YSM Issue 96.4

Yale Scientific 

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

DECEMBER 2023 

VOL. 96 NO. 4 • $6.99 

THE 

FAILURE 

ISSUE

TABLE OF 

VOL. 96 ISSUE NO. 4 

SPECIAL ISSUE 

12 

Rediscovering Cosmic Origins 

David Gaetano 

For centuries, the mysteries of our solar system’s origins have intrigued scientists and thinkers alike. 

In a 1941 edition of the Yale Scientific Magazine, a Yale professor cast doubt on the major theories 

of the time, without raising any of his own. New technology over the past decade, however, has 

made these unanswerable questions now well-understood. 

14 Is Alcohol Use Disorder In Our Genes? 

Matthew Blair & Lea Papa 

Over the last century, alcohol use disorder has been a unique case study of the ‘nature versus 

nurture’ debate. Scientists have long argued about whether the condition is primarily caused by 

the environment, or if it is inherited and can be attributed to our genes. Today, our understanding 

reveals a more complex answer. 

16 The Ticking Clock to Fight Ticks 

Cindy Mei 

Lyme disease, a tick-borne illness that can have dangerous health effects if not detected early, 

has been on the rise since 2000. Despite promising studies highlighting the potential of a Lyme 

disease vaccine appearing over three decades ago, there is still no vaccine available today. Recently, 

researchers have discovered a strategy to develop an “anti-tick” mRNA vaccine that may be able to 

protect against not only Lyme disease, but also other tick-borne illnesses. 

19 Revisiting The "Brilliant Future" of PFAS 

Evelyn Jiang 

Since the 1950s, PFAS—dubbed ‘forever chemicals’—seemed to have a brilliant future ahead, with 

uses in various products like waterproof clothing, non-stick pans, and firefighting foam. However, 

with more evidence suggesting that PFAS is toxic to our environment and bodies, PFAS serves as a 

stark reminder of what can happen when scientific innovation goes unchecked. 

22 Gene Therapy For Parkinson's Disease 

Madeleine Popofsky & Risha Chakraborty 

In 1992, YSM reported on a novel gene therapy for Parkinson’s disease, which has since failed. However, 

decades later, two new approaches show promise in treating this neurodegenerative disease at its 

genetic source. For patients, this could mean a better option than today’s most common treatment, 

Levodopa, which loses effectiveness over time and with more advanced forms of the disease. 

2 Yale Scientific Magazine December 2023 www.yalescientific.org

CONTENTS 

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

4 

6 

8 

9 

25 

34 

LETTER 

TIMELINE 

Q&A 

PROFILES 

FEATURES 

SPECIALS 

Special Issue: Joint Letter from the Editors 

• Alex Dong, Madison Houck, and Sophia Li 

A Brief History of Scientific Failures • Keya Bajaj 

Why Is "Disruptive" Science Dwindling, While "Hype" Language 

Is On The Rise? • Sunny Vuong 

Ammonium Chloride: Fertilizer Ingredient, Pickling Agent… 

Or The Sixth Taste? • Ethan Powell 

Brian Nosek • Nathan Wu 

Marc Abrahams • Mia Gawith 

Stuart Firestein • Kavya Gupta 

Faster Than Lightspeed • Genevieve Kim 

Seawater Squabbles • Brandon Ngo 

This Metal-Free Reaction Contains... Metal • Lawrence Zhao 

From “Not Good Enough” to Nobel Prize Winner • Annli Zhu & Michael Sarullo 

Life on Venus! Actually, No! Actually, Maybe? • William Archacki 

Room Temperature Superconductors? Not So Fast… 

• Yossi Moff & Yamato Takabe 

YSM Archives vs. Today: The Rise of "Thinking Machines" • Ian Gill 

Science in the Spotlight: Hype and Failure • Ximena Leyva Peralta 

Science in the Spotlight: Serendipitous Science • Jamie Seu 

Counterpoint: Reckoning With The Ghosts of YSM’s Past • Samantha Liu 

Perimeter: A New Precipitation • Molly Hill 

www.yalescientific.org 

December 2023 Yale Scientific Magazine 3

Letter from the Editors 

THE FAILURE ISSUE 

Preface: The last magazine of each calendar year is, as per Yale 

Scientific Magazine tradition, a themed special issue. This letter, 

co-written by your outgoing 2023 managing team—Alex Dong, 

Madison Houck, and Sophia Li—examines why we have chosen 

to focus on failure as our central theme. We will also explain how 

each section of this special issue has been modified to cover a 

different aspect of our theme, while highlighting several notable 

articles exclusive to this magazine. We hope you enjoy reading 

Vol. 96 No. 4: The Failure Issue! 

 

As anyone from an undergraduate student to a tenured 

professor could tell you, failure is a natural, necessary part 

of science. The scientific method is predicated on a constant 

cycle of failures and successes that drive experimental work 

forward. Arguably, a failed experiment can be more generative 

than a successful one, yielding new questions and research 

directions. And yet, most major scientific journals exclusively 

publish success stories. These stories are then picked up by 

journalists and communicated to the public, while a long 

history of failed experiments remains obscured from view. It’s 

an open secret—we all know success doesn’t come easy, but we 

don’t seem to want to hear about a series of mistakes without 

groundbreaking innovation to show for it. 

When the 2023 Nobel Prize in Physiology or Medicine was 

announced in October, science journalists began reporting on 

the incredible stories of Katalin Karikó and Drew Weissman. 

Although their contributions to the mRNA COVID-19 vaccine 

have undoubtedly shaped our world today, their work was 

consistently underestimated and disregarded for years until 

the right set of circumstances recently led to a breakthrough 

(pg. 30). Inspired by their story and its subsequent public 

reception, our final issue of the year seeks to examine the 

theme of failure broadly across science and science journalism. 

How do scientists regard failure? How have initial failures led 

to great progress? And how have overhyped innovations fallen 

by the wayside? 

In this spirit, we also asked: How has our own magazine 

failed in the past? The Yale Scientific Magazine (YSM), the 

nation’s oldest collegiate science publication, has existed 

in some form or another for 130 years. It’s easy to evaluate 

the failures of others critically and even to perceive them as 

avenues for growth, but it’s much more difficult to examine 

oneself. This year, as we moved our historical archives from 

our old offices in Welch Hall and 305 Crown Street to the 

Benjamin Franklin College Library, we had the opportunity to 

delve into the evolution of YSM over time. 

Our magazine’s past has included missteps ranging from 

the comical—like the “Troubled Years” where YSM rebranded 

to focus on student affairs rather than science from 1918 to 

1926—to the incredibly serious, like the magazine’s promotion 

of eugenics and other pseudoscientific ideas in the 1900s. 

Ultimately, this is another reason why our managing team felt 

that “The Failure Issue” was so important to create. As our 

magazine continues to grow and change, it is our responsibility 

as young journalists to understand our organization’s past and 

to learn from it. 

 

In this special issue, we have modified our usual sections to 

reflect this endeavor of examining and reflecting upon failure. 

Our “Shorts” section, which has replaced “News,” begins with 

a timeline of notable scientific failures throughout the ages— 

whether that be Aristotle’s disproven theory of spontaneous 

generation in the 4th century BC or the fall of the nowinfamous 

biotech company Theranos (pg. 6). This section then 

presents short profiles of three unconventional scientists: Brian 

Nosek, who studies the reproducibility of new discoveries and 

how to make the research process more transparent (pg. 9); 

Marc Abrahams, who founded a magazine and prize ceremony 

to honor unusual, imaginative, and humorous science (pg. 

10); and Stuart Firestein, who investigates why failure is the 

driving factor behind scientific success (pg. 11). 

For our Full-Lengths section, we went back to YSM’s archives 

and selected decades-old articles to examine how our scientific 

understanding of various subjects has evolved—or been 

subverted—over time. For instance, a YSM article written in 1941 

discredited one hypothesis about the origins of the solar system 

that has, in fact, developed into the theory widely accepted by 

physicists today (pg. 12). In another article, we reflected on a 

Lyme disease vaccine covered by YSM in 1993 with a seemingly 

promising future that was never actualized (pg. 16). 

Our Features section focuses on more contemporary scientific 

discourse and the trial-and-error nature of experimentation. 

For example, a 130-year-old assumption about seawater ion 

distribution was recently debunked (pg. 26), bringing forth a 

need to reevaluate past research that relied on it. Over the past 

three years, there have also been intense back-and-forths in 

science, such as an ongoing debate about life on Venus (pg. 

30) and the multiple attempts—and failures—to create roomtemperature 

superconductors (pg. 32). 

These ideas, decades ago, might have sounded like the stuff 

of science fiction. In our Special Sections, we have included 

a reprint of a 1951 YSM article interrogating the impact 

that intelligent robots may have on society through this lens 

of science fiction (pg. 34). We then wrote a side-by-side 

comparison of those ideas with the very real developments of 

artificial intelligence and machine learning today (pg. 35).

So, what have we learned? Some inventions and innovations were hailed 

as the next big breakthrough, only to fall short of expectations. Other 

discoveries were not given a second glance but turned out to have worldchanging 

impacts. Either way, failure in science is ubiquitous. With the 

benefit of hindsight, it can be easy to discount the striving and the seemingly 

innumerous number of times we’ve barked up the wrong tree. Yet we must 

keep in mind that no experiment will be the “final one” or the “capstone” of a 

field—the work will never be finished. There will always be something more 

to question or explore. 

 

With that, it is now time for us to pass over the reins to the next masthead. 

It has truly been an honor to serve you all as your 2023 YSM Managing 

Team this year. We would like to thank our incredible contributors across all 

five branches—Editorial, Production, Business, Web, and Synapse—without 

whom none of this would have been possible, as well as our 35 masthead 

members for their leadership, initiative, and tenacity. 

We would also like to express our deepest gratitude to the Yale Science 

and Engineering Association and its president, Milton Young, for their 

instrumental guidance and support this year. Finally, thank you, our readers, 

for your continued engagement with YSM—you are the reason we do what 

we do. Here’s to science, to striving, and to failure. 

