly and efficiently quantify the<br />
signature, making their discovery more accessible to others unfamiliar<br />
with this field. “[The package] is uniquely suited to serve as a resource in<br />
the lab,” Minteer said. Although it still requires additional validation and<br />
experimentation, Minteer expressed excitement about the potential future<br />
uses of this package in both experimental and clinical settings.<br />
While the use of epigenetic tools in clinics is still in its infancy, the<br />
findings of Minteer’s team are promising. CellDRIFT is unique in that it<br />
considers the myriad of factors that trigger the formation of an individual’s<br />
specific tumor, rather than reducing these factors to “just bad luck.” This<br />
provision of tailored cancer diagnoses makes CellDRIFT a compelling tool<br />
for clinicians to understand the full cancer narrative, and its contribution<br />
to the debate about cancer’s origin suggests a new, encouraging role for<br />
cancer prevention. ■<br />
September 2023 Yale Scientific Magazine 9
FOCUS<br />
Computer Science<br />
REPRESENTATION<br />
IN ANIMATION<br />
Computer Science<br />
Captures The Physics<br />
of Afro-Textured Hair<br />
BY ABIGAIL JOLTEUS<br />
PHOTOGRAPH COURTESY OF FAREED SALMON<br />
In the past, in computer animation, many Black characters would<br />
have poorly animated braids, or more frequently, just have<br />
straight hair. For years, computer animations would use these<br />
inaccurate representations of tightly coiled hair, also known as afrotextured<br />
hair. Recently, as more people of color have been hired and<br />
cast for animation roles, the animation industry has moved towards<br />
becoming more diverse and inclusive than ever before.<br />
However, this increase in diversity did not translate into more<br />
accurate animation of afro-textured hair. “The way that hair<br />
has been simulated, at least since the ‘90s, has been many line<br />
segments chained together, and making them small enough gives<br />
a smooth appearance,” said Theodore Kim, an associate professor<br />
of computer science at Yale. Animating hair is achieved through<br />
various mathematical equations where the twists of each strand<br />
must be carefully simulated for accurate hair motion. “Therefore,<br />
when a character shakes their head, you can see realistic movement,”<br />
Kim said. However, this process only works for the overwhelming<br />
majority of animated characters who are white and have straight<br />
hair. “The trouble appears with the physics equations selected for<br />
simulation,” he said.<br />
A team of computer scientists at Yale have created a novel<br />
physical model that allows for more accurate animation of tightly<br />
coiled hair, more realistically capturing the way it looks and moves.<br />
“We were concerned with three different types of elastic energy<br />
for hair: stretching, bending, and twisting energies,” said Haomiao<br />
Wu, one of the lead researchers on the project. “These energies<br />
constrain how the strands behave in an elastic way. We proposed<br />
a different set of those three energies for a model so that it is more<br />
stable.” In other words, they wanted to capture the true essence of<br />
afro-textured hair using sophisticated mathematical modeling.<br />
Their isotropic, hyperelastic model was specifically designed for<br />
better simulation of tightly coiled hair. “Isotropic means that no<br />
matter the direction, the restorative force is the same,” said Alvin<br />
Shi, another one of the lead researchers on the study. Restorative<br />
force is the force needed for an object to return to its initial size<br />
and shape. In this case, it enables a hair strand to return to its initial<br />
coiled state, which better captures afro-textured hair. This model is<br />
also faster, simpler, and more robust than previous models.<br />
The researchers devised this model by discarding the previous<br />
assumption for mathematical equations to simulate the curling<br />
pattern of each strand and instead consider large bends and<br />
torsions, as well as assuming, to a certain extent, that the hair is<br />
non-straight. While this model was designed for kinky, curly, or<br />
coily hair, the researchers discovered that it is also effective for<br />
straight hair.<br />
As with all simulations, there are flaws. Some of these limitations<br />
include the scaling behavior of tight, coily hair and lack of variation<br />
in how the hair can look. Currently, the model can account for only<br />
two different appearances of afro-textured hair: a clumped look,<br />
well-defined curls, and a more picked-out look, or fluffed-out<br />
afro-textured hair. By decreasing the radius of a wisp—a clump of<br />
hair strands common in afro-textured hair—but keeping the same<br />
total number of hair strands, a more picked-out look is obtained.<br />
However, these looks are not incredibly realistic compared to reallife<br />
individuals with the same hair type. “We are looking to improve<br />
on the realistic aspect of our model,” Shi said.<br />
For the next steps, the researchers plan to conduct further<br />
experiments with the realism of the simulated hair and possibly test<br />
an anisotropic model, meaning the pattern is different in various<br />
directions, which could lead to better animations of different<br />
hairstyles with afro-textured hair.<br />
While no animated content or games are perfect, it is important<br />
that Black individuals see themselves adequately represented in<br />
the media that they consume. As the creators of one of the first<br />
models specifically for tight, coily hair, the team also hopes that<br />
other researchers will be inspired to conduct similar research. “We<br />
are looking forward to seeing more and more research in this field,<br />
not just from us but other researchers as well,” Wu said. Ultimately,<br />
they want their model to lead to greater and better racial and ethnic<br />
representation in animated games and movies. “It might take<br />
longer than we wish for these techniques to be implemented, but<br />
we are hoping as soon as possible,” Wu said. ■<br />
10 Yale Scientific Magazine September 2023 www.yalescientific.org
Molecular Biology<br />
FOCUS<br />
SUPER-SIZING<br />
LIFE’S SMALLEST<br />
SECRETS<br />
Pushing The Boundaries<br />
of Microscopy<br />
BY KARA TAO<br />
PHOTOGRAPHY COURTESY OF EMILY POAG<br />
Let’s turn the clock way back to when you consisted of only a<br />
small clump of cells. How does this tiny clump of cells know to<br />
transform into various cell types throughout your body, from hair<br />
and eyes to lips and legs? It turns out that these instructions are encoded<br />
in our genome. However, our genome is initially “silent.” It needs to be<br />
activated and reprogrammed through a process called zygotic genome<br />
activation so that our cells can properly differentiate into specific cell<br />
types in our body.<br />
The Giraldez lab at Yale specifically investigates the cellular<br />
mechanisms of this process, which involve a variety of interactions<br />
between protein ‘factors’ and DNA that work together to transform<br />
the “silent” state of the genome into the activated state. “It’s kind of like<br />
erasing the blackboard and writing new instructions,” said Antonio<br />
Giraldez, the Fergus F. Wallace Professor of Genetics. “We’re trying<br />
to understand the factors that erase the previous instructions and the<br />
factors that instruct the genome to employ the first cascade of events<br />
that will lead to development.”<br />
Traditionally, researchers have relied on indirect biochemical methods<br />
to unravel the intricacies of this process, as the existing visualization<br />
techniques have presented considerable limitations. “We wondered if<br />
we could actually come up with a new way to visualize what happens<br />
inside of these clusters,” said Mark Pownall, a member of the Giraldez<br />
lab who first looked into this research direction. In collaboration with<br />
the Bewersdorf lab at Yale, Pownall adapted their already-established<br />
technique of pan-expansion microscopy (pan-ExM), incorporating<br />
labeling of protein, RNA, and DNA to create Chromatin Expansion<br />
Microscopy (ChromExM). Pan-expansion microscopy involves fixing<br />
cells to an expandable gel called a hydrogel that swells via addition<br />
of certain functional groups. By layering multiple hydrogels on top of<br />
each other, the cells take on a larger size that can be better resolved<br />
under a microscope.<br />
The cell, and specifically the chromatin that makes up our<br />
chromosomes, expands to become four thousand times larger, allowing<br />
for a never-before-seen look into the small-scale interactions that<br />
thus far, researchers have only been able to theorize about. “This has<br />
allowed us to start measuring distances that are ten times higher in<br />
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resolution than what we have ever captured before,” Giraldez said. “This<br />
has revealed how the models and the cartoons we are drawing from<br />
biochemical experiments can be visualized for the first time.”<br />
One of the main concerns of expansion microscopy was whether the<br />
cell’s proportions could be maintained during the expansion process. To<br />
ensure that the cell expanded proportionally, the Giraldez lab developed<br />
a technique where the initial cell was marked with parallel stripes, and<br />
if the stripes remained parallel after expansion, it would have exhibited<br />
proportional growth. “This showed us that we preserved these stripes<br />
really well after they were cleaved, which was one hint that we actually<br />
preserved chromatin structure,” Pownall said.<br />
With this novel technique in hand, the Giraldez lab could finally<br />
visualize the specific factors involved in activating the genome. Using<br />
ChromExM, they were able to study the function of Nanog, a protein<br />
that binds to a “gene enhancer” region of DNA that stimulates the<br />
activation of genes involved in development. Although Nanog had<br />
been shown to interact with RNA polymerase, located at the promoter<br />
region of the gene where the polymerase would initially bind to initiate<br />
transcription of DNA to mRNA, it was unclear whether these structures<br />
actually required transcription to form. By using ChromExM, they<br />
found that the Nanog protein was initially in close contact with RNA<br />
polymerase, but once transcription was initiated, the protein separated<br />
itself from the growing strand of mRNA. The Giraldez lab termed this<br />
interaction the “kiss-and-kick model,” where transcription acts as the<br />
“kick” to separate the enhancer and promoter regions.<br />
The development of the human body is an incredibly complex<br />
process directed by genetic codes regulated by countless factors that<br />
interact with chromatin and different organelles in our cells. The novel<br />
technique of ChromExM not only allows us to visualize these processes,<br />
but is also accessible and applicable to other fields of study, as it only<br />
requires a confocal microscope that can be found in biological research<br />
labs. “I think that this could add a fundamental tool to the global toolbox<br />
to really understand how different molecules interact in the nucleus by<br />
visualizing these fundamental processes of life,” Giraldez said. “The<br />
accessibility is great, and the possibilities to apply ChromExM to other<br />
approaches is very large.” ■<br />
September 2023 Yale Scientific Magazine 11
FOCUS<br />
Electrical Engineering<br />
WHY TINY PATTERNS MEAN BIG THINGS<br />
FOR THE FUTURE OF SEMICONDUCTORS<br />
BY WILLIAM ARCHACKI<br />
The moiré effect is a phenomenon<br />
you can witness with just a marker<br />
and paper. First, take your marker<br />
and draw a honeycomb pattern of<br />
hexagons on two sheets of paper. Now lay<br />
them atop one another askew, rotating the<br />
top sheet slightly. By combining these two<br />
lattices, you should see regular, repeating<br />
patterns much larger than any individual<br />
hexagon. This is the moiré effect in action:<br />
from a distance, the overlapping hexagons<br />
make a larger tessellation that seems to<br />
alternate between light and dark regions.<br />
Now imagine if atoms stood at the<br />
vertices of every hexagon on the paper,<br />
connected to their neighbors by chemical<br />
bonds. That’s the structure of a moiré<br />
material. At an atomic scale, the repeated<br />
patterns of the moiré effect change how<br />
light interacts with a material and, in<br />
turn, how the material transmits electrical<br />
signals resulting from light.<br />
In a recent Nature Materials publication<br />
led by Fengnian Xia, professor of electrical<br />
engineering at Yale, the team innovated<br />
upon moiré materials. By finding a<br />
more controllable way to produce the<br />
moiré effect at an atomic scale, they have<br />
made a material that has a wide range<br />
of useful physical properties that may<br />
pave the way for a new generation of<br />
optical sensors.<br />
Scientists vs. Thermodynamics<br />
The new moiré material recipe by Xia<br />
and his colleagues starts with three simple<br />
ingredients: tungsten, sulfur, and selenium.<br />
When heated in a furnace through a<br />
process referred to as chemical vapor<br />
deposition, these three elements combine<br />
into flat, hexagonal lattices. The vertices<br />
are occupied by atoms of tungsten, sulfur,<br />
and selenium. After heating for a second<br />
time with a supply of the same elements in<br />
different ratios, an additional layer forms<br />
on top of the existing hexagonal lattice,<br />
this time with a slightly different spacing<br />
between its atoms—a different lattice<br />
constant. The alignment of differentlyspaced<br />
layers signals success: the moiré<br />
effect is present. Now, it’s a matter of lattice<br />
size rather than rotation.<br />
It has historically been a challenge for<br />
researchers to fabricate moiré materials<br />
because of the natural way that layers<br />
form. The most stable way for two<br />
identical layers to stack results in a<br />
perfect alignment that never produces<br />
the moiré effect. So, rather than using<br />
the conventional ‘twistronics’ approach<br />
to moiré material fabrication, which<br />
fights against thermodynamics to force<br />
the layers to rotate, this new approach<br />
from Xia’s group relies on variations in<br />
the spacing of atoms. In their recipe,<br />
the moiré effect is created by stacking<br />
hexagons of different sizes, rather than<br />
different orientations.<br />
“Twisting two layers at a specific twist<br />
angle is not the most stable form of<br />
matter,” said Matthieu Fortin-Deschênes, a<br />
postdoctoral fellow in Xia’s research group<br />
and first author on the paper. “Basically,<br />
we came up with an approach to directly<br />
grow these moiré patterns with tunable<br />
spacing. Instead of twisting, we grow them<br />
with different lattice parameters to tune<br />
the moiré periodicity.”<br />
By precisely varying the concentrations<br />
of sulfur and selenium relative to tungsten,<br />
the researchers saw that the pattern they<br />
form has a “tunable period”. In other words,<br />
they can control how large the patterns<br />
appear. With a tunable period, there is a<br />
new world of possibilities. “If you’re able<br />
to tune the periodicity, you’re able to tune<br />
the properties of the material,” Fortin-<br />
Deschênes said. Tuning properties is a big<br />
deal for electrical engineers. The next step<br />
is figuring out how to leverage these tunable<br />
properties for use in real technologies.<br />
Tiny Materials, Big Implications<br />
Working on these materials has gotten<br />
Xia and his colleagues thinking a lot<br />
about light. What kind of information<br />
can we glean from light? For one answer,<br />
look to the astronomers. When studying<br />
exoplanets, they often examine the spectra<br />
of light that passes through the planets’<br />
atmospheres. By using spectroscopy, a<br />
crucial analytical technique that works<br />
like forensics for light, they deduce which<br />
gases are floating around in a breath’s<br />
worth of air many millions of miles away.<br />
And waves of light have more parameters<br />
than just their spectra. Measuring light’s<br />
polarization can give insights into what<br />
substances the light has interacted with.<br />
For example, light that reflects off water is<br />
12 Yale Scientific Magazine September 2023 www.yalescientific.org
Electrical Engineering<br />
FOCUS<br />
Matthieu Fortin-Deschênes operating machinery in the lab.<br />
polarized because the process of reflection<br />
forces all the light waves to oscillate<br />
within the same plane. Other parameters<br />
of interest like intensity or coherence can<br />
each be measured with dedicated pieces of<br />
lab equipment. For Xia, these parameters<br />
of light pose an exciting question: What if<br />
it were possible to pick up on the wealth of<br />
information provided by light using just a<br />
single sensor?<br />
The new moiré material has a special way<br />
of interacting with light and transmitting<br />
electric current. Just as bumps on a hill<br />
change the way water flows, moiré-induced<br />
variations in the invisible landscape of the<br />
material’s electric potential change how<br />
electrons move from one point to another.<br />
Incoming light gets absorbed by the<br />
material and starts a flow of electrons, and<br />
when that flow of electrons is recorded<br />
as a current or its corresponding voltage<br />
drop, information about the light’s source<br />