Sincerely, 

MASTHEAD 

December 2023 VOL. 96 NO. 4 

EDITORIAL BOARD 

Editor-in-Chief 

Managing Editors 

News Editor 

Features Editor 

Special Sections Editor 

Articles Editor 

Online Editors 

Copy Editors 

Scope Editors 

PRODUCTION & DESIGN 

Production Manager 

Layout Editors 

Art Editor 

Cover Artist 

Photography Editor 

BUSINESS 

Co-Publishers 

Operations Manager 

Subscriptions Manager 

Outreach Manager 

Alex Dong 

Madison Houck 

Sophia Li 

Sophia Burick 

Anavi Uppal 

Hannah Han 

Kayla Yup 

Krishna Dasari 

Mia Gawith 

William Archacki 

Matthew Blair 

Jamie Seu 

Samantha Liu 

Anya Razmi 

Malia Kuo 

Madeleine Popofsky 

Sydney Scott 

Kara Tao 

Catherine Kwon 

Jenny Wong 

Lucas Loman 

Dinara Bolat 

Tori Sodeinde 

Georgio Maroun 

Yusuf Rasheed 

Alex Dong, Editor-in-Chief 

Madison Houck, Managing Editor 

About the Art 

Sophia Li, Managing Editor 

Rather than trying to visually 

represent all the science from the 

articles in this issue, I instead went 

with the overarching idea that 

scientists are always looking to reach 

new heights in their discoveries 

and innovations. Oftentimes, these 

attempts can fail, as symbolized by 

the falling ladders. However, the 

journey towards discovery persists, 

which I represented through the 

leaping figures. 

Catherine Kwon, Cover Artist 

OUTREACH 

Synapse Presidents 

Synapse Vice President 

Synapse Outreach Coordinators 

Synapse Events Coordinator 

WEB 

Web Managers 

Head of Social Media 

Social Media Coordinators 

STAFF 

Sanya Abbasey 

Luna Aguilar 

Ricardo Ahumada 

William Archacki 

Dinesh Bojja 

Risha Chakraborty 

Kelly Chen 

Leah Dayan 

Steven Dong 

Chris Esneault 

Erin Foley 

Mia Gawith 

Simona Hausleitner 

Tamasen Hayward 

Katherine He 

Miriam Huerta 

Sofia Jacobson 

Jenna Kim 

Catherine Kwon 

Charlotte Leakey 

Ximena Levya Peralta 

Yurou Liu 

Samantha Liu 

Helena Lyng-Olsen 

Kaley Mafong 

Georgio Maroun 

Cindy Mei 

Lee Ngatia Muita 

Lea Papa 

Hiren Parekh 

Himani Pattisam 

Emily Poag 

Madeleine Popofsky 

Tony Potchernikov 

Zara Ranglin 

Yusuf Rasheed 

Alex Roseman 

Ilora Roy 

Ignacio Ruiz-Sanchez 

Noora Said 

Hannah Barsouk 

Sofia Jacobson 

Jessica Le 

Kaley Mafong 

Lawrence Zhao 

Anjali Dhanekula 

Abigail Jolteus 

Emily Shang 

Elizabeth Watson 

Keya Bajaj 

Eunsoo Hyun 

Jamie Seu 

Kiera Suh 

Yamato Takabe 

Joey Tan 

Kara Tao 

Connie Tian 

Van Anh Tran 

Sheel Trivedi 

Robin Tsai 

Sherry Wang 

Elise Wilkins 

Aiden Wright 

Elizabeth Wu 

Nathan Wu 

Johnny Yue 

Iffat Zarif 

Hanwen Zhang 

Lawrence Zhao 

Celina Zhao 

Matthew Zoerb 

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

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

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

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

any submissions, solicited or unsolicited, for publication. This magazine is 

published by Yale College students, and Yale University is not responsible 

for its contents. Perspectives expressed by authors do not necessarily reflect 

the opinions of YSM. We retain the right to reprint contributions, both text 

and graphics, in future issues as well as a non-exclusive right to reproduce 

these in electronic form. The YSM welcomes comments and feedback. Letters 

to the editor should be under two hundred words and should include the 

author’s name and contact information. We reserve the right to edit letters 

before publication. Please send questions and comments to yalescientific@ 

yale.edu. Special thanks to the Yale Science and Engineering Association.

SPECIAL 

Timeline 

Timeline of Scientific 

ailures 

The scientific method—observation, analysis, and conclusion—optimistically presumes a cycle of discovery without errors. But on the lab 

bench, in the chemical hood, and under the lens of the most well-resolved microscope, any successful research project is also fraught with failure. 

This timeline aims to chronicle a brief history of scientific failures—to acknowledge the mistakes and missteps built into the process of scientific 

discovery, and thereby to better appreciate what it takes to discover the science that makes it into the pages of a textbook and scrawled onto a 

classroom blackboard. The pursuit of scientific knowledge is continuous and unrelenting—a test of patience and tenacity. We hope to demystify 

the process of scientific discovery by shedding light on the struggles it entails both for the novice and the seasoned researcher alike. 

4th Century BC 

Spontaneous Generation 

Aristotle formalized the theory of spontaneous generation, which 

stated that living organisms could be generated spontaneously out 

of nonliving matter. Common beliefs dictated that snails came 

from mud, scallops came from sand, and fleas came from dust. The 

theory wasn’t formally disproved until the 19th century. 

1828 

The Life—and Death—of Vitalism 

Vitalism was the theory that organic molecules 

could only be made by living systems that possessed 

a “vital force” integral to synthesis. In 1828, 

Frederick Woehler heated ammonium cyanate 

and produced urea, artificially synthesizing an 

organic molecule and discrediting the theory. 

1862 

A Guesstimation Gone Wrong 

Various Times 

All That Glitters Is Not Gold 

Lord Kelvin used thermodynamic 

calculations to estimate the age of the 

Earth and the Sun. His numbers—that 

Earth was somewhere between twentyfour 

million and four hundred million 

years old—were a gross underestimation. 

Today, we know Earth’s true age is about 

4.5 billion years. 

For centuries, alchemy attracted scores of scientists, 

including Isaac Newton, who hoped to transform 

base metals into gold and discover the elixir of life. Of 

course, these attempts were wholly unsuccessful. Still, 

they paved the way for chemistry as we know it today. 

BY KEYA BAJAJ | ART BY ANNLI ZHU 

Early 1700s 

The Theory That Burned Out 

In the 18th century, the existence of a 

fire-like element called phlogiston was 

posited. Advancements in chemistry 

revealed that it was flawed, and by the end 

of the century, the theory was abandoned. 

Phrenology was the widespread belief that 

the shape of one’s skull could be examined 

to determine personality traits. The theory 

proposed that the brain was composed of a 

variety of muscles with different functions 

that were smaller or larger depending 

on how frequently they were used. This 

practice of measuring the skull’s lumps to 

assess a person’s mental traits was largely 

disproven by the 1840s and was eventually 

dismissed as pseudoscience. 

1840s 

The Failure of Phrenology 

1887 

The Disappearing Act 

In the 19th century, it was believed that 

the medium for light waves was an unseen 

substance that filled the universe: aether. 

In 1887, Michelson and Morley performed 

an experiment to detect aether wind. They 

compared the speed of light in perpendicular 

directions to detect the relative motion of matter 

through “aether wind.” Unsurprisingly, light 

traveled at the same speed in both directions, 

leading to the dismissal of this theory. 


2022 

Theranos: From A Single Drop To A Huge Flop 

In November 2022, Elizabeth Holmes, former 

CEO of infamous health tech company 

Theranos, was sentenced to over eleven years 

in prison for defrauding Theranos investors. 

Valued at ten billion dollars at the heights of 

its hype, Theranos claimed to have developed 

a blood test that could use just a single drop 

of blood to rapidly and accurately diagnose 

an array of health conditions. However, it was 

revealed shortly thereafter that Theranos had 

never in fact developed a functional blood test 

device, resulting in Holmes’ eventual arrest. 

1962 

Reversing Cellular Irreversibility 

1928 

The Serendipity of Penicillin 

In 1928, Dr. Alexander Fleming noticed mold 

growing on his Petri dish on staphylococcus 

bacteria. Something seemed to prevent the 

surrounding bacteria from growing—which 

we now know to be penicillin. This accidental 

discovery paved the way for the rise of 

antibiotics and their therapeutic benefits. 

1912-1953 

The Paleontological Prank 


Until the late 19th century, it was widely 

believed that cell differentiation was 

irreversible: a cell, once specialized, 

could not return to its original stem cell 

state. In 1962, John Gurgeon, among 

others, proved this wrong by defining 

the cell reprogramming technique, 

cloning frogs using nuclear transfer 

from differentiated cells, thus reversing 

differentiation. 

In 1911 and 1912, fossils discovered in 

Piltdown, England were believed to be 

those of the Piltdown Man, the missing link 

between apes and humans and the “earliest 

Englishman.” However, by 1953, it was 

discovered that the fossils were nothing but an 

elaborate forgery, involving a modern human 

skull and orangutan jawbone. 

In November 2017, the first annual Flat Earth 

International conference was held in Raleigh, 

North Carolina. Contrary to popular belief, the 

“scientific” theory that the Earth was flat rather 

than a sphere was most popular in the late 19th 

and early 20th century. Despite overwhelming 

(and obvious) evidence of Earth's spherical nature, 

a small, yet vocal, contingent of people continue to 

promote the theory of a flat Earth. 

In 1953, Watson and Crick famously 

announced their discovery of DNA’s double 

helix. Just earlier that year, though, chemist 

Linus Pauling, a two-time Nobel Prize 

winner, proposed that DNA comprised 

three intertwined strands, which we know 

today to be false. In stark contrast with the 

success of his model for protein structure, 

his DNA model was incorrectly built insideout, 

with three strands instead of two. 

Timeline 

SPECIAL 

2017 

Flat Earth Fanatics 

1998 

A Vexing Claim About Vaccines 

In 1998, Andrew Wakefield of the Royal Free 

Hospital School of Medicine published a study 

in The Lancet claiming that the measles, mumps, 

and rubella vaccine caused autism. The medical 

community quickly condemned the research 

study as clearly flawed in its design, and it was 

eventually retracted and declared fraudulent in 

2011. However, Wakefield remains a popular 

figure among the growing anti-vax movement. 

1953 

Pauling’s Triple Trouble 

1918-1926 

YSM’s “Troubled Years” 

The Yale Scientific Monthly, founded in 1894, was 

the predecessor to the Yale Scientific Magazine. 

While it took off in its early years, it faced its 

biggest hurdle in its 19th volume. The editorial 

board of the Monthly began focusing on student 

affairs at Yale’s Sheffield Scientific School. This 

choice diluted scientific content, until 1926, when the magazine was 

revived in its original vision as the Yale Scientific Magazine, which 

launched in 1927. The period from 1918 to 1926 has been dubbed by 

YSM’s Wikipedia page as “The Troubled Years.” 


& 

By Sunny Vuong 

WHY IS “DISRUPTIVE” SCIENCE 

DWINDLING, WHILE “HYPE” 

LANGUAGE IS ON THE RISE? 

Find yourself wondering where the hype is? Look no further 

than recent language trends in science. Researchers in Japan 

and Canada examined 901,717 successful grant application 

abstracts submitted to the National Institutes of Health and found 

a significant increase in the use of promotional language from 1985 

to 2020. The 2022 study, published in the Journal of the American 

Medical Association, identified 139 adjective forms associated with 

hype, such as “novel,” “critical,” and “key,” with 130 of these showing 

an increase in frequency by 1,378 percent. 

In a separate trend, researchers from the Universities of Minnesota 

and Arizona explored whether scientific innovation is becoming 

more or less disruptive. They created the CD index, which measures 

disruptiveness by examining whether subsequent works cite the study 

itself (an indicator of greater disruptiveness) or the study’s references. 

The findings, published by Nature in January 2023, revealed 

that papers published since 1945 are less likely to be disruptive 

and more likely to consolidate existing knowledge. While older 

manuscripts from the 1950s tended to use words evoking discovery 

(such as “produce” or “determine”), recent research favored words 

referring to incremental progress (such as “improve” or “enhance”). 

Researchers concluded that a balance between disruptive research, 

which pushes boundaries, and incremental research, which refines 

existing knowledge, is essential to scientific advancement. 

Although these phenomena are revealing about modern scientific 

trends, it’s still unclear what the reasoning is behind them. Hype 

language and disruptiveness in science have yet to be declared as 

inherently good or bad—that may be for scientists now exploring 

these tendencies to decide. ■ 

AMMONIUM CHLORIDE: 

FERTILIZER INGREDIENT, 

PICKLING AGENT... 

OR THE SIXTH TASTE? 

By Ethan Powell 

Sweet, sour, salty, and bitter were long believed to be the four 

basic human tastes. In the early twentieth century, a Japanese 

scientist claimed that the savory taste found in soy sauce was 

unique, and by 2002, "umami" was accepted as the fifth basic taste. 

Now, the discovery of a potential sixth taste—ammonium chloride— 

has brought scientists at the University of Southern California to the 

forefront of gastronomic research. 

Detectable in Scandinavian licorice, ammonium chloride has an 

enigmatic quality that recalls the sharpness of sea air or an earthy 

brininess. The compound, found in batteries and fertilizers, changes 

our perception of taste by modulating the flow of hydrogen ions, 

or protons, through OTOP1 receptors—protein channels in our 

taste bud cells associated with the detection of sourness. When 

dissolved in water, some ammonium molecules lose a hydrogen ion 

to form ammonia, which diffuses into our taste bud cells and lowers 

the intracellular proton concentration. The difference in proton 

concentration across the cell membrane drives their movement 

through the OTOP1 receptors, affecting our perception of taste. 

Researchers speculate that ammonium chloride’s distinctive flavor 

provided an evolutionary signal that steered ancient humans away 

from harmful substances. In experiments involving human cell 

cultures and live mice, researchers observed that mice with an intact 

OTOP1 receptor showed avoidance behaviors when introduced to 

ammonium chloride, while those without OTOP1 did not exhibit 

any reaction. 

As gastronomes and scientists alike await further studies, this 

research paves the way for not only a new category of taste but also 

a deeper understanding of the origins behind our dietary choices. ■ 


Profile 

SHORT 

BRIAN NOSEK, GRD ‘02 

A CRISIS OF RESEARCH REPRODUCIBILITY 

BY NATHAN WU 

Replication is a key tenet of the scientific method. In theory, any 

discovery should be reproducible with identical procedures. 

However, scientists have become increasingly aware that 

in practice, most studies’ findings may be irreplicable, hinting at 

systemic flaws deep within scholarly research. 

After all, how can science be trusted if it 

builds upon unrepeatable results? 

Few understand these flaws better than 

Brian Nosek (GRD ‘02), co-founder and 

director of the Center for Open Science 

(COS). In 2015, Nosek and the COS 

made waves when they published a 

study in Science in which less than 

half of their attempts to replicate 

one hundred psychology 

experiments were successful. 

The study was among the first 

to empirically characterize the 

extent of the reproducibility crisis, 

drawing attention from scientists 

and non-scientists alike. 

Nosek traces his interest in 

interrogating the scientific process to a 

research methods class taken during his 

PhD at Yale. Nosek recalls reading papers 

detailing common issues in scientific practice, 

from publication bias to ignoring null results, and 

their solutions. What shocked him was that these studies dated back 

to the ‘60s. “We’re reading these papers in the 1990s, and for me, it 

was like, ‘wait a second—we’ve known the problem, we’ve known the 

solution; thirty years later, we’ve done nothing… what’s going on?’” 

Nosek said. 

This lack of progress led Nosek to take an interest in improving 

his own research methodology. One year, he collected data at the 

beach to obtain larger sample sizes. The next, he created a website 

to collect data on implicit biases, long before online data collection 

was commonplace. This would grow to become Project Implicit— 

since its creation, over twenty million people have taken an implicit 

association test on the site. 

When Nosek became a professor at the University of Virginia, 

his focus shifted beyond improving just his own methodology. “We 

started thinking about how we could build tools to help others do 

the same,” Nosek said. However, this technology-building work 

was ineligible for most grants, limiting its scope. All this changed 

in 2013 when Nosek received five million dollars from the Arnold 

Foundation to scale up his operations, thus creating the COS. 

The COS was originally centered around two projects from Nosek’s 

lab: the psychology “reproducibility project” and the creation of 


Image Courtesy of the Center for Open Science 

the Open Science Framework (OSF). The OSF is a tool to help 

researchers document and share their experimental progress, all 

while promoting open science practice: making the entire research 

process transparent. Unlike the traditional system of only publishing 

completed work, the OSF tracks a project’s whole journey, 

including the initial research plan, any changes to it, 

null results, and more. 

The COS has grown substantially since its 

creation. In 2020, it introduced the Transparency 

and Openness (TOP) Factor, a metric to 

evaluate research journals’ adoption of the 

best practices of open science. 

In 2021, it released the results of a 

replication project focusing on cancer 

biology research. Open science has 

been growing, too. “If you look at 

every key performance indicator, 

the growth over the last decade 

has been nonlinear,” Nosek said. The 

OSF now has over half a million users, 

and many others have conducted studies 

evaluating replicability in fields from ecology 

to economics. 

Nosek hopes to add tools to the COS to help 

not only those producing research, but also 

those utilizing it. “What we want to do in the next ten 

years is [add] in the interaction between the research 

producer and the research consumer,” Nosek said. “The consumer 

could be policymakers or people way outside of the process.” 

Facilitating dialogue between research producers and consumers 

could hold researchers accountable for the thoroughness of their 

experimentation and reporting. 

So, how do we fix the reproducibility crisis? 

Nosek believes that changes to the publication process are 

required. Under the current model, scientists are rewarded for 

producing publishable findings. His proposed alternative is the 

“Registered Reports” model, where peer review is conducted prior 

to data collection, shifting the focus from getting results to having 

watertight methods. “Registered Reports changes the reward system 

for researchers… the decisions at journal level are no longer about 

the outcomes—they’re about the questions,” Nosek said. 

Despite his familiarity with the challenges of the knowledge 

production process, Nosek’s belief in science is unwavering. “The 

reason to trust science is because science doesn’t trust itself,” Nosek 

said. While mistakes are inevitable when pushing the boundaries 

of knowledge, what matters is that science is open for revision. For 

all the flaws plaguing the research process, science’s self-correcting 

nature remains ever-present. ■ 


Profile 

SHORT 

MARC ABRAHAMS 

MISSION IMPROBABLE 

BY MIA GAWITH 

Have you ever 

wondered about 

the physics behind 

why our cereal becomes 

soggy in milk, the most 

efficient way to turn a 

doorknob, an advanced 

toilet that analyzes what 

we excrete, or a method of 

identifying narcissists by 

looking at their eyebrows? 

The ideas may seem 

silly—improbable, even— 

but this is exactly the 

type of research that Marc 

Abrahams celebrates. 

After graduating in applied 

mathematics from Harvard 

University, Abrahams spent 

the early years of his career running a software company and writing 

humorous, inquisitive articles about science. But one day, a question 

struck him: Were there any journals that would publish the type of 

bemusing—yet very real—topics he wrote about? 

In 1995, Abrahams took matters into his own hands and cofounded 

a magazine that did just that: the Annals of Improbable 

Research (AIR). AIR’s website reads: “Real research, about anything 

and everything, from everywhere—research that’s maybe good or 

bad, important or trivial, valuable or worthless.” Four years earlier, 

Abrahams had also founded the Ig Nobel Prize Ceremony—an honor 

bestowed to researchers of both the unusual and the imaginative. 

Every year, traditional Nobel Laureates award Ig Nobel Prizes 

to the winners in a grand ceremony, which took place at Harvard 

University before the COVID-19 pandemic. Thousands of award 

nominations come in every year, but only a select few are chosen. 

1,100 spectators crowd into a room as paper airplanes fly in a 

dizzying flock above their heads and mini opera songs are bellowed 

across the stage. And looming above it all is the official mascot, 

“The Stinker”—a rendition of Auguste Rodin’s The Thinker statue 

fallen onto its back with its buttocks in the air. 