is conveyed somewhere within the data.<br />
The challenge, then, is to decode the data<br />
and reveal the secrets hidden within the<br />
material’s electric signals.<br />
“This material is highly tunable, and<br />
it interacts with light very strongly.<br />
That would allow us to combine this<br />
reconfigurable material with the latest<br />
deep learning algorithms,” Xia said. “In<br />
another 2022 paper, we used deep learning<br />
to realize the detection of many parameters<br />
of light simultaneously.” Their approach—<br />
referred to as deep sensing—could change<br />
how scientists use light. Rather than just<br />
spectroscopy, scientists could tap into new<br />
www.yalescientific.org<br />
Photography by Paul-Alexander Lejas<br />
information carried by light if they watch<br />
how all the parameters change together.<br />
“We can relate this to image recognition,”<br />
Xia said. “This high-dimensional<br />
photoresponse contains all the information<br />
we want to know, but we don't know how to<br />
extract this information.” In the same way<br />
that a deep learning algorithm figures out<br />
to differentiate images of cats from images<br />
of dogs, an algorithm might learn to<br />
correlate the complex electric signals from<br />
the sensor to any kind of data a scientist<br />
might be examining. “Let’s assume you<br />
want to know the concentration of a certain<br />
gas. You can do that by measuring the<br />
ABOUT THE AUTHOR<br />
absorption spectrum. But you don't have<br />
to do that. You can skip that process. You<br />
can go directly from the photoresponse<br />
to the concentration of the gas if you do<br />
enough training correctly,” Xia said.<br />
Not Just Tungsten<br />
Although the recent paper only covers<br />
one moiré material, the researchers<br />
behind it are hopeful that the fabrication<br />
process can be applied in other ways.<br />
“The intention of studying the growth<br />
mechanisms is to understand the<br />
fundamentals of the growth processes and<br />
then try to extrapolate to other systems,”<br />
Fortin-Deschênes said. Of special interest<br />
is graphene, a substance made of twodimensional<br />
sheets of carbon atoms, which<br />
could be mixed with silicon in the same<br />
way that sulfur was mixed with selenium.<br />
The hope is that each new system may<br />
have its own set of unique properties that<br />
can be applied to electrical engineering<br />
challenges of the future.<br />
“Since we have so many properties that<br />
emerge and that can be easily tuned, we<br />
can expect that we will find something that<br />
is very useful using these moiré materials,”<br />
Fortin-Deschênes said. Novel fabrication<br />
methods, such as this one, are creating<br />
possibilities for new atomic arrangements<br />
of materials. By changing the way energy<br />
and electrons dance at the quantum scale,<br />
researchers may reshape the future of<br />
semiconductor devices. ■<br />
A R T B Y S T E V E B L A N C O<br />
WILLIAM ARCHACKI<br />
WILLIAM ARCHACKI is a sophomore Chemistry major in Pierson College. Aside from <strong>YSM</strong>, Will writes<br />
and edits for Cortex Magazine. He conducts research on superconductivity in the Pfefferle lab group and<br />
goes on ecological adventures with the Yale Birding Club.<br />
THE AUTHOR WOULD LIKE TO THANK Fengnian Xia and Matthieu Fortin-Deschênes for sharing their<br />
expertise and enthusiasm in their field.<br />
REFERENCES:<br />
Brennan, P. “Hubble Probes Atmospheres of Exoplanets in TRAPPIST-1 Habitable Zone.” Exoplanet<br />
Exploration: Planets Beyond Our Solar System, 24 Sept. 2020, NASA Space Telescope Institute. https://<br />
exoplanets.nasa.gov/news/1483/hubble-probes-atmospheres-of-exoplanets-in-trappist-1-habitablezone.<br />
Cronin, T. W., & Marshall, J. (2011). Patterns and properties of polarized light in air and water. Philosophical<br />
transactions of the Royal Society of London. Series B, Biological sciences, 366(1565), 619–626. https://doi.<br />
org/10.1098/rstb.2010.0201<br />
Fortin-Deschênes, Matthieu, et al. “Van Der Waals Epitaxy of Tunable Moirés Enabled by<br />
Alloying.” Nature Materials, Nature Portfolio, Aug. 2023. https://10.1038/s41563-023-01596-z. doi.<br />
org/10.1111/j.1475-2743.2002.tb00266.x<br />
September 2023 Yale Scientific Magazine 13
FOCUS<br />
Planetary Sciences<br />
THAT MAGNETIC TOUCH<br />
ASTEROIDS HITTING ASTEROIDS<br />
SOLVING THE MYSTERY OF ASTEROIDS’ MAGNETIC FIELDS<br />
BY ELIZABETH WATSON | ART BY ANNLI ZHU<br />
In 2017, scientists unearthed a magnetic<br />
puzzle in our own solar neighborhood,<br />
beginning with samples taken from a<br />
series of iron-rich meteorites that had fallen<br />
to Earth. Upon analyzing the samples, the<br />
team detected evidence of magnetism. This<br />
discovery was important because it meant<br />
that the parent asteroid of these meteorites<br />
was somehow capable of internally generating<br />
its own magnetic field—a phenomenon that<br />
was difficult to explain.<br />
The same year this discovery was made,<br />
planetary scientist Zhongtian Zhang, now at<br />
the Carnegie Institution for Science’s Earth<br />
and Planets Laboratory, began his graduate<br />
studies at Yale. Zhang was intrigued by the<br />
results of the meteorite analysis, but like<br />
the rest of the scientific community, he was<br />
confused as to how an asteroid like this one<br />
could feasibly generate a magnetic field. “The<br />
community had been puzzled with this as<br />
well, and I hadn’t been able to come up with a<br />
solution for a long time,” Zhang said.<br />
Six years later, in a paper published in<br />
the Proceedings of the National Academy of<br />
Sciences this July, Zhang and David Bercovici,<br />
Frederick William Beinecke Professor of Earth<br />
and Planetary Sciences, may have figured out<br />
the origin of these magnetic meteorites. The<br />
secret may lie in asteroids, and what happens<br />
when they collide with one another.<br />
The Paradox of Magnetism<br />
Planetary bodies generate magnetic fields<br />
through mechanisms known as ‘dynamos.’ In<br />
general, dynamos rely on convective motion,<br />
in which less dense material rises up as more<br />
dense material sinks down. Take Earth, for<br />
example: the iron-nickel core at the heart of<br />
our planet solidifies from the inside out in a<br />
process called outward solidification, causing<br />
the convective motion necessary to generate<br />
a magnetic field. Understanding dynamos<br />
can provide insights into a planetary body’s<br />
internal structures and evolutionary histories.<br />
The cores of asteroids, however, are a different<br />
matter altogether. Meteorites originate from<br />
asteroids, which are fragments of rocks in<br />
space that date back nearly 4.5 billion years.<br />
Meteorites that are rich in iron, specifically,<br />
come from the cores of asteroids. There are<br />
approximately 1.3 million asteroids in our<br />
solar system, most of which reside in the<br />
Asteroid Belt between Jupiter and Mars. Of<br />
these, only eight percent are made of metal.<br />
The liquid cores of these metal asteroids are<br />
known to cool from the outside in through<br />
a process called inward solidification. This is<br />
why these metal asteroids were not thought to<br />
14 Yale Scientific Magazine September 2023 www.yalescientific.org
Planetary Sciences<br />
FOCUS<br />
be capable of generating their own magnetic<br />
fields—inward solidification directly inhibits<br />
convection and suppresses the traditional<br />
magnetic field dynamo.<br />
When Asteroids Collide<br />
When thinking about this paradox, Zhang<br />
turned to a previous project of his on rubblepile<br />
asteroids, which are formed when asteroid<br />
fragments coalesce into new objects due to<br />
gravitational forces. “I started to think of<br />
things in terms of collisions and formation of<br />
rubble piles,” Zhang said. “I was thinking that<br />
this may be the solution to the problem that’s<br />
been on my mind for quite a while.”<br />
Zhang deduced that in order for the<br />
metallic core of an asteroid to become<br />
exposed in the first place, a collision must<br />
have taken place in a process termed ‘mantle<br />
unstripping’ by means of another asteroid.<br />
The force of an asteroid hitting another<br />
asteroid would cause the mantle of the<br />
original asteroid to be broken down, exposing<br />
the resulting asteroid fragments, alongside<br />
the core, directly to the environment of space.<br />
In the aftermath of a collision, an asteroid’s<br />
molten core would have broken apart and<br />
reformed, and if a small portion of metal<br />
fragments were able to cool down sufficiently<br />
before falling back into the molten core, they<br />
would sink downwards. Bercovici compared<br />
the process to dropping ice cubes in hot tea,<br />
except the ice cubes sink. These cold fragments<br />
that sink to the center would then extract<br />
heat from the overlying liquid and cause the<br />
outward solidification capable of driving<br />
a magnetic field. Meanwhile, the inward<br />
solidification that occurred from the surface<br />
would produce cold material to preserve this<br />
field. “It provides an implication about how<br />
asteroids work, [how they were] formed and<br />
disrupted,” Zhang said. “It provides a new<br />
scenario for people studying magnetic fields.”<br />
Initially, Zhang set out to determine the size<br />
of the asteroid fragments necessary to power<br />
a dynamo in this fashion. The ideal fragment<br />
would be small enough to cool efficiently in<br />
the vacuum of space, but also large enough to<br />
remain sufficiently cold after sinking through<br />
the hot liquid region of the core, according<br />
to the two researchers. Zhang modeled the<br />
thermal regulation of the fragments and<br />
determined that the ideal fragment size is<br />
approximately ten meters, which coincided<br />
with his calculations for the average fragment<br />
size created by these collisions. “It turns<br />
out that fragmentation size is right in the<br />
www.yalescientific.org<br />
Goldilocks regime for having the "right" ice<br />
cubes,” Bercovici said. “Bottom line—that was<br />
cool, pun not really intended.”<br />
To Psyche And Beyond<br />
Zhang performed additional modeling and<br />
determined that the convection generated<br />
from this theory would be adequate to power a<br />
magnetic field for at least one million years. This<br />
research could have important implications for<br />
what we understand about asteroids, including<br />
NASA’s future Psyche Mission.<br />
Psyche is an asteroid that has long been a<br />
subject of fascination for some members of<br />
the scientific community, as it may be the ironnickel<br />
core of a planet that formed billions of<br />
years ago. The mission recently launched on<br />
October 13, 2023, and is anticipated to reach<br />
Psyche in 2029. Once in orbit, the hope is that<br />
the mission will allow scientists to develop a<br />
deeper understanding of our solar system’s<br />
history, as well as that of our own planet,<br />
through the information collected from<br />
Psyche. Zhang and Bercovici’s research could<br />
be crucial to understanding Psyche’s origin,<br />
as well as planetary evolution as a whole.<br />
Bercovici is also a principal investigator on<br />
the Psyche Mission, which was the source of<br />
funding for this project.<br />
“I decided to be part of the mission because<br />
of my interest in planetary sciences in the first<br />
place,” Zhang said. “It was also a personal<br />
interest in these kinds of things and being<br />
part of the Psyche mission bolstered me to<br />
look at this as a problem of magnetic fields<br />
and meteorite observations.” Zhang hopes<br />
ABOUT THE AUTHOR<br />
IMAGE COURTESY OF NASA<br />
An illustration of the Psyche Spacecraft.<br />
to expand this work in new directions in the<br />
future, hopefully involving information about<br />
metal asteroids obtained from the Psyche<br />
Mission to understand the asteroid’s history.<br />
Bercovici enjoyed working with Zhang<br />
over the course of the project, citing Zhang’s<br />
tenacity after having published several ‘hardwon’<br />
papers. “Zhongtian is one of the most<br />
creative, deep-thinking, and versatile students<br />
or colleagues I’ve had the pleasure of working<br />
for,” Bercovici said. “Sometimes he was like a<br />
mustang bolting into the hills with new ideas,<br />
and my job was to help him close the loop and<br />
explain his ideas clearly. Having students and<br />
postdocs much smarter than me is always fun,<br />
and my job is to make sure they communicate<br />
well with mere mortals, like myself.”<br />
To understand the universe, one must<br />
acknowledge its mysteries—including the<br />
ones that exist in our own solar neighborhood.<br />
After six years of mystery, this magnetic<br />
meteorite puzzle may finally have been solved,<br />
and its lessons applied forward, thanks to the<br />
work of these two Yale researchers. ■<br />
ELIZABETH WATSON<br />
ELIZABETH WATSON is a junior in Pauli Murray College double majoring in Ecology and Evolutionary<br />
Biology and the Humanities. In addition to writing for <strong>YSM</strong>, she is the head of the magazine’s social<br />
media team. Outside of <strong>YSM</strong>, she conducts neuroscience research at the Yale School of Medicine, serves<br />
the editor-in-chief of Hippo Literary and Arts Magazine, and enjoys playing Dungeons and Dragons.<br />
THE AUTHORS WOULD LIKE TO THANK Zhongtian Zhang and David Bercovici for their time and<br />
enthusiasm in sharing their research.<br />
REFERENCES:<br />
Zhang, Z., & Bercovici, D. (2023). Generation of a measurable magnetic field in a metal asteroid with a<br />
rubble-pile core. Proceedings of the National Academy of Sciences of the United States of America, 120(32).<br />
https://doi.org/10.1073/pnas.2221696120.<br />
Psyche. NASA Jet Propulsion Laboratory: California Institute of Technology. https://www.jpl.nasa.gov/<br />
missions/psyche.<br />
Missions: Psyche. NASA Solar System Exploration. https://solarsystem.nasa.gov/missions/psyche/<br />
overview/.<br />
Bryson, J.F., Weiss, B.P., Harrison, R.J., Herrero-Albillos, J., & Kronast, F. (2017). Paleomagnetic evidence<br />
for dynamo activity driven by inward crystallisation of a metallic asteroid. Earth and Planetary Science<br />
Letters, 472, 152-163. https://doi.org/10.1016/j.epsl.2017.05.026.<br />
September 2023 Yale Scientific Magazine 15
FOCUS<br />
Ophthalmology<br />
KEEP AN EYE ON IT<br />
BREAKTHROUGHS IN THE RETINA<br />
BY RISHA CHAKRABORTY AND JOHNNY YUE<br />
16 Yale Scientific Magazine September 2023 www.yalescientific.org
Ophthalmology<br />
FOCUS<br />
What if you suddenly had blurry<br />
vision, couldn't recognize familiar<br />
faces, or had difficulty adapting<br />
to dimly lit places? This is the reality<br />
for people with age-related macular<br />
degeneration, also known as AMD, one<br />
of the most prevalent causes of vision loss<br />
that affects around 200 million people in<br />
the world.<br />
In AMD, damage occurs in the macula, an<br />
oval-shaped area at the center of the retina.<br />
The retina consists of a layer of cells known<br />
as photoreceptors, which are crucial for<br />
converting light entering the eye into signals<br />
sent to the brain. The macula is specifically<br />
responsible for sharp and central vision.<br />
Thus, someone with AMD usually has<br />
difficulty deciphering fine details. There are<br />
limited effective therapies for the disease—<br />
current treatments such as vitamins and<br />
minerals only slow disease progression, but<br />
do not stop or reverse it.<br />
Yale scientists are among those who have<br />
joined the cause to find out more about AMD<br />
disease pathology. From discovering possible<br />
therapeutic targets for AMD and other<br />
neurodegenerative diseases to uncovering<br />
a quantum chemistry reaction in the retina,<br />
their findings could not only inform potential<br />
AMD treatments, but also offer applications<br />
far beyond the eye.<br />
A Window Into Neurodegeneration<br />
In a recent study published in Nature<br />
Communications, Yale Assistant Professor<br />
Brian Hafler and a team of Yale researchers<br />
found that AMD, which is itself a<br />
neurodegenerative disease of the retina,<br />
could serve as a system for understanding<br />
other neurodegenerative diseases such as<br />
Alzheimer’s disease and multiple sclerosis.<br />
To arrive at this finding, they developed a<br />
novel approach to understanding AMD<br />
and its cellular pathology.<br />
Hafler and his team utilized single-cell<br />
data and machine learning techniques to<br />
pinpoint the populations of cells in the<br />
retina that play a prominent role in the<br />
disease progression of AMD. This study built<br />
upon previous research in the retina which<br />
highlighted the overall role of inflammation<br />
in the pathology of macular degeneration.<br />
The team isolated 70,973 individual retinal<br />
cells from seventeen different human retinas<br />
with different stages of disease and healthy<br />
controls. “This allowed us to build a unique<br />
When medical research is applied to patient<br />
care, we can uniquely translate novel<br />
therapeutic approaches for diseases like AMD.<br />
road map into the genetic networks driving<br />
inflammation in macular degeneration<br />
and hopefully to develop new therapeutic<br />
targets,” Hafler said.<br />
To analyze these cells, the team designed<br />
a novel collection of machine learning tools<br />
which they termed “Cellular Analysis with<br />
Topology and Condensation Homology,” or<br />
CATCH. At the core of CATCH is a method<br />