If that mental image made you pause and chuckle (internally 

or externally), then the ceremony did exactly what it intended. 

Abrahams’ work injects fun into science—the AIR and the Ig Nobel 

Prizes are united by an important goal: “to honor achievements 

that make people LAUGH, then THINK.” 

Abrahams argues that research is a process of discovery, one 

that ascribes importance to topics over time. Sometimes, the 

most important scientific advancements can be overshadowed 

for many years, their importance not discovered until much later. 

“Sometimes it’s years, sometimes it’s decades, and sometimes it’s 

centuries before people realize you can use [a discovery] to do 

something, and it changes everything,” Abrahams said. “The fact 

that something doesn’t seem important doesn’t really mean it’s not.” 

As such, Abrahams brings attention to research that is often 

overlooked in the scientific community, and which the public may 

otherwise never learn about. From this perspective, humor acts 

as the driving force behind the success of the AIR and Ig Nobel 

Prizes. On the one hand, humor can draw in both scientists and 

non-scientists alike. It’s one thing to sit in a crowded auditorium 

and watch researchers be solemnly awarded prizes; it’s another 

thing to watch the same researchers present their research in an 

exciting, often quick-witted way. 

At the same time, people may begin to pause and contemplate 

scientific research in ways they never had before. If you heard 

about a group of scientists who invented a toilet that analyzes 

excrement, you might be slightly grossed out at first, but you 

might also start to wonder: What technologies did they develop? 

Does this have applications for public health? Can we utilize the 

technology somewhere else? 

“This is a way of bringing a lot of stuff to people’s attention—stuff 

they would probably try to normally stay away from,” Abrahams 

said. “But now it’s the thing they want to know about most.” 

Abrahams is known by many monikers: “the Puck of Science” by 

the Journal of the American Medical Association and “the nation’s 

guru of academic grunge” by The Washington Post, to name a few. 

But talking to him, while he cracks jokes with a blown-up banner 

of “The Stinker” behind him, reveals who he is at heart: a scientist, 

guided by humor, with a profound drive to revitalize science. ■ 

PHOTOS COURTESY OF MARC ABRAHAMS 


Profile 

SHORT 

STUART FIRESTEIN 

FASCINATION WITH FAILURE 

Stuart Firestein, the former chair of Columbia 

University’s Department of Biological 

Sciences, is a neuroscientist who studies 

the olfactory system, but he’s also an expert 

in something else—failure. In 2015, Firestein 

released a book, titled Failure: Why Science Is 

So Successful, that places failure at the heart 

of the scientific process. 

Firestein’s journey toward the topic of failure 

began while he was teaching a large cellular 

and molecular neurobiology lecture course 

at Columbia. For many years, his students 

were expected to read an excessively long 

textbook, titled Principles of Neuroscience. 

“It’s a book about the brain that weighs twice 

as much as the brain,” Firestein said. 

Firestein noticed a critical gap between 

what students were learning in the classroom 

and what the researchers were doing in the 

lab. “[Students] must have thought that the 

process of science is to get a lot of facts, put 

them in these books, and force [students] to 

memorize them and spit them back up on an 

exam, which is a very unpleasant experience,” 

he said. “And that’s not true either. [Scientists] don’t accumulate 

facts —we accumulate questions.” 

The experience led him to create a new course called “Ignorance,” 

which consisted of a variety of science faculty members meeting 

with students once a week for two hours to talk about everything 

they don’t know. “What’s their question?” Firestein asked. “Why 

did they settle on that as the important question? What are the 

other questions they’re ignoring while looking at this one? What 

are the questions this question will lead to?” 

The course became very popular as students began to 

understand scientific research not as a quest for facts, but rather 

as an investigation of ignorance. This course not only inspired 

Firestein’s first book, Ignorance: How It Drives Science, but also 

served as a jumping-off place for his contemplation of the role 

of failure in science. 

According to Firestein, failure is the best way to identify 

the questions that lay at the root of our scientific ignorance. 

“Let’s say you do an experiment, and it fails,” Firestein said. 

“There must be something you didn’t know when you set this 

up. We have to do some experiments before this experiment to 

figure out what it is we’re missing.” In Firestein’s view, failure 

IMAGE COURTESY OF STUART FIRESTEIN 

BY KAVYA GUPTA 

is an essential part of the scientific 

process that reveals our ignorance 

in actionable ways. Failure points 

the finger at what we don’t know, 

which allows us to then turn around 

and ask more meaningful questions 

about science. “It’s a way of gaining 

knowledge in the same way as a 

successful experiment. It is no less 

valuable, no less important, and no 

less a part of the process,” Firestein 

said. “So, things should fail. In fact, 

I think they should fail at a fairly 

high rate.” 

Despite its importance to scientific 

discovery, many students still struggle 

greatly with embracing failure. “We 

tend not to accept failure easily,” 

Firestein said. “We tend to see it as a 

negative.” He looks at natural failures 

in our environment to justify why we 

should be more open to failing. 

“If you look at the top predators, like 

lions and tigers, I think most of us think 

that they can just go out anytime they get a little hungry and 

bag a snack somewhere,” Firestein said. “But that’s not actually 

true. When you look at the predator-prey literature, you find 

these big critters are successful fewer than twenty-five percent 

of the time they go after something. Seventy-five percent of 

the time, the critter escapes.” Even the top of the top encounter 

failures, yet they learn from them and continue to try, whether 

by changing their methods or trying a new approach. 

Similarly, Firestein argues that accepting the natural likelihood 

of failures is especially important. “It is a regular part of the 

process,” he said. “It’s not like success and failure are two sides 

of a coin, but rather like two horses pulling a wagon in the same 

direction in their own particular way.” 

This is sometimes hard to understand, especially for young 

scientists who have struggled with accepting their failures in the 

past, but it’s a key part of finding the most fascinating scientific 

questions. “The truth, the correct answer, is narrow,” Firestein 

said. “It’s just narrow, and it doesn’t go anywhere. Whereas 

there are endless ways to screw up, and many of them are quite 

interesting. They take you down new pathways. Quite often, the 

screw-ups are really where the data comes out.” ■ 



FOCUS 

Cosmology 

REDISCOVERING 

COSMIC ORIGINS 

THE BIRTH OF THE SOLAR SYSTEM 

BY DAVID GAETANO | ART BY ANNLI ZHU 

It is easy to take for granted the vast scope 

of scientific understanding that humans 

have acquired over hundreds of thousands 

of years on Earth. Today, for example, the 

origin of the solar system is relatively well 

understood. But not too long ago, we were 

searching for an answer among a sea of 

endless theories. 

An article from the 1941 edition of the 

Yale Scientific Magazine (Vol. 15 No. 4), titled 

“The Origin of the Solar System,” is a time 

capsule that provides a firsthand account of 

the scientific community’s understanding 

of the solar system’s origins at the time. The 

writer, Lyman Spitzer Jr., was a well-respected 

Yale faculty member who earned his PhD 

in physics from Princeton University in 

1939. In his piece, Spitzer sought to analyze 

contemporary understanding of the origin 

of the solar system and place doubt on the 

existing theories of the time. 

Eighty years later, this article revisits 

Spitzer’s analysis. By reflecting on evolving 

scientific understanding, we can help 

provide motivation for further scientific 

advancement, as the cosmos still leaves much 

to be discovered. 

Early Theories 

“The rise and subsequent decline of the 

most important theories of the origin of the 

solar system are an instructive chapter in 

the history of science and cast light on the 

problems which an ultimately successful 

theory must face,” Spitzer wrote. At the time 

of his article, there were many different 

hypotheses surrounding the formation of 

the solar system, yet none could truly be 

rigorously proven. In fact, Spitzer criticized 

two of the leading hypotheses for their lack of 

concrete evidence. 

The first theory he analyzed was the 

nebular hypothesis, which argued that the 

sun was first created out of a huge, rotating 

cloud of gas and dust in space, which was 

then flattened into a disk. This disk would 

have subsequently condensed to form the sun 

and various planets seen in the solar system 

today. He argued that this hypothesis was 

impossible due to the conservation of angular 

momentum, which means that the sun would 


Cosmology 

FOCUS 

have to rotate much faster than observed to 

maintain the known laws of the universe. 

The second hypothesis Spitzer examined 

was coined the encounter theory. This idea 

proposed that the solar system was formed 

from the collision of two stars. This would 

give rise to the planar nature of the observed 

solar system as well as the debris and planets 

that orbit around the sun. However, Spitzer 

was not a fan of this hypothesis either. He 

argued that the debris pulled from the nearcollision 

of two stars would not have been 

able to condense into planetary objects like 

the ones observed today in the solar system. 

Such rapid cooling of the nebular gasses 

would have manifested into something more 

akin to an explosion rather than spherical 

planets, according to his theoretical 

calculations. “The origin of the solar system 

may well be a riddle which science will never 

wholly solve,” he concluded. 

Advancements in Scientific Technology 

The foundation of scientific study is 

rooted in empirical evidence and a rigorous 

commitment to skepticism. Spitzer’s article 

did not seek to reject ideation, but rather to 

adhere to the scientific method’s demands 

that theories be substantiated with empirical 

data. “There's nothing wrong with having an 

idea of how something might work without 

being able to go out and measure it,” said 

Charles Bennett, a professor of physics and 

astronomy at Johns Hopkins University. “In 

the end, you need to match simulations with 

observations to know that what you're doing 

is right.” 

Spitzer’s critiques shed light on the 

technological limitations of his time, which 

prevented many scientists from being able 

to experimentally prove their conclusions. 

Spitzer acknowledged that the mathematics 

required to go back two billion years is an 

“ambitious calculation” that would probably 

never be attempted. 

Today, the scientific landscape has evolved 

significantly. Technological advancements, 

particularly in computing technology and 

simulation power, have revolutionized 

our ability to create intricate models of the 

formation of the solar system. Further, the 

Hubble Space Telescope has even been used 


to photograph stars surrounded by accretion 

disks of gas and dust, signaling an early stage 

of planetary formation. These new findings 

have proven pivotal: while Spitzer discounted 

the nebular hypothesis in his article, now we 

know it was not far off. 

The Winning Hypothesis 

Since Spitzer’s time, scientists have been 

able to conclude that the solar system was 

very likely created through the collapse 

of a nebular cloud of gas and dust from 

a nearby supernova. Today, the “solar 

nebula hypothesis” is widely accepted to 

be the most accurate account of the solar 

system’s origins. 

Avi Loeb, a renowned theoretical physicist 

and professor at Harvard, described the 

formation of the solar system as a series of 

events caused by a nearby supernova event, 

which is a massive explosion of a star that 

releases immense amounts of energy and 

material into space. The solar system formed 

about 4.6 billion years ago—just about onethird 

of the existence of the universe—from a 

giant cloud of gas and dust. The shockwaves 

from the supernova then triggered the 

collapse of this cloud. As it collapsed, gravity 

pulled the material together at the center, 

forming the sun, which is mostly composed 

of helium and hydrogen. 

Over time, small particles of leftover 

mass in the form of dust and gas began 

to condense in orbit around the early sun. 

This then created the rocky planets closest 

to the sun—where the hydrogen would 

be absorbed more quickly—leaving the 

gaseous planets like Jupiter and Neptune 

further away in orbit. “The universe started 

from a pretty uniform distribution of 

matter. There were small differences in the 

density of matter, and they grew over time 

because of gravity,” Loeb said. This process 

led to the diverse and fascinating solar 

system we know today. 

ABOUT THE AUTHOR 

One article, written by Michael Perryman 

of the University of Bristol, explained that this 

current “solar nebula hypothesis” accounts 

for early issues with the nebular hypothesis, 

such as the angular momentum discrepancy 

that Spitzer highlighted. Somehow the sun 

maintained most of the mass, but only a tiny 

percentage of the angular momentum of 

the solar system. The new theory reconciled 

this discrepancy by more chronologically 

describing the process by which the nebula 

compressed into a disk before beginning the 

sequential process of planetary formation. 

A Glimpse Forward: Finding Life 

Although the mystery of the origin of the 

solar system is somewhat resolved, there 

are natural questions that these resolutions 

leave unanswered. One such question is the 

existence of extraterrestrial life. By studying 

the formation of our solar system and the 

emergence of life on Earth, scientists can gain 

valuable insights into the potential habitability 

of other planets and celestial bodies. “Looking 

for life around stars is a very exciting frontier,” 

Loeb said. “One can search for signatures of 

microbial life. But one can also search for 

intelligent life.” 

Loeb highlighted the notion that the laws of 

physics, chemistry, and biology are universal, 

suggesting that the conditions conducive 

to life on Earth may very possibly exist 

elsewhere in the cosmos. This perspective 

enables scientists to assess the likelihood of 

life on exoplanets. 

Spitzer, eighty years ago, was simply 

hoping to figure out how the solar system 

formed. Now that we know the conditions 

that led to life within our solar system, we 

can launch a new quest for life beyond our 

planet. We have the means to explore the 

broader cosmic environment and likewise 

form new hypotheses, critiques, technologies, 

and conclusions in the ongoing pursuit of 

alternative forms of life. ■ 

DAVID GAETANO 

DAVID GAETANO is a sophomore in Ezra Stiles College studying mechanical engineering. In addition to 

writing for YSM, he is involved in the rocketry subteam of the Yale Undergraduate Aerospace Association. 

THE AUTHOR WOULD LIKE TO THANK Avi Loeb and Charles Bennett for their time and enthusiasm 

for scientific advancement in cosmology. 

FURTHER READING: 

Loeb, A. (2023). Interstellar: The Search for Extraterrestrial Life and Our Future in the Stars. Mariner Books, 

an Imprint of HarperCollins Publishers. 


FOCUS 

Medicine 

NATURE 

VS NURTURE 

Is Alcohol Use Disorder in Our Genes? 

By Matthew Blair and Lea Papa 

It is no secret that the genes we inherit from 

our parents determine simple physical 

traits such as hair color and height. That 

comes down to a mixture of certain genes, 

which include a randomness component 

related to the allele—or gene variant—we 

inherit. But when it comes to more complex 

human features, the connection to our genes 

is less clear. The impact of genes on behavior 

like alcohol use or even sexual orientation has 

long been the subject of scientific debate. 

In an article published in the Yale Scientific 

Magazine in 1929 (Vol. 3 No. 2), Yale Professor 

R. P. Angier weighed in on this “nature vs. 

nurture” debate. He questioned if our traits 

are impacted not only by complex genetic 

combinations, but also by the environment 

in which we live. He discussed two major 

schools of thought: the instinctivists and the 

environmentalists. The former hold the belief 

that our instinct, which we inherit and thus 

have no control over, drives our actions. The 

environmentalists differ. They believe that 

only the most basic of actions—like knowing 

how to swallow or turn one’s head—are 

inherited, while all other actions are learned 

through a process of trial and error. Angier 

himself took a binary approach to this debate, 

concluding that traits fall into one category or 

the other. “Alcoholism used to be labeled as 

a hereditary trait,” he wrote, “No competent 

medical man thinks so nowadays.” 

Since then, the current understanding 

of genetics and environmental factors has 

combined these two schools of thought, with 

alcohol misuse serving as an interesting test 

case. Both genetics and our environment play 

a role. “One is not against the other, but rather 

they both contribute to the predisposition 

to psychiatric and behavioral traits,” said 

Renato Polimanti, an associate professor of 

psychiatry at the Yale School of Medicine. So, 

how did we come to prove Angier wrong? 

The Unique Case of Alcohol Use Disorder 

Alcohol use disorder (AUD) is a leading 

cause of death and disability worldwide and 

is characterized by frequent and problematic 

drinking behaviors, such as binge drinking, 

loss of control, and continued drinking 

despite harmful consequences. In the 170 

years since the term “alcoholism” was first 

classified as a behavior, problematic drinking 

has been a widely studied condition to settle 

the nature versus nurture argument. 

Early on, it was believed that alcoholism was 

inherited. This simple view, however, quickly 

started to change. By 1929, as Angier wrote, 

the general view had completely reversed: 

alcoholism was primarily seen as the result 

of environmental factors. When AUD was 

classified as a brain disorder in 1956, as we 

generally understand it today, this issue took 

a far more complicated turn. 

As it turns out, there is no “alcoholic” gene 

in the human genome, nor is there an absolute 

“AUD-causing” environment or situation. 

Art By Patricia Joseph 


Medicine 

FOCUS 

Alcoholism 

has a substantial 

impact on both mental and 

physical health and can present different 

features among affected individuals. Due to 

this, the mechanisms and possible causes of 

alcoholism cannot be as easily identified as 

diseases such as hemophilia, which presents 

clear physical symptoms. But in the decades 

since Angier’s article, scientists have made 

strides in figuring out the mystery of what 

really underlies this unique disease. 

Searching for AUD in Our Genes 

In 1990, an initially promising study of the 

genetic basis of alcoholism was conducted by 

Kenneth Blum, a professor at the University 

of Texas Health Science Center. The study 

found that there was a very strong connection 

between the D2 dopamine receptor gene and 

the development of alcoholism or problematic 

drinking behaviors. In their patient sample, 

the researchers found that in those with AUD, 

all had a higher frequency of one specific allele 

in the dopamine D2 receptor gene, suggesting 

that it was strongly associated with AUD. 

However, one year later, Joel Gelernter, a 

professor of genetics and neuroscience at the 

Yale School of Medicine, along with his team 

could not find the association between the D2 

dopamine receptor gene and AUD, showing a 

lack of replicability in the earlier study. 

While the D2 dopamine receptor gene did 

not have the effect expected on alcoholism, 

the study contributed to moving forward 

genetic research. “We know now that it was 

only a first step of a very long road of complex 

genetics,” said Renato Polimanti, a colleague 

of Gelernter at the Yale School of Medicine. 

In contrast to Angier’s conclusion that AUD 

is decided by the environment, scientists have 

since found multiple genetic players. 

The effort to uncover the genetic mysteries of 

AUD was—and is—long from over. Between 

the D2 dopamine receptor findings in the 

1990s and 2020, researchers have identified 

more than a dozen variants for AUD. In 2020, a 

research team including Gelernter, Polimanti, 

and Hang Zhou, an assistant professor of 

psychiatry at Yale, was able to greatly expand 

upon previous findings regarding alcoholism 

through a genome-wide association study 

published in Nature Neuroscience. 


The team was able to identify twenty-nine 

genes linked to increased risk of problematic 

alcohol use—nineteen of them novel—in the 

human genome, extending the known genetic 

architecture of the disorder and giving other 

scientists a wider breadth of targets for followup 

studies. Researchers found that six to 

eleven percent of the phenotypic variation— 

referring to differences in what physical and 

behavioral traits are expressed—could be 

explained by genetic information. 

The goal of genetic studies, however, is 

not only to find associations but also to 

understand how these variants might promote 

the development of AUD. In their study, 

the Yale team discovered that the risk genes 

were correlated to changes in certain brain 

regions. This finding suggested to researchers 

that the risk variants promoted certain brain 

pathways that contribute to the development 

of behavior patterns and disorders. 

Such pathways are not exclusive to AUD. 

The researchers discovered a strong genetic 

correlation between problematic alcohol 

use and 138 other conditions, including 

substance abuse disorders, depression, and 

schizophrenia. “AUD has many variants 

across the genome that are involved in the 

predisposition of this trait, but these variants 

are not only predisposing to AUD, they are 

predisposing to many things,” Polimanti 

said. “It can depend on where [risk variants] 

play a role, maybe in sensitivity to a 

substance, or to addiction pathways in the 

brain, or to reward systems.” 

Moving Forward 

This research does not mean AUD is solely 

explained by genetics. Rather, in AUD, only 

about fifty percent of the risk appears to be 

attributed to our genes. This is relatively 

ABOUT THE 

AUTHORS 

small in comparison to schizophrenia, 

where genetics can explain eighty percent 

of the disease predisposition. Therefore, as 

research progresses, consideration must 

still be made for the environment—the 

“nurture”—that individuals were raised and 

live in. “Genetic variants among individuals 

cannot explain everything. We need to 

spend more time in gene discovery before 

bringing it into patient care,” Zhou said. 