known as diffusion condensation, which<br />
identifies similar groups of cells based on<br />
how they are pulled toward the weighted<br />
average of neighboring cells in space. This<br />
method enabled the team to pinpoint two<br />
populations of activated glial cells (cells<br />
whose primary role is to support neurons):<br />
astrocytes and microglia. Astrocytes provide<br />
neuroprotective, structural, and metabolic<br />
nourishment to nerve cells, while microglia<br />
are the immune cells of the brain and mount<br />
responses to pathogens. Both were found to<br />
be activated in the early phase of AMD.<br />
Surprisingly, similar activation profiles<br />
were found to dominate the early phases of<br />
other neurodegenerative diseases, such as<br />
Alzheimer’s disease and multiple sclerosis.<br />
This association led the researchers to believe<br />
that early stages of neurodegenerative disease<br />
progression generally utilize a common<br />
mechanism involving the activation of<br />
glial cells. It also suggests that the retina<br />
can potentially be a unique system for<br />
developing new therapeutic strategies to treat<br />
neurodegenerative diseases.<br />
Then, using single-cell data from Alzheimer’s<br />
and multiple sclerosis studies, Hafler<br />
and his team were able to characterize<br />
specific cellular interactions that induce<br />
inflammation, which may be a common<br />
characteristic of neurodegenerative disease<br />
progression. They first identified interleukin-<br />
1β, a protein that signals immune cells to<br />
mount and induce a response, that was<br />
derived from the microglial cells activated<br />
in AMD. Using a computational technique,<br />
they found that interleukin-1β signals for<br />
astrocyte activation are pro-angiogenic,<br />
meaning that they enhance blood vessel<br />
formation. This observation lined up with<br />
the typical symptoms observed in wet<br />
AMD, an advanced stage<br />
of AMD. In late stages of<br />
AMD, blood vessels can<br />
abnormally form, grow, and leak beneath the<br />
macula. This bleeding can distort the retina<br />
and impair one’s central vision.<br />
Hafler’s study suggests that targeting<br />
astrocytes and microglia should be further<br />
considered when attempting to treat<br />
neurodegenerative diseases. Anti-angiogenic<br />
medications are currently the primary<br />
treatment, but they are only effective in<br />
advanced stages of the disease. To fill in<br />
the gap, interleukin-1β may be an effective<br />
target. With Hafler’s deep understanding of<br />
AMD both in a clinical and research setting,<br />
his results show promise towards moving<br />
forward in the fight against AMD. “My clinical<br />
practice is what drives my benchwork in the<br />
lab,” Hafler said. “When medical research<br />
is applied to patient care, we can uniquely<br />
translate novel therapeutic approaches for<br />
diseases like AMD.”<br />
How Does Melanin Protect The Retina?<br />
A second study, published in PNAS, found<br />
a quantum chemistry reaction that could<br />
explain how melanin protects the retina<br />
from age-related macular degeneration.<br />
Yale scientist Douglas Brash, a physicist by<br />
training and co-author of the study, did not<br />
expect to investigate AMD. But one day, he<br />
performed an experiment on melanocytes,<br />
which are special melanin-producing cells.<br />
Melanin is a natural pigment that shows up<br />
across the body, from the eyes to the skin.<br />
In the skin, melanin accumulates with UVlight<br />
exposure. In the retina, melanin exists<br />
in tiny granules at the photoreceptor layer;<br />
however, its function is almost completely<br />
unknown. Brash wanted to see what would<br />
www.yalescientific.org<br />
September 2023 Yale Scientific Magazine 17
FOCUS<br />
Ophthalmology<br />
happen when melanocytes were UVirradiated.<br />
Cells that are UV-irradiated<br />
develop a specific type of DNA damage<br />
called cyclobutane dimers.<br />
Brash eventually showed that, when<br />
exposed to UV radiation, melanin was<br />
oxidized by free radicals—meaning that<br />
its chemical structure lost electrons—to<br />
produce dioxetane, a chemical compound<br />
on melanin that then splits to give a<br />
molecule with a similar high-energy state<br />
to ultraviolet light in sunlight. The radicals<br />
and dioxetanes continued long after the UV<br />
light was turned off. Dioxetane’s high-energy<br />
state was a specific kind called a triplet state,<br />
which is capable of initiating reactions that<br />
ordinary chemistry cannot. He also knew<br />
that melanin was found in many places<br />
in the body, such as the eye and the ear,<br />
and the two radicals behind its oxidation,<br />
superoxide and nitric oxide, were found in<br />
many conditions such as inflammation.<br />
“These [are] events that can’t not happen.<br />
Why aren’t we dead?” Brash recalled thinking.<br />
Could the high-energy reaction cause<br />
deafness and blindness? A surprising clue<br />
to the exact opposite conclusion came from<br />
Ulrich Schraermeyer, an ophthalmologist at<br />
the University of Tubingen in Germany, who<br />
had heard about Brash’s work with melanin<br />
chemistry. Schraermeyer had an idea that<br />
completely opposed the norm<br />
ten years ago. He suggested that<br />
perhaps melanin actually had a<br />
protective role in the retina.<br />
For years, he had been<br />
working on studies to show<br />
that when melanin was<br />
associated with another<br />
molecule called<br />
lipofuscin, the retina<br />
was less susceptible<br />
to macular<br />
degeneration.<br />
Lipofuscin, a<br />
pigment that<br />
accumulates in the<br />
retina with age, is associated<br />
with neurodegeneration in AMD,<br />
but its exact composition is unclear.<br />
While Schraermeyer was convinced of the<br />
critical involvement of melanin in AMD<br />
prevention, he could not figure out the<br />
chemistry. And while Brash was intrigued<br />
by melanin having a protective role, the<br />
mechanism would need to be proven.<br />
In Schraermeyer’s initial experiments, he<br />
proved many drugs could actually slow or<br />
prevent macular degeneration in mice and<br />
monkeys. Brash noticed that these drugs were<br />
all chemicals that could create triplet states,<br />
the unique high-energy chemical state that<br />
Brash had previously created in melanin after<br />
it was treated with radicals. This led to their<br />
theory that the dioxetane in melanin that led<br />
to the triplet state was the step responsible for<br />
melanin’s protective role in the retina.<br />
In his initial experiments, Schraermeyer<br />
showed that under electron microscopy, a<br />
type of imaging technique used to visualize<br />
subcellular structures, melanin was often<br />
seen together with lipofuscin in the retina<br />
in what is called melanin-lipofuscin (MLF)<br />
granules. He observed that MLF granules<br />
accumulated in the eyes of humans above<br />
the age of sixty. Building on this observation,<br />
the group showed that the toxic lipofuscin<br />
component of MLF granules could be<br />
degraded by treating mice with a nonmelanin<br />
molecule that was in a triplet state.<br />
The degradation was blocked if mice also<br />
received a molecule that siphons the triplet<br />
energy away. Thus, it seemed like melanin<br />
chemiexcitation, using chemicals to create<br />
a high-energy state, and melanin-lipofuscin<br />
association could be studied as a pathway for<br />
lipofuscin degradation.<br />
Schraermeyer believes that upregulating<br />
melanin in the retina could be a therapeutic<br />
target. Having already shown that people<br />
lose melanin in the retina with age, he<br />
theorizes that the melanin is being<br />
used up in its protective<br />
role throughout one’s<br />
life. Brash, on the other<br />
hand, is convinced about<br />
the importance of dioxetane<br />
chemistry, but not so much<br />
about melanin itself. “I’m willing<br />
ABOUT THE<br />
AUTHORS<br />
to bet<br />
that as you<br />
get older, the<br />
melanin may well<br />
contribute to AMD,<br />
so it’s like a double-edged<br />
sword,” Brash said. Brash’s<br />
therapeutic goal is to get tripletstate<br />
precursors into the eye so that<br />
dioxetane chemistry can be harnessed<br />
for AMD prevention.<br />
Seeing Eye-to-Eye<br />
While Hafler and Brash took two very<br />
different approaches to characterizing<br />
some of the underlying mechanisms of<br />
AMD, their findings both pave a new<br />
way forward for the development of<br />
potential treatments. With scores of<br />
scientists studying AMD from various<br />
specialties and backgrounds, the pursuit<br />
of an effective treatment that accounts for<br />
multiple mechanisms grows increasingly<br />
hopeful—while potentially also addressing<br />
diseases beyond the retina as well. ■<br />
RISHA CHAKRABORTY<br />
JOHNNY YUE<br />
RISHA CHAKRABORTY is a third-year Neuroscience and Chemistry major in Saybrook<br />
College. In addition to writing for <strong>YSM</strong>, Risha plays trumpet for the Yale Precision Marching<br />
Band and La Orquesta Tertulia, volunteers at YNHH, and researches Parkinson’s Disease at<br />
the Chandra Lab.<br />
JOHNNY YUE is a second-year student majoring in Molecular, Cellular, and Developmental<br />
Biology in Trumbull College. Outside of <strong>YSM</strong>, Johnny volunteers at HAVEN Free Clinic and<br />
researches alcohol use disorder in the Cosgrove Lab at the Yale School of Medicine.<br />
THE AUTHOR WOULD LIKE TO THANK Dr. Brian Hafler and Dr. Douglas Brash for their time<br />
and enthusiasm about their research.<br />
18 Yale Scientific Magazine September 2023 www.yalescientific.org
Biomedical Engineering<br />
FOCUS<br />
COVID-19<br />
NASAL<br />
SPRAY<br />
Could an Inhalable Vaccine<br />
Replace a Shot?<br />
BY EVELYN JIANG<br />
ART BY SONIA JIN<br />
Traditional vaccines, such as those developed against smallpox and tetanus, have<br />
relied upon the introduction of weakened or inactivated pathogens into the<br />
body to stimulate the immune system, effectively priming it to recognize and<br />
counteract these pathogens in the future. For several decades, however, scientists<br />
have pursued an ambitious mission to harness the untapped potential of messenger<br />
RNA (mRNA) as a replacement for the pathogens in vaccines. By introducing<br />
mRNA, a small piece of genetic material that instructs cells to produce part of a<br />
pathogen, the vaccines would theoretically trigger an immune response without<br />
causing disease. Scientists envisioned mRNA vaccines harnessing the body’s own<br />
cellular machinery to combat pathogens. Their collective efforts, spanning years of<br />
research, pushed mRNA vaccine technology to the brink of reality.<br />
Then came the COVID-19 pandemic, a crisis of unprecedented proportions that<br />
necessitated a rapid global response. In a mere eleven months, Pfizer/BioNTech<br />
produced the first mRNA vaccine to ever achieve full FDA approval for use<br />
in the United States. As of September 2023, over eighty percent of the U.S.<br />
population has received at least one dose of an mRNA COVID-19 vaccine,<br />
fundamentally altering the pandemic’s trajectory and saving millions of lives<br />
in the U.S. alone. Yet the quest for innovation continues. In a study recently<br />
published in Science Translational Medicine, a team of Yale scientists ventured<br />
into a new frontier in vaccinology: the development of a nasally administered<br />
COVID-19 mRNA vaccine using nanoparticles.<br />
www.yalescientific.org<br />
September 2023 Yale Scientific Magazine 19
FOCUS<br />
Biomedical Engineering<br />
Coronavirus disease (COVID-19) is an infectious disease caused by the SARS-COV-2 virus.<br />
IMAGE COURTESY OF DAVIAN HO<br />
The Promise and Pitfalls of Respiratory<br />
Delivery<br />
Current intramuscular mRNA vaccines,<br />
typically injected into the upper arm,<br />
excel at activating immune defenses in<br />
the bloodstream, but they are not as<br />
effective in rallying protective responses<br />
in the upper airway and lungs. Thus, for<br />
a viral respiratory illness like COVID-19,<br />
the allure of an inhalable mucosal vaccine<br />
stems from its geographical advantage.<br />
When a viruses enter the body through<br />
the nasal route, the respiratory mucosa<br />
(the lining of the respiratory tract)<br />
becomes the primary battleground for<br />
early encounters. Notably, the Omicron<br />
variant has been recorded in higher<br />
concentrations in the lungs than in the<br />
rest of the body. According to Benjamin<br />
Goldman-Israelow, an assistant professor<br />
of internal medicine at the Yale School<br />
of Medicine and one of the authors of<br />
the paper, mucosal vaccines are better<br />
designed to engage the immune system<br />
precisely at this entry site, enhancing<br />
the body’s ability to mount a swift and<br />
targeted response there.<br />
The effectiveness of the oral polio<br />
vaccine, which played a significant role<br />
in the global effort to eradicate polio,<br />
is grounded in the same principle.<br />
Following ingestion, the vaccine induces<br />
a strengthening of immune defenses<br />
within the virus’ favored environment—<br />
the gastrointestinal tract. This localized<br />
approach minimizes the delay associated<br />
with the migration of immune defenses<br />
from the bloodstream to the environment<br />
of interest, thereby reducing the<br />
window of vulnerability and bolstering<br />
protection against invading pathogens.<br />
While the promise of inhalable<br />
vaccines is compelling, it is not without<br />
its challenges. Only one mucosal vaccine<br />
currently exists to combat pathogens<br />
entering through the nasal route: a nasal<br />
spray comprising of weakened flu viruses<br />
known as FluMist. While this nasal spritz<br />
proves reasonably effective in children—<br />
occasionally even surpassing the<br />
performance of its injected counterpart—<br />
its potency wanes significantly in adults.<br />
This may be because the pre-existing<br />
immunity built up over a lifetime of<br />
influenza exposure can inhibit the<br />
vaccine’s effects before it can establish<br />
new protection, according to Goldman-<br />
Israelow. Thus, developing a mucosal<br />
vaccine tailored for respiratory viruses<br />
presents a unique challenge, and there is<br />
no well-established template to follow.<br />
Mark Saltzman, the Goizueta Foundation<br />
professor of biomedical engineering at Yale<br />
and a senior author of the paper, shared that<br />
there were several fundamental challenges<br />
in devising an effective mucosal vaccine.<br />
The effectiveness of mucosal vaccines<br />
relies heavily on how well they can reach<br />
and activate immune cells in the mucosal<br />
surfaces. To reach cells in the lungs, the<br />
vaccine must be able to overcome physical<br />
barriers, such as cilia and mucus, meant to<br />
prevent debris and pathogens contained in<br />
inhaled air from reaching the lungs’ small<br />
air sacs, or alveoli. Phagocytic cells, which<br />
actively participate in the body’s immune<br />
surveillance by destroying microbes<br />
and debris, introduce another obstacle.<br />
These cells may engulf vaccine particles,<br />
thwarting their intended journey to the site<br />
of action and potentially compromising<br />
the vaccine’s effectiveness.<br />
Finally, respiratory mucosa is<br />
especially prone to producing unwanted<br />
immune reactions. While current<br />
mRNA vaccines employ small fat-based<br />
capsules called lipid nanoparticles<br />
(LNPs) as their delivery vehicles, these<br />
components have been noted to incite<br />
inflammation when administered via<br />
nasal routes. In the development of<br />
nanoparticles tailored for inhalation, the<br />
team would have to maximize mRNA<br />
delivery efficiency while minimizing<br />
detrimental inflammatory responses in<br />
the respiratory tract.<br />
Inhaling Nanoparticles<br />
Polymers are molecules formed<br />
from repeating smaller chemical units<br />
known as monomers. Visualize them as<br />
molecular chains built from identical<br />
building blocks repeated in succession,<br />
much like LEGO bricks assembling into<br />
a chain. The Saltzman group designs and<br />
tests incredibly tiny nanoparticles made<br />
20 Yale Scientific Magazine September 2023 www.yalescientific.org
Biomedical Engineering<br />
FOCUS<br />
from polymers for drug and gene delivery<br />
to treat cancers and other diseases.<br />
When the COVID-19 pandemic struck<br />
in 2019, Saltzman began thinking about<br />
how this technology could be applied to<br />
inhalable vaccines. He drew inspiration<br />
from the work of Akiko Iwasaki, the<br />
Sterling professor of immunobiology at<br />
Yale and a senior author on the study,<br />
who is a leading expert on the mucosal<br />
immune response.<br />
In 2020, Saltzman’s lab began<br />
working on this project and produced<br />
biodegradable polymers, called<br />
poly(amine-co-ester) (PACE), which can<br />
form so-called “polyplexes” with mRNA.<br />
The PACE polymers represent a thirdgeneration<br />
polymer-based delivery<br />
system for nucleic acids like mRNA,<br />
distinct from the lipid nanoparticles<br />
(LNPs) commonly used in vaccines.<br />
The conventional approach in the field<br />
has involved employing hydrophobic,<br />
or water-resistant, polymers, which<br />
have proven somewhat successful in<br />
other drugs for delivering nucleic acids.<br />
However, these early polymers were<br />
prone to becoming positively charged<br />
and associating with negatively charged<br />
nucleic acids. Administration of these<br />
agents could inactivate enzymes,<br />
exhibit general toxicity, and affect cell<br />