Beyond addressing the nature versus 

nurture debate, this research has a broader 

aim. According to Polimanti and Zhou, 

geneticists hope to be able to bring their 

findings to human healthcare in order to 

help predict and treat certain illnesses. This is 

called precision medicine, wherein a person’s 

treatment plan can be specially tailored based 

on their unique genetic makeup. 

Until we get there, research will continue 

focusing on identifying genetic variants and 

possible mechanisms behind risk. Polimanti 

explained that for certain illnesses like 

cardiovascular disease, the field of genetics 

is expected to transform treatments in the 

coming years. “We will keep doing gene 

discovery and use increasingly advanced 

technology to deliver this information and get 

a deeper understanding of the role genetics 

play in human health,” Zhou said. 

The study of AUD has been marked 

by both successes and failures. Now, we 

enter an exciting time where genetic and 

environmental studies promise great strides 

for the understanding of our human genome 

and real changes in clinical care. Nature and 

nurture, instinctivists and environmentalists, 

the D2 dopamine receptor and twenty-nine 

other discovered genes, and, now, precision 

medicine, are all important themes in the 

long and evolving story of alcoholism and 

scientific discovery. ■ 

MATTHEW BLAIR 

LEA PAPA 

MATTHEW BLAIR is a sophomore in Benjamin Franklin College from Manchester, NH, majoring in 

the History of Science, Medicine, and Public Health. In addition to copy editing for YSM, Matthew 

conducts lung cancer research in the Schalper Lab at the Yale School of Medicine and plays for the 

club ice hockey team. 

LEA PAPA is a sophomore in Ezra Stiles College from South Milwaukee, WI, studying neuroscience. 

Outside of YSM, Lea is involved in Yale’s Questbridge Chapter, is working towards becoming an EMT, 

and recently joined the Yale Undergraduate Research Journal Humanities Committee. 

THE AUTHORS WOULD LIKE TO THANK Renato Polimanti and Hang Zhou for their time and expertise. 


FOCUS 

Infectious Disease 

THE 

TO FIGHT TICKS 

TICKING CLOCK 

THE LYME DISEASE VACCINE'S 

COMEBACK STORY 

BY CINDY MEI 

ART BY DIYA NAIK 



FOCUS 

Tick spray might not be the first thing 

you think of when preparing to 

go backpacking. However, if gone 

undetected, these small arachnids can 

feed and feed, increasing the likelihood 

of transmission of dangerous bacteria. 

Named for the city of Lyme, Connecticut, 

where it was first detected, Lyme disease is 

most commonly spread by Ixodes ticks and 

is the most common tick-borne illness in 

the Northeast region of the United States. 

If left untreated, the disease can cause 

debilitating effects on the heart, joints, 

muscles, and nervous system. According 

to the CDC, reports of Lyme disease have 

doubled in the United States since 2000, 

reflecting a growing need for prevention. 

In 1993, the Yale Scientific Magazine 

reported on a novel vaccine being tested 

against Lyme disease (Vol. 67 No. 2). The 

writer, Emily Ho, estimated that the vaccine 

would be “available for the public sometime 

in 1995.” However, as of today, there are 

no Lyme disease vaccines available for 

humans. What went wrong? 

Revisiting the Past 

The story began in 1988, when Erol 

Fikrig—then a postdoctoral researcher— 

met with Richard Flavell, who was the 

newly appointed chair of immunobiology at 

the Yale School of Medicine. “We decided, 

why don’t we make a vaccine against Lyme 

disease?” said Fikrig, now the Waldemar 

von Zedtwitz Professor of Medicine at Yale. 

So, they started looking for a target. 

Lyme disease is caused by Borrelia 

burgdorferi, which is a pathogenic spirochete 

(a type of slender, spiral-shaped bacteria). 

It was known that a key part of protection 

against Lyme disease in animals is mediated 

by humoral immunity, a type of immune 

response that can be passive or active. In 

active immunity, B cells (a type of white blood 

cell) produce antibodies that specifically 

recognize and destroy an encountered 

foreign antigen, conferring future protection 

against that antigen. In passive immunity, 

blood serum containing these antibodies 

can be transferred to other animals to confer 

protection against the target antigen. 

Previously, it was shown that 

immunization of hamsters with serumcontaining 

antibodies against B. burgdorferi 

prevented infection when the hamsters 

were challenged with the bacterial strain. 

Dr. Erol Fikrig pipetting in the lab. 

PHOTOGRAPHY BY PAUL-ALEXANDER LEJAS 

However, scientists did not know what 

specific antigens trigger the production 

of protective antibodies against Lyme 

disease. Fikrig and Flavell would have to 

solve that mystery. 

In their 1990 paper published in 

Science, Fikrig and Flavell—along with 

collaborators Stephen Barthold and Fred 

Kantor—hypothesized that a possible 

candidate for the antigen was outer surface 

protein A (OspA), which is a lipoprotein (a 

particle composed of fats and proteins), on 

B. burgdorferi. To test this hypothesis, the 

gene for OspA in a B. burgdorferi strain 

was cloned into the bacteria E. coli, such 

that the E. coli would express OspA. Mice 

then received either the OspA-transformed 

bacteria or a control. Four weeks later, an 

antibody response was detected in mice that 

received the OspA-transformed bacteria, 

suggesting that humoral immunity had 

developed in response to OspA. 

The team found that the mice that received 

the OspA-transformed bacteria were 

successfully protected from infection from B. 

burgdorferi. While the control mice showed 

evidence of arthritis, inflamed heart tissue, 

and infection in blood and spleen cultures, 

mice that received the OspA-transformed 

bacteria showed no sign of infection—all 

signs pointed towards successful immunity. 

Lastly, the researchers found that the serum 

of the protected mice conferred similar 

prevention against infection when injected 

into new mice, demonstrating effective 

passive immunization. 

Studies like this one paved the way for a 

human vaccine against Lyme disease. Indeed, 

in the YSM article published thirty years ago, 

which covered a similar study highlighting 

the potential of the OspA vaccine, the 

writer was optimistic about 

the vaccine’s release 

in 1995. What happened, then, over these 

three decades? 

LYMErix and The Revival of The OspA 

Vaccine 

According to Fikrig, biopharmaceutical 

company GlaxoSmithKline signed an 

agreement with Yale to develop the 

vaccine. Fikrig and Flavell advised them 

as they developed a three-dose vaccine for 

humans, under the name LYMErix. The 

last phase of clinical trials for the vaccine 

enrolled over ten thousand patients in 

endemic areas, and demonstrated that 

LYMErix was safe and effective in reducing 

the occurrence of Lyme disease in humans. 

Following FDA approval, LYMErix was 

released to the public in 1998. 

Unfortunately, LYMErix’s success was 

short-lived. The vaccine was discontinued in 

2002, even though it remains FDA-approved. 

LYMErix’s brief time on the market saw 

low demand and a potential onslaught 

of lawsuits alleging the vaccine caused 

arthritis. “These rumors were circulating 

that the vaccine was making people sick. 

There was absolutely no evidence for that, 

and there still is absolutely no evidence for 

that,” said Flavell, who is now a Sterling 

Professor of Immunobiology at Yale. 

However, the controversy, combined 

with the lack of interest, was enough for 

GlaxoSmithKline to remove LYMErix 

from the general public. There has not 

been another Lyme disease vaccine for 

humans since then. 

However, that may soon change. Major 

pharmaceutical companies such as 

Pfizer and Valneva are now interested 

in developing a new Lyme vaccine. The 

principle behind how these new vaccines 

would function is similar to findings 

from past research. “You need a high 

titer [concentration] of OspA antibodies 

to work in both [the old and the new 

vaccines] . . . they’re fundamentally the 

same in that regard,” Fikrig said. The new 

vaccines are now being tested in clinical 

trials, offering the possibility that a human 

vaccine for Lyme disease may soon return 

to the market. 



FOCUS 


Beyond Lyme Disease: 

A Vaccine Against Ticks 

While pharmaceutical 

companies try to revive 

OspA vaccine efforts, 

Fikrig and Flavell have moved 

on. They are searching for success with a 

different approach—one that might be able 

to prevent all tick-borne illnesses. Besides 

Lyme disease, Ixodes ticks are also carriers 

of illnesses such as babesiosis, Powassan 

virus, and anaplasmosis, which can cause 

debilitating health effects in humans. Fikrig 

and colleagues utilized an anti-tick approach 

to a vaccine in their recent paper published 

in Science Translational Medicine in 2021. 

The idea of using an mRNA vaccine for tick 

immunity was formulated in 2019 in 

collaboration with Drew Weissman, 

who is now a co-winner of the 

2023 Nobel Prize in Physiology or 

Medicine for his work on mRNA 

vaccine technology (which was 

foundational for the development 

of the Pfizer-BioNTech COVID-19 

vaccine). The mechanism of these vaccines 

relies on the delivery of mRNA, which 

directs the production of a small, harmless 

piece of a target antigen in host cells so that 

the immune system will learn to mount a 

response against them if encountered again. 

Rather than targeting specific antigens 

associated with Lyme disease, the researchers 

focused on the source—proteins found in the 

tick’s saliva, which is secreted into humans at 

the site of the bite. 

After identifying nineteen salivary proteins 

with high immunogenicity (ability to trigger 

an immune response), the researchers created 

a cocktail of mRNA encoding those proteins. 

They placed this cocktail, called 

19ISP, in lipid nanoparticles— 

which protect the mRNA from 

premature degradation—for 

delivery. Two weeks after 

injecting it into guinea pigs, 

antibodies against ten of the 

nineteen proteins were detected 

in the serum of the immunized 

guinea pigs, while none were observed in 

the control group, suggesting that exposure to 

19ISP triggered a humoral response. 