membranes. “The positively charged<br />
particles just weren’t well-tolerated in<br />
tissues,” Saltzman said.<br />
During the development of the PACE<br />
polymers, his team took a different<br />
approach. The researchers alternated or<br />
substituted some of the positively charged<br />
(cationic) groups with hydrophobic groups.<br />
This design delicately balanced two forces<br />
holding the polymer-nucleic acid complex<br />
together: hydrophobic and electrostatic<br />
interactions. The hydrophobic component<br />
was situated inside the complex, while<br />
a mild positive charge resided on the<br />
outer surface. The researchers postulated<br />
that reducing the charge density within<br />
the polymer structure would enhance<br />
tolerability and minimize potential side<br />
effects. This breakthrough allowed them to<br />
create a versatile family of PACE materials<br />
compatible with various types of nucleic<br />
acids. The researchers found they could<br />
fine-tune the polymer’s hydrophobicity<br />
and charge based on the specific contents<br />
and objectives of their delivery system.<br />
www.yalescientific.org<br />
Translating Success<br />
The researchers tested the ability of the<br />
PACE-mRNA polyplex delivery system<br />
to induce cell-type-specific mRNA<br />
expression in the lungs, which would<br />
indicate that the system was effective<br />
at precisely delivering the nucleic<br />
acids to lung cells. Using PACE-mRNA<br />
polyplexes in mice, they were able to<br />
show that the mRNA was primarily<br />
incorporated in epithelial cells lining<br />
the airways and antigen-presenting cells<br />
in the lungs, which capture, process,<br />
and present components of foreign<br />
molecules to other immune cells to<br />
initiate further responses. The delivery<br />
system was successfully used for multiple<br />
doses without causing significant<br />
inflammation or immune reactions.<br />
To explore the practical applications<br />
of the delivery system, the researchers<br />
then engineered an inhalable mRNA<br />
vaccine encoding the spike protein of<br />
SARS-CoV-2, the virus responsible for<br />
COVID-19. “With the PACE-delivered<br />
mRNA, we were able to see the induction<br />
of immune cellular responses within the<br />
respiratory tract, as well as in systemic<br />
circulation,” Goldman-Israelow said.<br />
The intranasal vaccination prompted<br />
the production of circulating CD8+ T<br />
cells specific to the viral antigen, which<br />
serves as a rapid response team, ready to<br />
track down and destroy virus-infected<br />
cells anywhere in the body.<br />
In the lymph nodes, the vaccine<br />
stimulated the formation of germinal<br />
centers, which are specialized areas<br />
where immune cells undergo intense<br />
training and maturation. This training<br />
process resulted in the expansion of<br />
ABOUT THE AUTHOR<br />
memory B cells, which “remember”<br />
the virus’ unique features, enabling<br />
the immune system to recognize and<br />
neutralize it more effectively upon<br />
future encounters.<br />
The researchers found that the<br />
vaccine also led to the production of<br />
antibody-secreting cells (ASCs), another<br />
critical group of immune cells. ASCs<br />
are responsible for manufacturing<br />
antibodies, which are proteins that<br />
can specifically target and disable the<br />
virus. The combined action of memory<br />
B cells and ASCs enhances the body’s<br />
ability to fend off the virus. Collectively,<br />
these findings illustrate the practical<br />
applicability of PACE polyplexes for<br />
delivering mRNA therapeutics to<br />
the lungs.<br />
Future Steps<br />
Since most individuals have already either<br />
contracted SARS-CoV-2 or received an<br />
mRNA COVID-19 vaccine, the focus is now<br />
on providing booster shots that can keep up<br />
with new variants. According to Saltzman,<br />
this plays to the nasal vaccine’s strengths.<br />
“The beauty of the whole thing is that you<br />
wouldn’t have to change the delivery system;<br />
just exchange the mRNA,” Saltzman said.<br />
Goldman-Israelow, who is also a<br />
practicing physician, shared a similar<br />
perspective. “Looking more long-term,<br />
we know that vaccine hesitancy plays a big<br />
role… If we can get intranasal booster-type<br />
vaccines going, especially for respiratory<br />
illnesses, these will enhance protection<br />
and reduce transmission.” ■<br />
EVELYN JIANG<br />
EVELYN JIANG is a sophomore in Morse College majoring in neuroscience. In addition to writing for<br />
the <strong>YSM</strong>, she works at Yale’s Alzheimer’s Disease Research Unit and the Koleske Lab.<br />
THE AUTHOR WOULD LIKE TO THANK Dr. Mark Saltzman and Dr. Benjamin Goldman-Israelow for<br />
their time and enthusiasm in sharing their research.<br />
FURTHER READING<br />
Suberi, A., Grun, M. K., Mao, T., Israelow, B., Reschke, M., Grundler, J., Akhtar, L., Lee, T., Shin, K., Piotrowski-<br />
Daspit, A. S., Homer, R. J., Iwasaki, A., Suh, H., & Saltzman, W. M. (2023). Polymer nanoparticles deliver<br />
mRNA to the lung for mucosal vaccination. Science Translational Medicine, 15(709). https://doi.<br />
org/10.1126/scitranslmed.abq0603<br />
September 2023 Yale Scientific Magazine 21
FOCUS<br />
Astronomy Computational Biology<br />
VENUS' SKINCARE<br />
ROUTINE<br />
How the Planet Maintains Its Youth<br />
BY CINDY MEI AND DAVID GAETANO<br />
ART BY KARA TAO<br />
22 Yale Scientific Magazine September 2023 www.yalescientific.org
Astronomy<br />
FOCUS<br />
Beneath the endless search for the<br />
perfect skincare routine is a desire<br />
to maintain our youth against the<br />
ravages of time. Yet despite the wealth<br />
of commercially available aloe creams<br />
and collagen powders, the march of<br />
age inevitably slows the skin renewal<br />
process, leaving wrinkles and rough, dry<br />
skin. Likewise, the history and age of a<br />
planet can be deciphered from its surface<br />
by, for instance, dating the oldest rocks<br />
and crystals in its bedrock. But what if<br />
a planet’s surface appears much younger<br />
than its actual age?<br />
Venus, the second planet from the sun,<br />
is estimated to be 4.5 billion years old. It<br />
is theorized that the planet was named<br />
after the Roman goddess of beauty due<br />
to its dazzling brightness in the night<br />
sky. However, Venus has another claim<br />
to its name: its youthful appearance. The<br />
planet’s surface is less than one billion<br />
years old, which is young considering<br />
the long history of the geophysical<br />
time scale. According to a recent paper<br />
published in Nature Astronomy, the<br />
secret to Venus’ strikingly young surface<br />
may lie in volcanic events triggered by<br />
early energetic collisions.<br />
These interplanetary collisions have<br />
always fascinated Simone Marchi, a<br />
planetary scientist at the Southwest<br />
Research Institute (SwRI), who teamed<br />
up with Yale geophysicist Jun Korenaga<br />
and SwRI Sagan Fellow Raluca Rufu to<br />
investigate the effects of early collisions<br />
on Venus’ surface. “Venus comes with its<br />
own mystery and there are a lot of things<br />
that we don't know,” Marchi said. “So I<br />
thought, maybe there is something we<br />
can say about Venus by studying these<br />
early processes.”<br />
Are Collisions The New Collagen?<br />
Imagine an object just short of the<br />
mass of the moon colliding with the<br />
surface of Venus. This is the scale at<br />
which high-velocity collisions occur<br />
on Venus’ surface. When such objects<br />
collide with planets at this scale, it<br />
adds to the surface in a process called<br />
accretion. The team’s research suggests<br />
that late accretion events—the buildup<br />
of new matter in and throughout a<br />
planet—greatly contributed to Venus'<br />
overall geological makeup.<br />
Earlier projects conducted by<br />
Marchi and colleagues examined the<br />
consequences of these large-scale<br />
impacts on Mars and Earth, but Marchi<br />
had something different in mind for<br />
Venus. To understand the effect of<br />
late accretions on Venus, Marchi was<br />
interested in studying the planet through<br />
the lens of geophysics—the study of a<br />
planet’s structure and atmosphere. In<br />
doing so, the team could figure out how<br />
Venus’ volcanic activity, which appeared<br />
to play a major part in its youthful surface,<br />
was linked to the collisions. “Processes<br />
like [volcanism] are connected to the<br />
geophysics of the planet, so that gives us<br />
the motivation to try to understand how<br />
this early energetic event could affect<br />
the geophysical evolution of the planet,”<br />
Marchi said, referring to the collisions<br />
that produced late accretions. His work<br />
on Venus explored the relationship<br />
between these late accretion events and<br />
the planet’s prolonged volcanic activity,<br />
particularly noting that the connection<br />
between these two phenomena lies in<br />
Venus’ superheated core.<br />
Hot To The Core<br />
Venus has the most volcanoes out of<br />
all planets in our solar system. Through<br />
simulations, the researchers were able to<br />
draw some important conclusions that<br />
alter how we think about the relationship<br />
between a planet’s geological makeup<br />
and planetary accretion.<br />
The team found that the early highvelocity<br />
collisions not only created a<br />
magma ocean on Venus’ surface, but also<br />
led to a dramatic heating of the planet’s<br />
core. Furthermore, due to the insulating<br />
nature of Venus’ surface, the planet’s<br />
super-heated core could remain at very<br />
high temperatures. This possibility is<br />
particularly intriguing because it differs<br />
from Earth, where the presence of<br />
plate tectonics cools down the planet’s<br />
interior very efficiently. Venus, however,<br />
lacks tectonic plates, creating a different<br />
geological composition.<br />
When choosing a model, the<br />
researchers assumed stagnant lid<br />
convection on Venus, meaning these<br />
tectonic plates were completely absent.<br />
Their results of simulating stagnant<br />
lid convection starting from highvelocity<br />
impacts on Venus suggest that<br />
the planet’s core remains super-heated,<br />
which helped sustain volcanism for<br />
billions of years. Geological features<br />
such as vast volcanic plains and volcano<br />
domes found on Venus are the result of<br />
these conditions that can all be traced<br />
back to late-accretion events which<br />
heated up the core in the first place.<br />
Venus’ youthful appearance is thus the<br />
culmination of these features, perceived<br />
as a result of the constant magma flow<br />
that smooths the surface over time.<br />
While there have been hypotheses<br />
about Venus’ youthful surface before,<br />
none have attempted to explain it through<br />
the planet’s internal core temperature<br />
and dynamics. “Simone was interested in<br />
combining [these] very short-time scale<br />
impact dynamics with long-time scale<br />
metal dynamics,” Korenaga said.<br />
What About Earth?<br />
Like Earth, Venus is a terrestrial<br />
planet, and is often regarded as Earth’s<br />
“sister planet” due to their similarities<br />
in size and orbit around the Sun. Why,<br />
then, did Earth’s surface fail to fight the<br />
passage of time? By comparing these<br />
www.yalescientific.org<br />
September 2023 Yale Scientific Magazine 23
FOCUS<br />
Astronomy<br />
findings to the relatively well-known<br />
composition of Earth, it is plausible to<br />
conclude that Earth, unlike Venus, did<br />
not experience late accretion events that<br />
affected its core temperature to such a<br />
great extent.<br />
While Earth’s large volume of<br />
surface water broke down the crust<br />
and uppermost mantle of the planet to<br />
form tectonic plates, Venus is closer to<br />
the Sun than the Earth, causing Venus<br />
to rapidly lose surface water through<br />
evaporation. This geophysical difference<br />
is significant, as plate tectonics reduce<br />
internal heat. In addition, the researchers<br />
ran a simulation and found that the mean<br />
impact velocities of late accretions on<br />
Venus were larger than those of Earth.<br />
In other words, small celestial bodies<br />
called planetesimals hit Venus harder<br />
and faster. The lower-velocity impacts<br />
on Earth would lead to less core heating<br />
and an inability to sustain the long-lived<br />
volcanic activity seen on Venus. These<br />
key differences are what lends the ‘planet<br />
of beauty’ its distinct, youthful surface.<br />
Future Directions<br />
Marchi and Korenaga hope to use their<br />
model to make predictions and further<br />
explain the mystery of Venus. “This<br />
difference in late accretion by itself may<br />
not explain all the differences [between<br />
Earth and Venus], but it may help to<br />
push it towards the right direction,”<br />
Korenaga said. The collaboration with<br />
Korenaga, who has studied the origin<br />
of life on terrestrial planets for over a<br />
decade, highlights a key link between<br />
late accretion and the early history of<br />
planets. As it did for Venus, late accretion<br />
played a significant role in Earth's early<br />
history and has a lasting impact on its<br />
present surface features, contributing<br />
substantially to the geological record<br />
of the planet. Thus, understanding<br />
late accretions has other far-reaching<br />
implications for related projects.<br />
According to Marchi, these energetic<br />
events could drastically alter the<br />
chemistry of the atmosphere. For<br />
example, large-scale impacts can lead<br />
to the heating of the crust, generating<br />
a hydrothermal system that could serve<br />
as a possible reservoir for microbes to<br />
ABOUT THE<br />
AUTHORS<br />
PHOTOGRAPHY BY MIRANDA SELIN<br />
The members of Jun Korenaga’s lab: from left to right, (top row) Brianna Fernandez, Darius Modirrousta-<br />
Galian, Amy Ferrick, Jun Korrenaga; (bottom row) Steph Larson, Meng Guo, Coral Chen<br />
thrive. “We strive to understand whether<br />
or not these early impacts could have<br />
had anything to do with the origin of life<br />
on Earth,” Marchi said.<br />
Much of Korenaga’s work in the<br />
past has focused on early Earth and<br />
investigating the geophysical catalysts<br />
for life. “The role of late accretion is<br />
important to discuss generally, for<br />
how you can build a habitable planet,”<br />
Korenaga said. He argues that late-stage<br />
cosmic collisions have a large impact on<br />
whether or not a planet can produce life.<br />
In particular, this research helps us better<br />
understand the geological makeup and<br />
formation of planets, a key ingredient for<br />
a given planet's potential to sustain life.<br />
As a planetary scientist, Marchi is<br />
also involved in space missions and is<br />
currently one of the leaders of the Lucy<br />
Mission, a NASA space probe with<br />
the goal of reaching Trojan asteroids<br />
near Jupiter. Recently, there has been<br />
a revival of interest in Venus in space<br />
exploration. NASA selected two future<br />
space missions to explore Venus in the<br />
coming decade, and the European Space<br />
Union has proposed its own mission.<br />
For next steps, the authors hope to<br />
build off of this work and potentially<br />
explore the geophysics of Earth and<br />
Mars, which could hold more mysteries<br />
of their own. “The work for Venus is<br />
definitely not done,” Marchi said. “But<br />
we'll try to push the new idea forward<br />
to make predictions and try to test that<br />
as much as possible—with new missions<br />
as well.” ■<br />
CINDY MEI<br />
DAVID GAETANO<br />
CINDY MEI is a junior in Grace Hopper studying neuroscience. In addition to writing for <strong>YSM</strong>, she serves<br />
as vice president on the Junior Class Council and Yale Math Competitions. She also conducts epilepsy<br />
and Tourette’s syndrome research at the Yale School of Medicine..<br />
DAVID GAETANO is a sophomore in Ezra Stiles studying Mechanical Engineering. In addition to writing<br />
for <strong>YSM</strong>, he is involved in the Yale Undergraduate Aerospace Association.<br />
THE AUTHORS WOULD LIKE TO THANK Simone Marchi and Jun Korenaga for their time and<br />
enthusiasm about their research.<br />
FURTHER READING:<br />
Marchi, S., Walker, R.J., & Canup, R.M. (2020). A compositionally heterogeneous martian mantle due to<br />
late accretion. Science Advances, 6 (7), doi: 10.1126/sciadv.aay2338<br />
24 Yale Scientific Magazine September 2023 www.yalescientific.org
AN<br />
EEL-ECTRIFYING<br />
INVENTION<br />
NEW DROPLET BATTERY COULD POWER<br />
MINI BIO-INTEGRATED DEVICES<br />
Chemical Biology<br />
FEATURE<br />
All the devices you own right now—<br />
whether it be your computer, phone,<br />
or the TV on which you watch your<br />
favorite shows—would be useless without<br />
one essential component: a battery. As<br />
technology has improved, batteries have<br />
gotten more lightweight and hidden. But<br />
while they are small enough to operate our<br />
phones and TVs, they aren’t small enough<br />
for bio-integrated devices—technology that<br />
can stimulate our cells.<br />
When a premature baby is born, their<br />
whole body is covered in wires and sticky<br />
tape to measure temperature, blood pressure,<br />
respiratory rate, and heart rate. These wires<br />
and tape frustrate both the baby and mother,<br />
limiting their ability to interact and move.<br />
Using a bio-integrated device would allow<br />
them to avoid all this trouble, but currently,<br />
bio-integrated devices don’t have a power<br />
source that can operate at the microscopic<br />
scale and still simulate human tissue.<br />
University of Oxford researchers Yujia<br />
Zhang and Linna Zhou from the Hagan<br />
Bayley lab group have developed a miniature<br />
battery capable of altering the activity of<br />
human nerve cells. These researchers were<br />
inspired by nature and took a cue from<br />
ocean life: their device mimics electric eels<br />
by using internal ions to generate electricity.<br />
Electric eels have been intensely studied<br />
over the years. In fact, Zhang was inspired by<br />
a paper that studied the energy mechanism<br />
of the eels. In it, Thomas B. H. Schroeder,<br />
Anirvan Guha, and Michael Mayer developed<br />
a large-scale hydrogen power source using<br />
that same mechanism. Zhang and his team<br />
had a simple thought: “Maybe we can shrink<br />
this down via a droplet technique.”<br />
The miniature power source they<br />
envisioned came to life using a chain of five<br />
nanoliter-sized droplets of a conductive<br />
hydrogel (a 3D network of polymer<br />
chains that contain a large quantity of<br />
absorbed water). For comparison, one<br />
strand of human hair is 80,000 to 100,000<br />
nanometers wide.<br />
Each droplet has a slightly different<br />
composition, which creates a salt<br />
concentration gradient. At first, the droplets<br />
are separated from their neighbors by a<br />
membrane made of lipids which prevents<br />
ions from flowing between the droplets.<br />
But when the structure is cooled, it changes<br />
the medium, and the power of the structure<br />
is activated. When the droplets on the ends<br />
of this chain are connected to electrodes,<br />
their energy is released and transformed<br />
into electricity. Electricity then enables the<br />
hydrogel structure to act as a power source<br />
for external components.<br />
Living cells could also be attached to this<br />
device, which means that their activity<br />
would be impacted by the ionic current.<br />
When the power source is “turned on”<br />
(by cooling the structure), the neurons<br />
are able to “talk” to each other via<br />
calcium signaling.<br />
Their five-droplet units were<br />
only the beginning. By combining<br />
twenty of these five-droplet<br />
units in series, Zhang’s team was<br />
able to illuminate a two-volt LED<br />
light. In the future, the team hopes to use a<br />
droplet printer to produce droplet networks<br />
made up of thousands of power units. With<br />
that amount of power, they can run biointegrated<br />
devices long term.<br />
“The major goal of this synthetic tissue<br />
project is to be able to interface with<br />
real tissues, creating a network between<br />
synthetic ones and biological ones,” Zhang<br />
said. “This [project] is only one puzzle<br />
piece of the whole puzzle.”<br />
In this project, Zhang’s team was able<br />
to stimulate neurons, but they are already<br />
working on stimulating heart tissues in a<br />
way that allows them to create a network of<br />
synthetic and real cells. Their end goal is to<br />
have a multifunctional interface to various<br />
tissues and organs, not just an interface for<br />
neurons. Through a full-body interface, the<br />
researchers would be able to control the<br />
communication of different types of cells,<br />
which will allow scientists to study cell<br />
development and tissue regeneration.<br />
Zhang says his team owes the majority of<br />
its success to its breadth of expertise—their<br />
research involves engineering, chemistry,<br />
and biology. “It is very important for young<br />
scientists to understand the interdisciplinary<br />
nature of experiments, “ Zhang said. “It<br />
isn’t enough to just be an expert in one<br />
field, but a lot of different fields. Only by<br />
combining these fields together can we<br />
truly solve these problems.”<br />
In the future, their new battery could<br />
have a notable impact on devices such as<br />
bio-hybrid interfaces, microrobots, and<br />
implants for improved disease monitoring,<br />
targeted drug delivery, and more. Zhang<br />
hopes that his team’s research will make<br />
these ideas one step closer to reality. ■<br />
BY SHARNA SAHA | ART BY SOFIA JIN<br />
www.yalescientific.org<br />
September 2023 Yale Scientific Magazine 25
FEATURE<br />
Archaeology<br />
THE BRICK OF LIFE<br />
Ancient DNA Reveals Hidden Secrets<br />
in a 2900-year-old Clay Brick<br />
BY ILORA ROY<br />
ART BY MIRANDA SELIN<br />
Imagine walking down an old pathway, strewn with weathered<br />
stones, when you trip on a loose brick. You might be irritated,<br />
but what if those mundane little bricks were more than an<br />
annoyance? What if they hid the secrets of civilizations from<br />
thousands of years ago?<br />
During a series of excavations beginning in 1949 led by Max<br />
Mallowan and other British archeologists, a clay brick was<br />
excavated from the ancient city of Kalhu in Mesopotamia, today<br />
known as Nimrud, Iraq. The brick dates back 2,900 years to 879<br />
B.C., which was during the reign of King Ashurnasirpal II over<br />
the Neo-Assyrian Empire from 883 B.C. to 859 B.C. The Neo-<br />
Assyrian empire was remarkable for many reasons, including<br />
advancements in astronomy and mathematics, as well as<br />
impressive architecture. The excavated “brick of life” was once<br />
part of King Ashrunasipal’s palace. It is a sundried concoction<br />
of straw, animal dung, and mud from the Tigris River, with an<br />
Akkadian inscription on it that reads: “the property of the palace<br />
of Ashurnasirpal, king of Assyria.”<br />
The unassuming brick, which had broken horizontally into two<br />
pieces, was then donated to the National Museum of Denmark<br />
in 1958. Later, a group of scientists digitized it, splitting the<br />
brick again, but this time vertically. However, this split wasn’t<br />
troublesome—in fact, it was quite the opposite, as it allowed<br />
researchers to study uncontaminated material inside the brick.<br />
In an interview with Troels Pank Arbøll, Assistant Professor of<br />
Assyriology at the University of Copenhagen and a key figure<br />
in the project, he conveyed optimism and enthusiasm for the<br />
potential discoveries on the horizon. The brick is a portal to a<br />
bygone era that invites us to peer into the archives of history.<br />
The researchers took five separate samples from the cracks<br />
in the clay and analyzed them to produce the aDNA—ancient<br />
DNA—of thirty-four taxonomic groups of plants. Each crack<br />
offered a look into the past. This was done through two cuttingedge<br />
sequencing techniques—a process in molecular biology that<br />
involves determining the precise order of the building blocks<br />
of DNA molecules. The first technique is amplicon sequencing,<br />
which selectively amplifies and sequences specific DNA regions<br />
within a larger genetic sample. The second is metagenomic<br />
shotgun sequencing, which enables the exploration of all genes<br />
across all organisms within a complex sample. These precise and<br />
critical sequencing techniques were vital tools in uncovering the<br />
truths behind the fragile aDNA, which is highly degraded due<br />
to its age. The pursuit of these invaluable insights demanded<br />
patience and unwavering commitment.<br />
Scientists are certain that the DNA is uncontaminated since all<br />
of the samples came from the core of the brick, which has not<br />
been exposed to the outside world since the brick was first created<br />
roughly 2900 years ago. Such certainty is remarkable, as it is rare<br />
for aDNA so old to remain untouched. The species found in the<br />
clay brick include specimens correlated with different types of<br />
Iraqi flora, carrots, parsnips, celery, birch, and more. This aDNA<br />
has bridged gaps in our understanding of the Neo-Assyrian<br />
Empire, serving as a portal into the past.<br />
The brick’s aDNA can also help us to look into the future.<br />
By studying the species in such bricks, researchers may notice<br />
differences and similarities between plants from 2900 years<br />
ago and today. These observations will be important to combat<br />
climate change and help our ecosystem because the past<br />
furnishes researchers with invaluable insights into patterns of<br />
biodiversity loss, teaching us how to mitigate similar perils in<br />
the present day. “The goal would be, in due time, to establish<br />
a dataset of historical biodiversity for reference in current<br />
discussions,” Abrøll said. Examining how ecosystems responded<br />
and adapted in the past can shed light on their resilience and<br />
capacity for recovery in the future.<br />
Beyond advancing our understanding of the ecosystem and our<br />
history, this discovery shows the necessity of interdisciplinary<br />
collaboration. When discussing the possible future for research<br />
around endemic plants in Iraq, Arbøll emphasizes the importance<br />
of collaborating with scientists when researching the history of<br />
these plants. “It is our hope that future studies with more concrete<br />
identifications of ancient DNA might help speed this process up,”<br />
Arbøll said.<br />
So, the next time you encounter a tricky loose brick, consider<br />
the possibility that it might harbor a treasure trove of secrets,<br />
bridging the chasm between antiquity and modernity—a<br />
testament to the unyielding wonders concealed within the world’s<br />
most unassuming corners. ■<br />
26 Yale Scientific Magazine September 2023 www.yalescientific.org
Neuroscience<br />
FOCUS<br />
A Scent-sational<br />
Memory Boost<br />
How Smelling New Scents During<br />
Sleep May Improve Your Memory<br />
BY KENNY CHENG<br />
ART BY ANGELIQUE ROUEN<br />
Crying over a textbook with exams approaching? Can’t<br />
remember the name of that familiar face? The solution may<br />
lie right under your nose—literally.<br />
In a paper published in the Frontiers of Neuroscience, scientists at<br />
the University of California, Irvine (UCI) found that the cognitive<br />
capacity of older adults increased by a whopping 226 percent<br />
when exposed to a different fragrance every night for six months.<br />
Participants of the study simply placed one of seven different essential<br />
oil scents—eucalyptus, lavender, lemon, orange, peppermint, rose,<br />
and rosemary—into a two-hour diffuser each night to reap the<br />
benefits of improved memory. By stimulating neural networks of the<br />
brain with uncommon odors, it was found that the critical memory<br />
pathways of participants were significantly strengthened along with<br />
memory test scores when compared to the control group.<br />
The association between olfactory stimulation and memory has,<br />
in fact, long been established. For example, young adults who have<br />
trained as sommeliers—and therefore are exposed to dozens of wine<br />
odors every day for months—have thicker brains, specifically in the<br />
entorhinal cortex, an area heavily associated with memory capacity.<br />
Another more recent example is the loss of smell as a result of<br />
COVID-19, which can lead to symptoms of poor memory and ‘brain<br />
fog.’ However, the most remarkable example of the relationship<br />
between smell and memory was demonstrated in South Korea where<br />
dementia patients were exposed to forty odors twice a day, resulting<br />
in a three hundred percent magnitude of memory improvement<br />
compared to other dementia patients who didn’t receive this olfactory<br />
stimulation. So what sets the new UCI study apart?<br />
“We’ve automated the process of olfactory enrichment. After<br />
all, it’s unrealistic for patients to open forty bottles of perfume<br />
and sniff each one every day,” said Michael Leon, Professor of<br />
Neurobiology and Behavior at UCI and a co-author of the paper.<br />
“The advantage of using odors at night is that odors can’t wake<br />
you up. Unlike other sensory systems, the olfactory system<br />
doesn’t go through the thalamus, which is connected to the sleep<br />
centers. You can wake somebody up with a noise or bright light or<br />
by touching them, but you can’t wake somebody up with an odor,<br />
even if the odor is of frying bacon.”<br />
While many people may be familiar<br />
with aromatherapy, in which scents<br />
from one essential oil are used for<br />
therapeutic purposes, “olfactory<br />
enrichment” is distinct. The benefit<br />
doesn’t come from one particular scent—<br />
instead, olfactory enrichment is reliant on long-term exposure to a<br />
multitude of new and distinct scents to stimulate the nervous system.<br />
Leon’s team has now constructed a diffuser device capable<br />
of automatically delivering forty odors at night, aptly named<br />
MemoryAir. But wouldn’t the novelty of these scents wear off?<br />
“No,” Leon answered. “It turns out that people are not very good<br />
at identifying odors, let alone forty of them. So people will get that<br />
novelty experience even if they do it over a course of many months.<br />
Although, we do have plans to introduce new odors in the future.”<br />
From their research, Leon and his partners are optimistic about the<br />
wider implications of their work on treatment for dementia patients<br />
and for society at large.<br />
“We believe everybody in the modern affluent world is chronically<br />
deprived of olfactory stimulation. In fact, if you take a deep breath<br />
now, you probably wouldn’t smell anything at all,” Leon said. “The<br />
human brain evolved at the time when there were plenty of odors<br />
around. So, the good thing about being in the affluent world is that<br />
you don’t have a lot of odors. The bad thing about not having a lot of<br />
odors is that your brain is deteriorating or at least not fulfilling its full<br />
potential because it doesn’t get that stimulation.”<br />
With the long-term effects of odorless modern life remaining a<br />
mystery, Leon argues that olfactory enrichment may be a simple<br />
and inexpensive tool for the prevention and treatment of dementia.<br />
But first, this technology will need to be tested on a larger pool of<br />
patients—particularly those diagnosed with dementia. Additionally,<br />
there were concerns about the small size of the study group since<br />
some participants were removed to limit confounding factors that<br />
the COVID-19 pandemic may have introduced.<br />
Even so, the next time you’re grinding out for your next exam<br />
past midnight, remember that novel scents—both pleasant and<br />
unpleasant—may boost your memory. ■<br />
www.yalescientific.org<br />
September 2023 Yale Scientific Magazine 27
FEATURE Physics<br />
THE<br />
PHONON PHENOMENON<br />
Harnessing Photon-Phonon Coupling to Advance Quantum Computing<br />
BY ANNLI ZHU AND LEA PAPA<br />
Communication is a natural part of<br />
life. Humans talk, birds chirp, and<br />
even trees interact through their root<br />
networks. To maintain this essential aspect<br />
of life, we adapt our methods to overcome<br />
communication challenges: a team meeting<br />
that once had to be held in a boardroom<br />
can now be effectively held on a Zoom<br />
call. For quantum computers—a system<br />
that looks to advance past the capabilities<br />
of classical computing—communication<br />
occurs by leveraging quantum particles and<br />
their properties, components of sub-atomic<br />
interactions that have historically been<br />
challenging to harness.<br />
Recently, physicist Mo Li and his colleagues<br />
at the University of Washington were able to<br />
overcome one such challenge: dealing with<br />
unpredictable photon emitters. They achieved<br />
this by designing a deterministic emitter —one<br />
where they can determine where the photon<br />
is emitted—and in doing so, they discovered<br />
that their emitter produced a strong<br />
interaction between two important quantum<br />
quasiparticles: photons and phonons. Now, Li<br />
is hopeful that further research can use this<br />
interaction to advance communication in<br />
quantum computing systems and overcome<br />
some challenges in the field.<br />
In classical computers, information<br />
is stored in bits: either 0 or 1. Quantum<br />
computers use quantum bits—<br />
called “qubits”—which can exist in a<br />
“superposition” state of being both 0 and 1<br />
at the same time, like Schrödinger’s cat. This<br />
allows them to consider many possibilities<br />
simultaneously. Through a process called<br />
entanglement, qubits can be connected<br />
in a way such that the state of one qubit<br />
instantly influences the state of another,<br />
no matter how far apart they are, enabling<br />
quantum computers to perform complex<br />
calculations literally faster than light can<br />
travel. This means quantum computers<br />
have the potential to revolutionize fields<br />
like cryptography, drug discovery, and<br />
more. However, because they are highly<br />
sensitive to environmental conditions,<br />
require extremely low temperatures, and<br />
use extensive space, they are expensive to<br />
build and difficult to scale.<br />
Although many subatomic particles<br />
can be used for quantum computers,<br />
scientists prefer to use photons—tiny,<br />
massless particles of light—to transmit<br />
quantum information because they travel<br />
at, well, the speed of light. But photons are<br />
difficult to reliably produce, control, and<br />
capture. Traditional methods of photon<br />
generation—through so-called “quantum<br />
emitters”—involve taking advantage of<br />
defects in various atomic lattices, which<br />
are patterned arrays of bound atoms.<br />
However, these defects often emit photons<br />
unpredictably, which is undesirable for<br />
highly precise quantum computers.<br />
To address this problem, the team of<br />
scientists at the University of Washington<br />