Following this, the guinea pigs then 

underwent tests to examine whether 19ISP 

vaccination was effective in generating tick 

immunity and resistance against Lyme 

disease. “We showed that if you give [19ISP] 

to a guinea pig and then put ticks on it, 

the ticks feed very poorly, you get redness 

where the ticks feed, and the [ticks] detach 

and die quickly. And then we showed that if 

you put ticks that have the disease-causing 

agent in them, the guinea pigs will not get 

Lyme disease,” Fikrig said. 

In comparison, control guinea pigs 

had low rates of tick detachment, did not 

show redness, and were susceptible to B. 

burgdorferi. These results suggest that 

19ISP may be a viable solution in both 

the early detection of tick attachment 

and the facilitation of tick detachment. “I 

think we have a vaccine that can increase 

tick recognition and prevent Borrelia 

transmission,” Fikrig said. “And hopefully, 

at some point, that may be available 

to the public. We don’t know yet, 

but it may be useful in preventing 

more than just Lyme disease.” 

Future Directions 

The “anti-tick” approach is 

crucial because Ixodes represent just one 

genus of ticks that carry illness. Other 

ticks pose their own threats. Saliva from 

Amblyomma ticks, for example, is thought 

to cause red meat allergy in humans, 

according to Fikrig. The tick’s saliva 

proteins may contain the sugar 

molecule alpha-gal, which is 

found in most mammals but 

not in humans. When the tick’s 


saliva is transferred to humans, alpha-gal 

is flagged as a foreign antigen, triggering a 

severe immune response when alpha-gal is 

encountered again, such as in red meat and 

milk. “I think that our anti-tick vaccine can 

be the first ever vaccine against an allergic 

condition,” Fikrig said. In the past, it was 

demonstrated that immunity to Ixodes 

ticks can protect against other diseasespreading 

tick species (e.g. Amblyomma 

and Dermacentor); however, 

their specific 19ISP cocktail 

has yet to be tested for this 

cross-protection. 

In addition to solving 

these mysteries, Fikrig 

and Flavell are working 

with a worldwide network of 

collaborators to explore whether the antiinsect 

approach can be applied to other 

infectious diseases. Flavell highlighted 

that this approach may be applicable 

to other creatures that spread disease. 

“We’ve brought together a consortium 

of people to develop this concept, and if 

we’re very lucky, we could hopefully make 

a dent in diseases like malaria, which is 

a huge problem," Flavell said. Despite 

previous roadblocks in the history of 

Lyme disease vaccines, the researchers 

have continued to forge ahead to meet 

greater success than before—and 

pioneered an approach that 

could revolutionize vaccines for 

allergies and broader infectious 

disease prevention. ■ 

CINDY MEI 

CINDY MEI is a junior in Grace Hopper studying neuroscience. In addition to writing for YSM, she 

serves as vice president on the Junior Class Council and co-director of Yale Math Competitions. She also 

conducts epilepsy and Tourette’s syndrome research at the Yale School of Medicine. 

THE AUTHOR WOULD LIKE TO THANK Erol Fikrig and Richard Flavell for their time and enthusiasm 

about their research. 

CITATIONS: 

Fikrig, E., Barthold, S.W., Kantor, F.S., & Flavell, R.A. (1990). Protection of mice against the Lyme disease 

agent with recombinant OspA. Science, 250 (4980), 553-556. doi: 10.1126/science.2237407. 

Ho, E. (1993) Lyme Disease: Unmasking the Great Imitator. Yale Scientific Magazine, p. 62-64. 

Sajid, A., Matias, J., Arora, G., Kurokawa, C., Deponte, K., Tang, X., Lynn, G., Wu, M., Pal, U., Strank, N.O., 

Pardi, N., Narasimhan, S., Weissman, D., & Fikrig, E. (2021). mRNA vaccination induces tick resistance 

and prevents transmission of the Lyme disease agent. Science Translational Medicine, 13 (620), doi: 

10.1126/scitranslmed.abj9827 


Chemistry 

FOCUS 

REVISITING PFAS 

What 

Happened To 

The “Brilliant 

Future” of 

Forever 

Chemicals? 

BY EVELYN JIANG 

ART BY LUNA AGUILAR 



FOCUS 

Chemistry 

Life on Earth depends on interactions 

between carbon and hydrogen, as 

they come together to form bonds 

that serve as the backbone of many 

organic molecules. However, it is the 

element fluorine that forms the strongest 

single bond with carbon. Chemists tried 

to create these carbon-fluorine bonds in 

the late 1800s, and by the early 1930s, they 

succeeded by replacing hydrogen atoms 

with fluorine in organic molecules. 

Their breakthrough led to the 

development of some of the most resilient 

compounds in organic chemistry today: 

per- and polyfluoralkyl substances, 

or PFAS, which all contain fluorinecarbon 

chains. This extensive family 

of synthetic compounds comprises 

thousands of chemicals known for 

their exceptional durability and 

resistance to degradation, earning 

them the fitting nickname 

“forever chemicals.” 

Since their introduction into 

the market in the 1950s, PFAS have 

been incorporated into a wide range 

of products, from waterproof garments 

to non-stick pans to firefighting 

foam. However, mounting 

evidence indicates that 

these forever chemicals 

have infiltrated not only 

our consumer goods, 

but also our drinking 

water, our soil, and even 

our bodies. 

“A Wonder of Modern Science” 

The birth of PFAS can be traced to the 

so-called “Chemical Century,” which 

witnessed notable advancements in the 

field and the increasingly widespread use 

of synthetic chemicals across society. The 

chemical industry was deeply connected 

to military power and warfare during 

this period. For instance, DuPont’s Teflon 

(polytetrafluoroethylene)—one of the 

most notorious PFAS—was used during 

the Manhattan Project when creating 

warheads, liquid-fuel tanks, and even the 

atomic bomb dropped on Nagasaki in 1945. 

Several of the researchers involved in 

the Manhattan Project would go on to join 

the multinational company 3M to further 

develop PFAS. By 1951, the company began 

producing perfluorooctanoic acid (PFOA), 

a PFAS. PFOA was sent to a DuPont plant 

in Parkersburg, West Virginia, where 

commercial Teflon products would be 

manufactured. Around the same time, 3M 

also began producing Scotchgard, a brand 

of fabric stain and water-repellant sprays, 

using another PFAS called perfluorooctane 

sulfonic acid (PFOS). 

PFAS were also used in Apollo 

space missions and emerging medical 

technologies, as seals on ventilators and 

as a coating for medical catheters. It 

seemed PFAS could be used in everything, 

everywhere, and was heralded as a “wonder 

of modern science.” The optimism of the 

era is reflected in the pages of the May 

1956 issue of the Yale Scientific Magazine 

(Vol. 30 No. 8), which proclaimed that 

“from [Teflon’s] unique characteristics a 

brilliant future can be inferred.” 

Unique Chemical Characteristics 

As past YSM writer Robert J. Lontz laid 

out in that article, PFAS owed its industrial 

desirability to a unique combination of 

properties that made it well-suited for a 

wide range of applications. 

Lontz first pointed out that the strong 

dielectric properties of PFAS make it an 

excellent electrical insulator, capable of 

preventing the flow of electric current 

through the material. Due to the strength 

of its carbon-fluorine bonds, PFAS are 

also chemically inert, meaning they 

remain stable and unreactive when 

subjected to various other chemicals or 

environmental conditions. 

Teflon also offers, as Lontz wrote, a 

“waxy, slippery surface.” PFAS are wellknown 

for their non-stick and lowfriction 

properties, and have thus been 

used to create surfaces that do not adhere 

to other materials, making them easy 

to clean. Finally, PFAS are inherently 

water-repellent. They form a protective 

barrier on surfaces, making them ideal 

for applications such as water-resistant 

clothing or any materials that need to 

repel moisture. 

A Double-Edged Sword 

Nearly seventy years after Lontz’s article 

was published, it has become clear that the 

same unique characteristics that led to PFAS 

being dubbed “forever chemicals” are 

closely intertwined with their 

potential health and environmental 

risks. “Certain members of the PFAS family 

have come to light as biologically and 

environmentally persistent compounds with 

bioaccumulation potential in the last few 

decades,” said Gary Ginsberg, the director 

of the Center for Environmental Health for 

the New York State Department of Health, 

a former member of the EPA’s Science 

Advisory Board, and a clinical professor at 

the Yale School of Public Health. 

In contrast to other persistent organic 

compounds, which primarily accumulate 

in fats, PFAS behave differently. Being 

water-soluble, they can follow natural 

solubility pathways by dissolving in 

water and infiltrating groundwater. This 

dispersal can lead to additional ecological 

impacts, including uptake into fish and 

drinking water supplies. 

In 1998, Wilbur Earl Tennant, a farmer 

from Parkersburg, West Virginia, noticed 

his cows were dying from a mysterious 

illness. He approached lawyer Robert Bilott 

who would go on to investigate the DuPont 

company, whose chemical plant was 

located in the town. By 1999, Bilott filed a 

federal lawsuit against DuPont for dumping 

PFOA waste into local water supplies. In 

April 2003, the Environmental Protection 

Agency (EPA) initiated a comprehensive 

review of the synthetic chemical, raising 

concerns about its prevalence. 

Of particular concern to the EPA was 

the early evidence suggesting that traces 

of PFOA could already be detected in the 

blood of nearly all U.S. citizens. According 

to a study based on 2011-2012 data 

from the National Health and Nutrition 

Examination Survey (NHANES), PFAS 

was detected in the blood of ninety-seven 

percent of Americans tested. 

This statistic becomes all the more 

alarming when considering the wellestablished 

health hazards 

associated with PFAS 

exposure, which include 

20 Yale Scientific Magazine December 2023 

www.yalescientific.org

Chemistry 

FOCUS 

cancer, thyroid disorders, developmental 

issues, and disruptions to the immune 

system. “One of the main drivers for the 

dose-response [of PFAS] seems to be their 

unusual propensity to have long human 

half-lives on the order of three to six 

years,” Ginsberg said. 