set out to build a “deterministic” quantum<br />
emitter. “We want to engineer it in such a<br />
way that we can say ‘we want an emitter here’<br />
and it indeed emits there,” said Li, Professor<br />
of Electrical & Computer Engineering and<br />
Physics and leader of the research team.<br />
To achieve this goal, the team used two<br />
single-atom layers of tungsten and selenium,<br />
similar to existing quantum emitters. Then,<br />
they draped these layers over hundreds of<br />
nanoscopic pillars, creating tiny bumps in<br />
the 2D lattice that isolated the target regions.<br />
By shining a precise pulse of laser light at an<br />
electron in the material, they were able to free<br />
it for a very short period of time. Each time<br />
an electron returned to its place, it emitted<br />
a single photon encoded with quantum<br />
information—a successful quantum emitter.<br />
Amidst their successes with the<br />
deterministic emitter, Li and his colleagues<br />
noticed something<br />
intriguing in their<br />
data. “The emitter<br />
ideally is supposed<br />
to generate a very<br />
sharp peak in energy<br />
at one wavelength<br />
28 Yale Scientific Magazine September 2023 www.yalescientific.org
Physics<br />
FEATURE<br />
associated with the photon, but when we<br />
looked a little bit closer, there [was] a group of<br />
satellite peaks on the sides, and we wondered<br />
where that [came] from,” Li said.<br />
As they analyzed the data, they came to<br />
an exciting conclusion: phonons—quantum<br />
quasiparticles that are a unit of vibrational<br />
energy—may be responsible for these satellite<br />
peaks. The energy is caused by the vibration<br />
between two atomic layers, and such motion<br />
has been described as “atomic breaths.”<br />
“It’s not uncommon,” Li said. “It’s called<br />
phonon replica, and it appears in other<br />
systems as well, but in our system, it’s very<br />
pronounced.” Normally, the phonon replica<br />
will appear as a group where intensity is<br />
strongest at the shortest wavelengths, and then<br />
rapidly decays. In their system, however, the<br />
phonon replica is the strongest in the middle<br />
and weaker at the side peaks. This indicated<br />
that the “coupling”—the phonon interaction<br />
with the emitter or the mechanical vibration<br />
between the two atomic layers—is very strong<br />
and overwhelms the emission that has no<br />
interaction with the phonon, creating this<br />
irregular array of peaks.<br />
“Every time [the emitter] takes a breath, it<br />
emits one phonon and that phonon is taken<br />
out of one photon. So, the optical photon that<br />
is emitted is reducing energy by exactly one<br />
phonon,” Li said.<br />
Phonons have been historically difficult<br />
to leverage for quantum computation, but<br />
they have great potential when coupled with<br />
photons. While photons are very popular for<br />
communication due to their speed, storing<br />
information on them is difficult. On the<br />
other hand, because phonons vibrate at a<br />
much lower frequency, future advancements<br />
in quantum technology may allow them to<br />
live much longer than photons, acting as<br />
temporary information storage. This is where<br />
the phonon-photon interaction comes in.<br />
“They can exchange information. When<br />
you want to stall the quantum information<br />
there, you convert them into phonons. The<br />
information will stay there; a little while<br />
later you can come back and read it out. But<br />
if you’re ready to send that information out<br />
of the system to another system, then you<br />
convert it into a photon,” Li said.<br />
Leveraging this deterministic emitter<br />
and strong coupling activity could advance<br />
quantum computing systems by improving<br />
inter-computer communication. Excited, Li<br />
shared some of his ideas for future research<br />
that may be able to translate his findings into<br />
something specifically useful for quantum<br />
computing. One idea is the possibility of<br />
building a similar system with more than one<br />
emitter. But what would this achieve?<br />
“Because the phonons are localized, if the<br />
two emitters are close enough, the vibrations<br />
will interact with each other. This is a way to<br />
make two emitters talk to each other,” Li said.<br />
Unlike photons, which don’t couple with<br />
each other, the phonon’s properties suggest<br />
a possibility of coordinating two or three<br />
emitters—by coupling the phonons instead.<br />
Since the photons cannot interact, they can<br />
instead “talk through” the phonons before<br />
flying off to their destinations. If an effective<br />
two- or three-emitter system is achieved,<br />
it could revolutionize the way quantum<br />
computers communicate with each other.<br />
This theory may also be able to<br />
address the issue of scaling in quantum<br />
computers—something that has greatly<br />
challenged researchers in the field. While<br />
larger computers with more qubits are<br />
more powerful in completing tasks, they<br />
are difficult and expensive to build and<br />
maintain. Currently, IBM’s 433-qubit<br />
computer is the largest in the world. “But<br />
[433 qubits] isn’t enough to do any realistic<br />
quantum computing,” Li said. “Maybe some<br />
toy models, but nothing to the level of what<br />
quantum computers promise in theory.”<br />
Instead, just like in classical computers,<br />
tasks would benefit from being modularized,<br />
split up to be completed in parallel by<br />
multiple smaller computers. But while<br />
classical computers can operate at room<br />
temperature, most quantum computers<br />
require extremely low-temperature and lownoise<br />
environments in order to facilitate<br />
the precise manipulation of qubits. On the<br />
other hand, any communication between<br />
computers, achieved by sending photons<br />
through fiber-optic cables, happens at a<br />
frequency five orders of magnitude higher<br />
than that at which quantum calculations are<br />
performed. “We need something to bridge<br />
this energy gap,” Li said, “This is where our<br />
emitters have their potential.”<br />
The team’s breakthrough in photonphonon<br />
coupling would allow these spatially<br />
separate quantum computers to solve the<br />
problem of effective transduction: converting<br />
signals between mediums without loss of<br />
information. This gives researchers the<br />
potential to build scalable, modularized<br />
quantum computing networks.<br />
“The holy grail of this research would<br />
be to make two, maybe three, or more,<br />
emitters talk to each other,” Li said. “This<br />
will allow us to realize the full potential of<br />
quantum computing.” ■<br />
ART BY ANNLI ZHU<br />
www.yalescientific.org<br />
September 2023 Yale Scientific Magazine 29
FEATURE<br />
Geochemistry<br />
BARNACLE BREADCRUMBS<br />
FINDING LOST MALAYSIAN AIRLINES FLIGHT MH370<br />
BY MADELEINE POPOFSKY<br />
ART BY KARA TAO<br />
It was March 8, 2014—a day like any<br />
other—when 239 people took to the<br />
skies aboard Malaysia Airlines Flight<br />
370 on their way from Kuala Lumpur to<br />
Beijing. Some were going home after a<br />
long time away. Others were world-famous<br />
calligraphers returning from a business trip.<br />
Some may have been scared of flying and<br />
clutched the armrests as the plane took off.<br />
But after that fateful day, none of those 239<br />
people, nor the plane they sailed away on,<br />
were ever seen again. And despite years of<br />
intensive searching—using everything from<br />
submarines to sonar imaging—their final<br />
resting place has yet to be discovered.<br />
Over a year later, on July 29, 2015, Gregory S.<br />
Herbert, Associate Professor of Paleobiology<br />
at the University of South Florida, was<br />
watching the news and saw that a piece of<br />
the missing aircraft’s wing, called a flaperon,<br />
had been found on Réunion Island. Herbert<br />
instantly knew that he had to make some<br />
calls. A clue that could unlock the location<br />
of the lost plane had been unearthed, and he<br />
was uniquely qualified to decode it.<br />
Herbert’s background lies in stable isotope<br />
geochemistry; specifically, he decodes ocean<br />
temperatures from barnacle shells. If a<br />
drifting object has barnacles, scientists can<br />
potentially use these temperatures to track<br />
its path through the ocean. And barnacles,<br />
clinging to the flaperon, were clearly visible<br />
on the TV screen. “I knew immediately that<br />
there were sea surface temperatures recorded<br />
in those barnacles,” Herbert said. “Some<br />
of the barnacles were fairly large, and they<br />
could have recorded the whole drift.”<br />
Herbert tried to contact the French<br />
authorities, who had possession of the<br />
flaperon, and the Malaysian officials, who<br />
were running the investigation. Both<br />
attempts failed. However, Herbert was<br />
not deterred, and the third time proved to<br />
be the charm: the Australian authorities,<br />
who helped coordinate the search since<br />
the plane’s likely final location nears their<br />
territory, enthusiastically agreed to look over<br />
his proposal.<br />
Based on satellite data, the plane’s final<br />
resting place is thought to lie somewhere<br />
in the Indian Ocean along the seventh arc,<br />
between latitudes twenty and forty degrees<br />
S. However, this is an extremely large area<br />
that the plane may not even be in. But with<br />
the technique Herbert and his colleagues<br />
have developed, scientists can say for sure<br />
whether the plane is in the seventh arc, and<br />
can pinpoint its location to a smaller and<br />
more easily searchable area.<br />
Barnacles grow in daily layers, similar to<br />
the rings trees produce every year. Each of<br />
these layers encodes chemical data about<br />
their surroundings at the time of growth.<br />
Different isotopes of oxygen are deposited<br />
at different sea surface temperatures, with<br />
a known relationship between their ratio<br />
and the temperature. Scientists can analyze<br />
this ratio through δ 18 O values to determine<br />
the temperature the barnacles experienced<br />
each day, and match that data with different<br />
temperature currents that run through<br />
the Indian Ocean. Other scientists had<br />
previously jumped on this information to<br />
produce temperature and location models<br />
for the aircraft, but in their rush to complete<br />
the work, they failed to use experimental<br />
controls, leading to large uncertainties in<br />
their results.<br />
Despite these apparent problems with the<br />
previous studies, Herbert had a difficult time<br />
securing funding for his study. In the end,<br />
the Florida Aquarium decided to fund his<br />
research, as it could also be used to benefit<br />
sea turtles. Sick sea turtles will float for weeks<br />
and thus develop barnacles on their normally<br />
clear front flippers. If these barnacles could<br />
be traced, scientists could begin to identify<br />
areas where sea turtles tend to get sick. Thus,<br />
a method was born that could both trace a<br />
missing plane and track sick turtles.<br />
This new technique, created by Herbert<br />
and his colleagues, had two unique and vital<br />
components that set it apart from previous<br />
attempts. The project was the first to create<br />
an experimentally derived equation for the<br />
particular species of barnacle (cosmopolitan<br />
30 Yale Scientific Magazine September 2023 www.yalescientific.org
Geochemistry<br />
FEATURE<br />
stalked barnacle, Lepas anatifera) that was<br />
attached to the flaperon. Barnacles were<br />
placed into tanks, stained with a marker<br />
(a fluorescent dye) that showed divisions<br />
between layers, and subjected to slowly<br />
changing temperatures. The scientists then<br />
anesthetized the barnacles and analyzed<br />
their layers for δ 18 O content. Finally, they<br />
created an equation that relates temperature<br />
and δ 18 O content.<br />
The second innovation centered around<br />
what to do with that temperature data.<br />
While temperature does vary throughout<br />
the ocean, there are large bands that are<br />
the same temperature throughout. “Just<br />
knowing that first temperature doesn’t tell<br />
you where the plane is; you have to do a lot<br />
more work,” Herbert said. In other words,<br />
each new temperature recorded is needed<br />
to narrow down the<br />
search; knowing just the first temperature<br />
recorded by the barnacle is not enough.<br />
This extra work involved developing<br />
a modeling simulation using known sea<br />
surface temperatures and other data such as<br />
current velocity that is consistently recorded<br />
across the oceans. The simulation allowed<br />
the researchers to cast virtual flaperons<br />
adrift from various starting points, and then<br />
statistically analyze their routes to determine<br />
the most likely path each barnacle on each<br />
flaperon took based on its temperature data.<br />
Herbert and others on the team applied<br />
this technique using previously published<br />
data for one of the smaller barnacles found<br />
clinging to the flaperon. First, they calculated<br />
the barnacle’s age at each layer through an<br />
experimentally derived equation relating<br />
barnacle size to age. “We measured the<br />
size of the barnacle at each sample, at each<br />
temperature,” Herbert said.<br />
They then cast 50,000 virtual flaperons<br />
adrift in different places along the band of<br />
the ocean defined by the barnacle’s earliest<br />
temperature value. Then, they compared<br />
the temperature data these virtual<br />
flaperons experienced with the actual<br />
temperature data from the barnacle<br />
using a method called dynamic<br />
time warping. Eventually, this<br />
eliminated all but one virtual<br />
flaperon, which was the only<br />
one to end near where it was<br />
actually found: in waters<br />
near Réunion Island.<br />
However, the<br />
timeline for<br />
applying this new<br />
and promising<br />
t e c h n i q u e<br />
will have<br />
to wait<br />
on the<br />
French government, which has custody of<br />
the largest barnacles. These are the only<br />
barnacles that could have recorded the<br />
entire drift of the flaperon. “I have a feeling<br />
that they're still sitting on these shells<br />
because there were three French scientists<br />
who worked on them, and their work was<br />
very rushed, and they did not get any sort<br />
of a conclusive result,” Herbert said. The<br />
French government likely wants to keep the<br />
samples until the foundational work that<br />
will allow for conclusive results has been<br />
completed. Thus, it is possible the French<br />
government will release the barnacles in<br />
light of these new findings.<br />
In the meantime, the next step is to improve<br />
the model and equations. “I just wanted to<br />
demonstrate how to do the method first,”<br />
Herbert said. To begin, Herbert and others<br />
have already started work on a more accurate<br />
barnacle age model, since shell size is not the<br />
most accurate predictor. They also want to<br />
improve the flaperon motion model used;<br />
for example, accounting for the fact that a<br />
flaperon does not behave like an idealized<br />
buoy, and instead drifts slightly left. Finally,<br />
the researchers need to perform a sensitivity<br />
analysis. This involves running the model<br />
thousands more times with different errors<br />
factored in to see how dramatically these<br />
errors change the results. This work would<br />
take up to a year, even if the larger barnacles<br />
from the French were provided immediately.<br />
However, hopes are high. Of the five<br />
drifters in the simulation that best matched<br />
the known barnacle’s path, four of them<br />
started in the same location, tightly<br />
clustered together. “We’re not just looking<br />
for a single temperature, we’re looking<br />
for a sequence, a very unique sequence of<br />
temperatures. And there aren’t that many<br />
drift origins, and drift pathways, that could<br />
possibly be consistent with that,” Herbert<br />
said. When asked if the plane would ever be<br />
found, Herbert didn’t hesitate.<br />
“Yes,” he said. ■<br />
www.yalescientific.org<br />
September 2023 Yale Scientific Magazine 31
FEATURE<br />
Astrophysics<br />
TWINKLE, TWINKLE,<br />
GIANT STAR<br />
INVESTIGATING WHY MASSIVE STARS FLICKER<br />
BY DIYA NAIK AND ROBIN TSAI<br />
ART BY LUNA AGUILAR<br />
A dying star shimmers and twinkles<br />
as its inner core, formerly a churning<br />
dynamo, sputters out its final breaths.<br />
Nuclear fusion combines atomic nuclei<br />
to birth new heavy elements that<br />
will soon occupy the cosmos. And<br />
then it happens: a fiery explosion,<br />
where the insides of the star<br />
fly everywhere. Left in the<br />
aftermath of the chaos is either a<br />
neutron star or a black hole.<br />
For astrophysicists back<br />
home on Earth, understanding<br />
the characteristics of these<br />
explosive dying stars is the key<br />
to understanding our past and<br />
current universe—everything from star<br />
formation to galaxy evolution to the very<br />
beginnings of our universe. But to really<br />
understand the characteristics of these<br />
stars, we need to start from the bellies<br />
of the beasts: the processes within these<br />
stars. This is done with asteroseismology.<br />
Asteroseismology applies the techniques<br />
of seismology—which uses waves to<br />
understand the interior of the Earth—<br />
to stars. In order to understand what is<br />
left behind after a star dies, you have to<br />
understand its internal<br />
structure back when it<br />
was still alive. This<br />
structure includes<br />
everything from<br />
the eddies<br />
of rotating<br />
plasma that<br />
twist deep<br />
within the<br />
furnace of the<br />
core to the light<br />
and heat that<br />
jostles from its<br />
surface.<br />
So, how do we peer<br />
inside stars? We must turn an eye to their<br />
light. How bright is it? Does it change<br />
over time? Is it high-energy like an X-ray<br />
or is it low-energy like a radio wave? The<br />
answers to each question reveal a wealth<br />
of information on the energy released by<br />
the star: its temperature, its stability, and<br />
much more. By making predictions for<br />
what light outputs should look like, we<br />
can test the actual light of stars against<br />
our assumptions to see how well our<br />
physics match up with the real world.<br />
Any discrepancies reveal new avenues for<br />
future scientific exploration.<br />
For astrophysics postdoctoral researcher<br />
Evan Anders and his research group at<br />
Northwestern University, one particular<br />
real-world signal caught their attention:<br />
red noise. Red noise is a ubiquitous, lowfrequency<br />
twinkling in the light signals<br />
from massive, stable stars—much like the<br />
static on a blank TV channel. These stars<br />
are called main sequence stars, a category<br />
which most stars, like our Sun, belong to.<br />
Real-life observations about a star allow<br />
researchers to eliminate possibilities and<br />
therefore gain a more precise<br />
understanding of the<br />
internal mechanics<br />
of the star.<br />
“We hoped this<br />
red noise was<br />
gravity waves<br />
because gravity<br />
32 Yale Scientific Magazine September 2023 www.yalescientific.org
Astrophysics<br />
FEATURE<br />
waves give you a lot of information about<br />
the structure of the star,” Anders said.<br />
“They’re telling you about how big the core<br />
is.” Gaining a more lucid understanding<br />
of the inside of the star, such as the size<br />
of its core, allows us to better understand<br />
the energy that the star releases and define<br />
the pressure it uses to create new elements.<br />
While scientists do have simple models for<br />
this task, these models fail to align with<br />
real-world data. They need a more detailed<br />
model built on empirical evidence, and<br />
gravity waves could provide that evidence.<br />
But what is a gravity wave? We can see<br />
an example here on Earth: storms and<br />
winds push the ocean waters up, creating<br />
waves. But the Earth’s gravity resists this<br />
upward movement, causing the wave to be<br />
pulled downwards, creating an oscillatory<br />
displacement. A similar thing happens<br />
in stars. “[In gravity waves], you<br />
displace this [fluid] from where<br />
it wants to be and gravity<br />
pushes it back down—and<br />
then you get this wiggly<br />
pattern,” Anders said.<br />
Deep within the<br />
centers of stars,<br />
nuclear fusion<br />
of hydrogen into<br />
helium creates an<br />
inferno, generating<br />
immense amounts of<br />
bright hot plasma that<br />
have nowhere to go but<br />
out. When this material<br />
reaches the very edge of the core, it breaks<br />
free in a fourteen-day-long ripple before<br />
sinking back into the heart of the star. As<br />
fusion continues, the core roils with these<br />
cycles of hot to cool to hot to cool, churning<br />
gravity waves across the core. These waves<br />
propagate through the rest of the star,<br />
reverberating at different frequencies like<br />
guitar strings.<br />
Modeling these waves with a<br />
supercomputer is extremely difficult, but<br />
Anders and his team designed a clever<br />
way of mimicking the red noise. Thanks<br />
to earlier models by one of the researchers<br />
(Northwestern fluid dynamicist and<br />
assistant professor Daniel Lecaonet),<br />
Anders and his team had previous<br />
models of wave formation and<br />
propagation that could be tweaked<br />
for higher accuracy.<br />
Anders’ simulations can be<br />
compared to a music studio—<br />
recording raw music before passing<br />
it through a filter to create a specific<br />
effect. Anders’ ‘filter’ consists of<br />
code that translates the waves created<br />
by core convection—showing what they<br />
would look like distorted by the rest of the<br />
star outside of the core—and thus what the<br />
waves actually look like leaving the star<br />
and reaching our eyes as light.<br />
The scientists created their filter based<br />
on a simpler model of how stars worked.<br />
The idea was that it would be easy to<br />
predict what the light signals from this<br />
rudimentary filter should look like. If<br />
the output of the program matched their<br />
predicted output, the scientists could<br />
go back and painstakingly craft<br />
a more advanced filter with all<br />
the physical complexities of<br />
the star—a filter with enough<br />
refinement to see unique<br />
signals such as the red noise.<br />
Their basic filter demo<br />
passed with flying colors,<br />
and it was then time for<br />
the real deal. Anders' team<br />
set to work crafting a more<br />
accurate filter, one that<br />
captured the intricacies of the<br />
star's mechanics outside of the<br />
core, reflecting the true polyphony<br />
of physical effects of a star rather than just<br />
a few. If the glimmer of signal leaving the<br />
filter matches the hum of the red noise,<br />
then gravity waves are the source of the<br />
red noise.<br />
However, when Anders combined the<br />
waves generated by convection and the<br />
echo of gravity waves outside the core, the<br />
difference between the output signal and<br />
red noise was glaring. Their simulation<br />
revealed that gravity waves are far too<br />
muted to match the high-amplitude signal<br />
of red noise. But for scientists, a definitive<br />
no is just as exciting as a definitive yes.<br />
Knowing what the red noise isn’t brings<br />
astronomers closer to understanding<br />
what it really is. The next theory<br />
in line is that the red noise<br />
comes from motions closer<br />
to the star's surface.<br />
Anders has two directions<br />
he might take his future<br />
research. He might want to<br />
take the elaborate programs<br />
he developed here to further<br />
explore the waves within stars.<br />
“We use the amplitude of the<br />
wave to learn something about the<br />
process that’s driving it,” Anders said. The<br />
second direction, on the other hand, would<br />
be refining his simulation further. “[We<br />
add] rotation, because stars, well, rotate,”<br />
Anders said.<br />
There are several possibilities for<br />
improvement in the team’s research. They<br />
did not factor in the rotations that affect<br />
the cycles of plasma, nor did they include<br />
the effects of magnetic fields. However,<br />
their work still proves to be an important<br />
step in understanding the inner workings<br />
of stars. Listening to asteroseismology’s<br />
music of the spheres brings us closer to<br />
understanding the massive stars that<br />
churn in our universe. ■<br />
www.yalescientific.org<br />
September 2023 Yale Scientific Magazine 33
UNDERGRADUATE PROFILE<br />
HARPER LOWREY<br />
BY NYLA MARCOTT YC ’24<br />
Harper Lowrey (YC ’24)<br />
first became fascinated<br />
by the wide-ranging<br />
implications of science after reading a<br />
book with her mom called Lab Girl as a<br />
child. “My mom read it and said that she could never work<br />
in science, while I was like, ‘Ooh that sounds fun,’” Lowrey said. “[I<br />
find inspiration] when things get rough, but there are cool results<br />
that come out of the struggle.”<br />
Lowrey, who grew up in Colorado, always enjoyed exploring the<br />
outdoors and first became interested in pursuing a career in research<br />
after participating in a summer camp at the University of Colorado<br />
Boulder. During the camp, she stayed at the university’s research<br />
station and had the opportunity to learn from mycologists—<br />
scientists who study fungi. “[I was] so enamored by the concept of<br />
being able to study the world, which I think was probably the start<br />
that led me into academic science,” Lowrey said.<br />
Lowrey was determined to continue studying biology in<br />
college. When applying to Yale, she was selected for the Hahn<br />
Scholars program, which seeks to recruit high-achieving students<br />
with extensive STEM research experience. As a first-year, Lowrey<br />
joined the Gendron Lab, where she investigated how plant<br />
circadian clocks use post-translational regulation to control the<br />
amount of protein active in a system at one time.<br />
Although conducting research could have been an intimidating<br />
experience, members of the Gendron Lab made sure that Lowrey<br />
felt like a valued member of the group. “I was immediately treated<br />
like somebody who had ideas that were important, which I think<br />
is a really great environment in science, instead of like, ‘You need<br />
to sit there and be quiet and learn from other people.’ I have really<br />
benefited from being a part of the team and working towards our<br />
common goal,” Lowrey said.<br />
PHOTOGRAPHY BY LIANA TALPINS<br />
Harper Lowrey’s plants on which she researches circadian clocks.<br />
Lowrey’s research in the Gendron Lab is focused on<br />
understanding how the growth restrictor gene, CFH1, is<br />
controlled by a plant’s circadian clock. Circadian clocks allow<br />
plants to predict changes in their environments on a 24-hour<br />
cycle and are responsible for the regulation of a variety of<br />
functions essential for survival, such as growth and defense.<br />
In the absence of CFH1, plants develop very long hypocotyls,<br />
the first seedling stems that occur after germination. Lowrey’s<br />
research has helped uncover CFH1’s role in controlling<br />
hypocotyl growth in Arabidopsis thaliana, a common plant<br />
model species. A manuscript that includes Lowrey’s research<br />
has been submitted for peer review and will likely lead to further<br />
research regarding how CFH1 works in other plant species.<br />
In addition to conducting research at Yale, Lowrey participated<br />
in molecular biology research on transgene silencing—the loss<br />
of gene expression transferred from one organism to another—<br />
at the Donald Danforth Plant Science Center in Missouri. In the<br />
summer after her junior year, she also conducted research at the<br />
Cold Spring Harbor Laboratory on argonaute proteins, which<br />
are integral in RNA interference. Both experiences provided<br />
her with the opportunity to meet other plant biologists and<br />
to contribute to postdoctoral research projects. “You learn a<br />
lot when you are new to a place—getting new techniques or<br />
doing different things—and I feel like it also helps increase my<br />
scientific confidence,” Lowrey said.<br />
While Lowrey’s research is designed to increase knowledge<br />
of plant physiology and is not specifically linked with industry<br />
interests, she recognizes the complexities that arise when<br />
conducting plant biology research more closely tied to industry.<br />
“I do think a lot more thought needs to be about what products<br />
we are trying to produce—especially if we’re talking about<br />
agriculture and products that are going to the market. Just<br />
because something is cost-effective or we will make money from<br />
it is not the only reason to make that kind of thing,” Lowrey said.<br />
In April, Lowrey’s commitment to research earned her the<br />
prestigious Goldwater Scholarship. She is now working to<br />
complete her major in Molecular, Cellular, and Developmental<br />
Biology, as well as certificates in French and Education<br />
Studies. After graduation, she plans to pursue a Ph.D. in plant<br />
molecular biology. As Lowrey continues to study science, she<br />
finds enjoyment in building a deeper understanding of the<br />
world and hopes to help others do the same by running her<br />
own lab and mentoring the next generation of scientists.<br />
“Long term, my goal is academia,” Lowrey said. “I am<br />
really interested in thinking about what kinds of things are<br />
important in how we’re teaching and policies around teaching.<br />
It is important that college professors know how to teach [...]<br />
in ways that are equitable and effective.” ■<br />
34 Yale Scientific Magazine September 2023 www.yalescientific.org
ALUMNI PROFILE<br />
ILANA YURKIEWICZ<br />
YC ’10<br />
BY HIMANI PATTISAM<br />
Writer, Copy Editor, News Editor, Features Editor, and<br />
eventually Editor-in-Chief: during her time at Yale, Ilana<br />
Yurkiewicz (YC ’10) wore many hats at the Yale Scientific<br />
Magazine (<strong>YSM</strong>). But she didn’t leave science writing behind after<br />
graduation. Even now, as a clinical assistant professor of primary<br />
care and population health at Stanford, Yurkiewicz combines her<br />
passions for writing and medicine in her work as a science journalist,<br />
author, and physician. “<strong>YSM</strong> was where I got my start. I always had<br />
an itch to write and take complex scientific concepts and make them<br />
understandable for people,” she said.<br />
As an undergraduate, Yurkiewicz explored the depths of a liberal<br />
arts education, taking philosophy courses and writing seminars in<br />
addition to a typical pre-med workload of chemistry and biology. She<br />
also conducted genomics research in a bioinformatics lab studying<br />
DNA testing for genetic conditions, which sparked her interest in<br />
bioethics and the intersection between science and the humanities.<br />
She graduated in 2010 with a degree in Molecular, Cellular, and<br />
Developmental Biology.<br />
After Yale, Yurkiewicz took a year off and completed the American<br />
Association for the Advancement of Science (AAAS) Mass Media<br />
Science and Engineering Fellowship in science journalism, where<br />
she worked as a science and health reporter at The News & Observer<br />
in Raleigh, North Carolina. “I had a couple of stories on the front<br />
page, and it was always really exciting to see that [...] It’s always been<br />
really important to me that we bridge the gap between hospitals and<br />
laboratories with everyday lives,” Yurkiewicz said. Following her<br />
passion for bioethics, Yurkiewicz also interned for the Presidential<br />
Commission for the Study of Bioethical <strong>Issue</strong>s before attending<br />
Harvard Medical School.<br />
During her time at Harvard, Yurkiewicz continued writing, creating<br />
a blog column called “Unofficial Prognosis” for Scientific American<br />
where she shared reflections on her medical school experiences with<br />
hundreds of thousands of readers. “I had full editorial freedom to<br />
write about whatever I thought was interesting,” Yurkiewicz said. She<br />
then moved across the country to complete her residency in internal<br />
medicine, followed by a fellowship in oncology and hematology, at<br />
Stanford. Now, as a faculty member<br />
there, she co-directs a primary care<br />
center for cancer survivors.<br />
In July, Yurkiewicz published<br />
her debut book, Fragmented:<br />
A Doctor’s Quest to Piece<br />
Together American Health<br />
Care, which she worked on<br />
for two years. Fragmented<br />
was inspired by her own<br />
experiences as a physician<br />
navigating the healthcare<br />
system and making decisions<br />
based on fragmented medical<br />
www.yalescientific.org<br />
PHOTOGRAPHY BY HANNAH HAN<br />
Ilana Yurkiewicz (YC ’10), a physician at Stanford and the former Editorin-Chief<br />
of the Yale Scientific Magazine, holds her recently published novel,<br />
Fragmented: A Doctor’s Quest to Piece Together American Health Care.<br />
records. “I found myself always working in a partially blindfolded state<br />
to stitch together patient stories,” Yurkiewicz said. She first became<br />
interested in the topic after delving into the history of converting paper<br />
patient notes into a digital format, and she began to investigate how<br />
medical records can vanish when patients transfer between medical<br />
facilities. Fragmented zooms out to investigate barriers beyond recordkeeping<br />
that fracture a patient’s story into pieces, and she explores how<br />
doctors and patients can piece them back together.<br />
In the future, Yurkiewicz hopes to write a second book chronicling<br />
her experiences as a physician providing primary care to cancer<br />
survivors. She plans to focus on the ‘hard questions’ of life, death,<br />
and serious illness that cancer patients must grapple with throughout<br />
their diagnosis and treatment journeys. “My patients often ask me<br />
to write stories to share their experiences and advocate for them,”<br />
Yurkiewicz said. She explained that she takes great care to convey<br />
empathy and compassion and to protect confidentiality while<br />
exploring complex issues that her patients face.<br />
For Yurkiewicz, writing journalistic pieces with nuance and depth<br />
has the power to impact a large audience. Through her work, she aims<br />
to empower people to advocate for more comprehensive solutions to<br />
reform the healthcare system. “Illness is a great equalizer, and my focus<br />
[is] to write for everyone—physicians, policymakers, patients, and<br />
the general public,” Yurkiewicz said. But she also hopes to someday<br />
explore a new genre. “I wrote stories for fun at Yale,” she said. Her ‘pipe<br />
dream’ is to return to those roots and write a science fiction novel,<br />
grounding her stories in real science.<br />
Although she has pursued her passion for science writing alongside<br />
medicine, patient care has always been Yurkiewicz’s highest priority,<br />
and she has periodically taken breaks from writing to focus on honing<br />
her medical practice. “There are ebbs and flows in the busy doctor life,<br />
but science writing always comes back,” she said. Balancing multiple<br />
professional hats as a physician and journalist is difficult, but Yurkiewicz<br />
emphasizes that it is possible. Her advice for students interested in both:<br />
“Pursuing a career in science journalism and medicine is a harder path,<br />
but if you really care about something, you will do it well.” ■<br />
September 2023 Yale Scientific Magazine 35
WRITING FOR THEIR LIVES<br />
BY KEYA BAJAJ<br />
SCIENCE<br />
IN<br />
IMAGE COURTESY OF SMITHSONIAN INSTITUTION ARCHIVES<br />
It is late 1937, and the American Society for the Control of Cancer convenes for a press<br />
dinner under the dim chandeliers of the Harvard Club. All the invitees are welcome to<br />
attend, except one: America’s premier medical journalist, Jane Stafford. To seat a woman<br />
at the table would have “considerably changed the character of the dinner,” admitted the<br />
organization’s publicity director; besides, the University Club didn’t allow women entry<br />
anyway. Thrumming below the frenzied fever of twentieth-century scientific exploration<br />
was a culture of leaving women out of a conversation they pioneered, when they were the<br />
ones deconstructing scientific jargon.<br />
In her newly released book Writing for Their Lives, historian Marcel Chotkowski<br />
LaFollette chronicles the untold story of eight female science journalists who made science<br />
intelligible to the average reader and put its latest advances on the front page, but who were<br />
themselves omitted from the headlines. These women disseminated scientific discoveries<br />
through published stories and columns, breaking both the news and the professional<br />
paradigms of the time.<br />
“Historians of science have tended to write about scientists, not those who wrote about<br />
science,” LaFollette writes. In her novel, LaFollette attempts to lift the “historical fog”<br />
that has hidden the pioneering efforts of these women. In 1921, Science Service, a small<br />
Washington, D.C.-based science news organization, gave a group of dedicated female<br />
science journalists their footing. Emphasizing meritocracy instead of gender, Science<br />
Service boasted a female majority in its cohort of editorial staff writers; Jane Stafford was<br />
just one of them.<br />
Jane Stafford’s wide news sweep encompassed everything from schizophrenia to public<br />
health epidemics, with a particular focus on cancer. Her work involved expository pieces,<br />
like one in 1928 contesting the nicotine-free contents of a tobacco brand. She brought a<br />
potent mixture of journalistic strengths to the newsroom: the ability to decipher volumes<br />
of dense scientific literature, a dexterity with language (specifically in her allusions to<br />
Classical myths and iconography), and an ability to speak truth to power.<br />
In 1945, Science Service reported news of the atomic bomb, explaining the science<br />
behind history as it unfolded in real time. While other news outlets succumbed to<br />
sensationalism, the female journalists at Science Service collaborated to present a more<br />
measured report of the Hiroshima-Nagasaki events. Martha Morrow reported on the<br />
physics; Jane Stafford explored radiation and physiology; Helen Davis wrote about its<br />
chemistry; and Marjorie Van de Water discussed the bomb’s socio-psychological effects.<br />
As “career women,” they braved both the pressures of the news cycle and the inherent<br />
misogynies of a male-dominated scientific community.<br />
While occasionally dry in its journalistic tone and factually heavy in its ambitious<br />
scope, LaFollette is successful in her detailed account of the hidden figures of scientific<br />
journalism. If it took time for science to leave the confines of laboratories and trickle into<br />
our lives—learning from curbside newsstands, on the taxi radio, and over morning cups<br />
of coffee—Writing for Their Lives shows us that it took far longer to decide who got to tell<br />
those stories. “The paths to success [for female journalists] were riddled with the potholes<br />
of institutionalized bias along with the gaping gullies of entrenched and unapologetic<br />
misogyny,” LaFollette writes.<br />
It would be 1973 before the Harvard Club would open its doors to full-time women<br />
members. By then, Jane Stafford had already established fundamental journalistic<br />
practices, co-founded the National Association of Science Writers, and served as president<br />
of the Women’s National Press Club—all while not being allowed to sit in on dinners. ■<br />
T<br />
S<br />
36 Yale Scientific Magazine September 2023 www.yalescientific.org
"<br />
RACISM IN HEALTH<br />
BY SAMUEL OBIAMA<br />
Half of all medical student respondents did not believe that Black<br />
patients felt pain the way Whites did. So did a lot of practicing<br />
physicians,” a study published in PNAS reported. If asked when<br />
this study was conducted, many might guess sometime in the twentieth<br />
century, or earlier.<br />
The actual year was 2016.<br />
This revelation was just one of the many disturbing findings revealed in<br />
“The Roots of the U.S. Black Maternal Mortality Crisis,” a podcast jointly<br />
produced by Scientific American and Nature in August. The podcast opens<br />
by examining Georgia’s new law that bans abortions after six weeks of<br />
conception, before launching into an explanation of its past precedents and<br />
future ramifications on pregnant Black women.<br />
Historically, unintended pregnancy rates are higher among Black women<br />
compared to White women. Due to income disparities, job insecurity,<br />
and overall underinsurance, Black women have less access to long-acting<br />
reversible contraceptives (LARCs) and must resort to using condoms,<br />
which are a less effective form of contraception. Higher rates of unintended<br />
pregnancy, coupled with increased susceptibility to mistreatment during<br />
childbirth, contribute to the racial disparity in maternal mortality rates: Black<br />
women are three times more likely to die in pregnancy than White women.<br />
The podcast makes a strong effort to show that socioeconomically<br />
THE<br />
disadvantaged Black women are not alone in this phenomenon. Serena<br />
Williams and Shalon Irving, for instance, are both healthy, educated,<br />
affluent women whose obstetrician-gynecologists dismissed their concerns.<br />
Irving visited her doctor multiple times and reported swelling in her right<br />
leg and a weight gain of nine pounds in two weeks. She was ordered to “wait<br />
it out” and died in 2017 due to birth-associated complications caused by<br />
high blood pressure. Williams, on the other hand, told her doctors that she<br />
thought she had a pulmonary embolism. Even though she had experienced<br />
one before, her physician ignored her claim, and she nearly died.<br />
Both of these cases could have been avoided if their own doctors had<br />
listened to them.<br />
Is there any hope left? Since Roe v. Wade was overturned last year, more<br />
SPOTLIGHT<br />
awareness has been raised about this issue than ever before. This increased<br />
public attention may not only help lower the Black maternal mortality rate<br />
but also help reduce the factors that contribute to the issue, such as implicit<br />
racial biases among physicians.<br />
“The Roots of the U.S. Black Maternal Mortality Crisis” integrates<br />
interviews with researchers, historians, and family members of women who<br />
died from mistreatment, providing a holistic view of the Black maternal<br />
mortality crisis. By referencing the complicated, interwoven history of<br />
childbirth and slavery, analyzing existing stereotypes, and hypothesizing how<br />
ever-changing legislation will affect Black women in the U.S., this podcast<br />
calls us to question, analyze, and change our existing healthcare system. ■<br />
IMAGE COURTESY OF RAWPIXEL.COM<br />
www.yalescientific.org<br />
September 2023 Yale Scientific Magazine 37
POINT<br />
The Discovery of a Superheavy<br />
Oxygen Isotope<br />
Since the days of the Manhattan Project, nuclear<br />
physicists have concerned themselves with<br />
the study of certain atomic nuclei known as<br />
“magic nuclei.” Protons and neutrons, also known<br />
as nucleons, occupy shells within the nucleus<br />
corresponding to different energy levels. When<br />
these shells are full, our leading nuclear theory<br />
predicts the resulting isotope to be significantly<br />
more stable than other isotopes of similar mass and<br />
neutron-to-proton ratios.<br />
Magic nuclei are unique because they have a full<br />
shell of either protons or neutrons. Since magic<br />
nuclei were first discovered, scientists have been<br />
able to determine if a given nucleus is “magic” by<br />
counting the number of protons and neutrons.<br />
Specifically, physicists predict that magic nuclei must<br />
contain exactly two, eight, twenty, twenty-eight, fifty,<br />
eighty-two, or 126 protons or neutrons. Following<br />
this pattern, oxygen-28 ( 28 O), the oxygen isotope<br />
consisting of twenty neutrons and eight protons, was<br />
predicted to be “doubly magic,” since it has a magic<br />
number of both protons and neutrons.<br />
Oxygen-16 ( 16 O), in its natural form, has six protons<br />
and six neutrons. To test the stability of 28 O, a team of<br />
physicists with experimental operations based in the<br />
RIKEN Radioactive Isotope Beam Factory in Wako,<br />
Japan, worked to produce the isotope. The generation<br />
and detection of 28 O was a highly technical feat:<br />
researchers shot a high-energy beam of calcium-48<br />
atoms at a beryllium target, producing fluorine-29,<br />
which is only one proton away from the desired 28 O.<br />
The team then propelled the fluorine-29 atoms into a<br />
wall of liquid hydrogen, knocking off the necessary<br />
proton and creating 28 O. Using a specialized detector,<br />
the physicists observed the emission of four neutrons<br />
and a stable oxygen-24 ( 24 O) isotope, indicating that<br />
28 O had in fact been present before decaying into<br />
24 O. To their surprise, however, the decay of 28 O<br />
failed to demonstrate the high stability expected<br />
of a “doubly magic” isotope, raising a host of new<br />
questions about its atomic structure.<br />
Numerous results from the experiment suggested<br />
that, contrary to expectations, 28 O does not have a<br />
full shell of neutrons in its nucleus. The first piece of<br />
evidence was the almost immediate decay of 28 O on<br />
By Ian Gill<br />
a faster timescale than the researchers were able to<br />
measure, indicating that the supposed stability of the<br />
isotope does not hold up experimentally.<br />
The researchers also computed the spectroscopic<br />
factor, a number between zero and one that describes<br />
the stability of the nuclear structure based on how<br />
much the arrangement of nucleons changes when<br />
a proton or neutron is removed. In a nucleus with<br />
full shells, the structure is very rigid, so removing<br />
one nucleon doesn’t cause widespread change in the<br />
arrangement of the surrounding nucleons, resulting<br />
in a high spectroscopic factor. On the other hand, if<br />
the structure of a nucleus is very unstable, removing<br />
one nucleon sets off a cascade of structural changes,<br />
yielding a low spectroscopic factor. Interestingly, the<br />
spectroscopic factor found by the team was much<br />
lower than what would have been expected if 28 O<br />
had a full shell of neutrons.<br />
Based on this data, the team concluded that despite<br />
having the correct number of protons and neutrons to<br />
fill both nuclear shells, some of the neutrons in 28 O<br />
occupy higher energy levels instead, making the isotope<br />
not “doubly magic.” 28 O is not the only exception to the<br />
typical rule for identifying “doubly magic” nuclei: 24 O,<br />
which contains sixteen neutrons and eight protons,<br />
has historically demonstrated the stability that comes<br />
with being “doubly magic.” In light of these results,<br />
physicists are left with two major questions: What<br />
criteria can be used to predict if a nucleus is “doubly<br />
magic?” And why is it that the numeric rule tends to<br />
hold, but has a few select exceptions?<br />
Future experiments aim to gain more context for<br />
the stability of 28 O and to explore how nuclei with<br />
high neutron-to-proton ratios, such as oxygen-30<br />
( 30 O), behave. Through these experiments, scientists<br />
hope to broaden their grasp of the nuclear shell model<br />
as a whole, gaining insight into phenomena taking<br />
place from a scale as small as that of a single isotope,<br />
to the scale of an entire neutron star. Alternatively,<br />
it’s entirely possible that these further investigations<br />
could reveal deep flaws with our current approach<br />
towards the structure of the nucleus, and perhaps<br />
even serve as a starting point for new theories. As for<br />
now, we can only be certain that there is much work<br />
to be done to fully understand “magic nuclei.” ■<br />
COUNTERPOINT<br />
The Heaviest Air in the World<br />
38 Yale Scientific Magazine September 2023 www.yalescientific.org
INTEGRATION<br />
OR<br />
INVASION?<br />
BY ISAIAH ASBED<br />
On my desk sits a brain. Until 1984, it was kept in a<br />
Brown University neuroscience lab. It’s now found<br />
below a wrinkled Scarface poster, illuminated by<br />
LEDs. It’s just a plastic model, and the right side of the medulla<br />
is broken off a little. But regardless of its idiosyncrasies, it’s<br />
a brain. It has a cerebral cortex, tinted pink and indented<br />
by the peaks and valleys of gyri and sulci. At its base is its<br />
cerebellum, darkened by dense collections of cell bodies. It<br />
even has a pineal gland, Descartes’ seat of consciousness,<br />
buried deep within the cerebrum.<br />
And that’s almost enough to make you believe, despite<br />
its literal plasticity, that electrochemical signals are running<br />
around in there, from axon to dendrite, from neuron to<br />
neuron. Because it’s those signals that make a collection of gray<br />
and white matter a brain. An almost entirely self-contained<br />
network of cells that uses electrical messages from our sensory<br />
receptors to conceive of a world both external and internal.<br />
We recognize that this consciousness, granted to us by the<br />
synapses between neurons, is something sacred. And yet,<br />
for millennia, we’ve altered it. When a Tiwanaku shaman,<br />
exploring a river valley deep in ancient Bolivia, came<br />
across a psilocybin mushroom, his dendrites proliferated,<br />
making his nerve networks more intricate than ever before.<br />
Receptors typically bound by serotonin were inundated by<br />
psychedelics, permanently changing both his synapses and<br />
the worlds they created.<br />
But now, we’ve moved beyond chemical alteration.<br />
Perspective can dictate whether we’ve shifted to integration or<br />
invasion. We’ve invited machines into our neural web, and by<br />
doing so, we’ve let them become a part of our consciousness.<br />
Functionally both dendrite and axon, electrode arrays can<br />
not only receive and process information, but also directly<br />
stimulate neighboring neurons through electrical signals,<br />
alternately activating and inhibiting their fellow world creators.<br />
Abilities previously reserved for biological matter have been<br />
ceded to imitations.<br />
Instinct might tell us not to tamper with what we hold sacred.<br />
But we, like that early shaman, can be grateful that we don’t give<br />
PERI<br />
instinct too much power. Because our relationship with these<br />
machines is, for now, more mutualistic than parasitic. Their<br />
integration with our synapses will give us revolutionary<br />
insights into the worlds within that grayish-pink model on<br />
my desk. Research into disorders like epilepsy will develop<br />
faster than ever before, and the brain’s connection with<br />
prosthetic limbs will strengthen dramatically. As long as we<br />
don’t surrender ourselves completely to this technology, the<br />
changes these machines bring can be for the better.<br />
Artist’s Statement:<br />
When I was young, I read the story of John Henry—<br />
the existentialist slave turned railroad worker who<br />
gave his life to prove that even in an age of rapid<br />
industrialization, man was still greater than machine.<br />
When he collapsed from exhaustion, and his victory<br />
over steam power turned pyrrhic, I felt angry. I didn’t<br />
know it then, but that was the birth of an inherently<br />
human distrust for mechanization.<br />
When I grew up, and the stories I encountered began<br />
to evolve, I saw the movie Awakenings, based on the<br />
work of neuroscientist Oliver Sacks. As I watched him<br />
manipulate the neurotransmitters that determine our<br />
responses to stimuli, almost to the point of curing<br />
an incurable form of encephalitis, I felt a growing<br />
attachment to our cells and the signals that produce<br />
conscious thought.<br />
Somewhat predictably, I’ve always had my suspicions<br />
about the brain-machine interface. Reading Song et al.’s<br />
article (pg. 4) on the newest biocompatible electrode<br />
array didn’t change that. But it did make me consider the<br />
conflict between the human instinct to cast off the help<br />
of machines and the human desire for progress. And<br />
now, I’ve started to wonder which impulse’s victory is in<br />
our best interests. ■<br />
METERKARA TAO<br />
ART BY<br />
www.yalescientific.org<br />
September 2023 Yale Scientific Magazine 39
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