Scares & Successes 

Both PFOA and PFOS were phased out 

of production and use in the U.S. in the 

mid-2000s through industry agreements 

with the EPA. Data from the NHANES, 

which has done bio-monitoring work 

since the late 1990s, has shown that levels 

of PFOA and PFOS levels in the U.S. 

population have been declining. Notably, 

blood PFOS levels declined by more than 

eighty-five percent from 1999 to 2018, and 

blood PFOA levels declined by more than 

seventy percent. 

Many state policymakers have been 

increasingly focusing on the issue of 

PFAS, particularly over the past five years. 

Notable actions were taken by Vermont, 

which established maximum contaminant 

levels for PFAS in water, and Minnesota, 

which prohibited specific flame-retardant 

chemicals in furniture and children’s 

products. In 2020 and 2021, states 

continued to address concerns about PFAS 

with numerous bills, targeting regulation 

in firefighting foam, consumer products, 

and drinking water. 

According to Ginsberg, current 

concerns include occupational 

exposures and the toxicology of 

newer generations of PFAS. Krystal 

Pollitt, an associate professor of 

epidemiology at the Yale School of 

Public Health, shared a similar view. 

“One of the challenges with measuring 

these chemicals is that there are over 

ten thousand PFAS and current EPA 

methods only cover about 

twenty of them,” she said. 

Given the known health 

risks associated with PFAS, 

it is perplexing that it took 

until March 2023 for the 

EPA to propose the National 

Primary Drinking Water Regulation 

(NPDWR). If enacted, the NPDWR would 

represent the first national drinking water 

standard for PFAS, imposing enforceable 

limits on levels of six common PFAS 


chemicals—including PFOS and PFOA— 

in drinking water. Unfortunately, this 

much-needed measure arrives far too late 

for many who have already endured the 

adverse effects of PFAS exposure in the 

seven decades since its introduction into 

commercial use. Why did it take so long to 

take federal action against PFAS? 

The Precautionary Principle’s Call 

The heart of the issue lies within our 

regulatory systems. “The challenge lies not 

only in regulating PFAS but in regulating 

any chemical or substance,” Ginsberg said. 

He explained that it has been decades 

since the EPA last determined the need 

for a new maximum contaminant level or 

implemented additional regulations for 

any substance. This is due in part to the 

challenges surrounding implementing new 

regulations and navigating through multiple 

levels of governmental policy review. 

The story of PFAS and the NPDWR 

underscores a disconcerting reality that, 

for decades, there has been a failure within 

regulatory and legislative frameworks 

to proactively address emerging 

environmental and health threats. While 

the EPA is working to be more predictive of 

such threats by employing advanced Toxcast 

testing methods and their Unregulated 

Contaminant Monitoring Rule testing 

program to detect emerging contaminants 

in drinking water, it has become evident 

that creating meaningful change 

within this system is a process that 

takes time. 


“The optimal way forward 

would be to regulate PFAS 

as a class,” Pollitt said. As 

of now, researchers 

including Pollitt 

are still working 

to understand 

the health 

impacts of PFAS. T h e y 

employ various methods, such 

as measuring PFAS levels in biological 

samples and collaborating with numerous 

epidemiologists to develop scalable 

solutions for assessing exposure. Had the 

precautionary principle, which advocates 

that a substance be proven safe before being 

released into the market, been integrated 

into our regulatory framework, this could 

have been a different story. We would not 

only foster a culture of prevention rather 

than reaction, but also show that public 

health and environmental safety take 

precedence over economic interests. 

The story of PFAS serves as an urgent 

call for change and as a stark reminder 

of what can happen when scientific 

innovation goes unchecked. And this story 

is not unique. “Look at pesticides and 

DDT; it was only after decades of broad 

use without appropriate safety testing 

and risk assessment when they were then 

phased out,” Ginsberg said. “PFAS is just 

one example of us not doing our homework 

before releasing chemicals to the market.” ■ 

EVELYN JIANG 

EVELYN JIANG is a sophomore in Morse College majoring in neuroscience. In addition to writing for 

the YSM, she works at Yale’s Alzheimer’s Disease Research Unit and the Koleske Lab. 

THE AUTHOR WOULD LIKE TO THANK Krystal Pollitt and Gary Ginsberg for their time and 

enthusiasm in sharing their expertise. 

FURTHER READING 

Savvaides, T., Koelmel, J. P., Zhou, Y., Lin, E. Z., Stelben, P., Aristizabal-Henao, J. J., Bowden, J. A., & Godri 

Pollitt, K. J. (2021). Prevalence and Implications of Per- and Polyfluoroalkyl Substances (PFAS) in Settled 

Dust. Current environmental health reports, 8(4), 323–335. https://doi.org/10.1007/s40572-021-00326-4 


FOCUS 

Gene Therapy 

RIGHT IDEA, 

WRONG TARGET? 

Gene Therapy For Parkinson's Disease 

BY MADELEINE POPOFSKY AND RISHA CHAKRABORTY 

ART BY JUNGBIN CHA 


Gene Therapy 

FOCUS 

Why do treatments fail? 

Sometimes there is an issue 

with the treatment’s target. 

Other times, the translation from an 

animal model to humans presents too big 

of a gap. Over the history of research on 

gene therapy, such failures have brought 

scientists closer to success. 

The idea behind gene therapy is to treat 

genetic diseases at their source by altering 

a missing or faulty gene. For Parkinson’s 

disease—in which loss of dopamineproducing 

(dopaminergic) neurons leads 

to slowness of movement and other severe 

motor symptoms in late stages—this 

approach has shown promise, but success 

has, thus far, been out of reach. 

Past research on gene therapy had 

targeted a part of the basal ganglia—which 

is responsible for motor control—called 

the striatum. In mouse models, this was 

quite successful, and several papers were 

published on different genes targeting this 

area. One of these papers, published in 1994, 

was covered in the Yale Scientific Magazine 

by Gautam Mirchandani (Vol. 66 No. 2), who 

called it a promising study. The proposed 

therapy was designed to target the gene for 

tyrosine hydroxylase (TH), an enzyme that 

is critical for synthesizing dopamine in a 

Parkinson-like disorder. “Hopes are that 

such a treatment will soon be available for 

human benefit,” Mirchandani wrote. Yet, 

these techniques have all since failed. 

The problem, in many of these cases, was 

actually the target. While easy to target in 

a mouse, the basal ganglia in humans has 

enlarged dramatically over the course of 

evolution. Since the striatum forms such a 

large part of the basal ganglia’s structure, it 

was simply too large of a target. “It is very 

difficult to cover it by injecting a virus,” said 

Jim Surmeier, a professor of neuroscience at 

Northwestern University Feinberg School of 

Medicine. He is one of the many scientists 

taking up the task of turning the coal of past 

failures into the future diamonds that will 

let gene therapy shine. “We fail more often 

than we succeed,” Surmeier said. “What 

distinguishes really good researchers is the 

ability to learn from your failures.” 

A New Target? 

Surmeier’s research challenges prevailing 

theories regarding the function of 

dopaminergic neurons and their site of 

action in Parkinson’s disease. Previous 

researchers had assumed that loss of 

dopamine in the striatum was sufficient 

to cause the primary motor symptoms 

associated with Parkinson’s. However, 

Surmeier developed a new animal model 

for Parkinson’s that involved 

disrupting Complex 1, an 

important protein for 

energy generation, in 

the mitochondria 

of dopaminergic 

neurons. The 

difference in this 

model was that, 

unlike most 

animal models 

for Parkinson’s 

which cause 

rapid onset of 

the severe motor 

symptoms, this 

model more closely 

mimicked human 

Parkinson’s with its slow 

onset. Motor symptoms only became 

apparent several months after gene editing. 

This more realistic model led to both a new 

potential cause of Parkinson’s in humans 

and a better lens through which to study 

how brain circuits contribute to the disease. 

Using this model, Surmeier discovered 

something unexpected. “When there was 

clear loss of striatal dopamine release, the 

animals were not Parkinsonian, contrary 

to the prediction of the classical model,” 

Surmeier said. His new theory takes into 

account the structure of the basal ganglia. 

While the striatum is a large complex within 

this structure, there are other nuclei— 

clusters of neurons that perform a specific 

function—modulated by dopaminergic 

neurons. One of these, which sits between 

the basal ganglia and the rest of the brain, 

is the substantia nigra pars reticulata (SNr). 

While the traditional model of Parkinson’s 

focuses on almost solely treating the 

striatum, Surmeier proposed the SNr as 

a new target for gene therapy. “The basal 

ganglia are organized like a funnel, with the 

SNr at the mouth of the funnel. Targeting 

the mouth of the funnel is the best way to 

control the output of the basal ganglia,” 

Surmeier said. 

Now armed with a location, Surmeier 

needed a gene. In his study published in 

Nature in 2021, he targeted aromatic acid 

decarboxylase (AADC), a key enzyme that 

converts the precursor levodopa into its final 

form of dopamine. Levodopa is commonly 

used as a treatment for Parkinson’s. 

However, its effects wear off with time and 

more advanced forms of the disease since 

the dopaminergic neurons that 

are dying are the primary 

producers of AADC. 

Thus, over time, the 

brain begins to lack 

sufficient AADC to 

convert levodopa 

into dopamine. 

In this trial in 

mice, Surmeier 

was able to use 

gene therapy to 

give a new group 

of neurons the 

ability to express 

A A D C — t h o s e 

in the SNr—which 

relieved motor deficits in 

Parkinsonian mice. 

Throughout the process, Surmeier 

emphasized that one has to be willing to 

both challenge past assumptions and learn 

from past failures. When he first received 

the data from his new Parkinsonian model, 

Surmeier was skeptical enough to ask 

others to repeat similar experiments, again 

and again, when his results did not match 

preconceived notions. “In science, we never 

have truth in our hands,” Surmeir said. “It is 

always an approximation.” 

Yet Another Target? 

Surmeier’s work is only the tip of the 

iceberg when it comes to developing 

gene therapies for previously intractable 

diseases. His successful process of choosing 

just the right nucleus for targeting, and just 

the right enzyme to target for modification, 

is the result of not just personal failures, but 

also the failures, and successes, of many of 

his colleagues. 

One such colleague is Krzysztof 

Bankiewicz at the Ohio State College of 

Medicine. Bankiewicz has been interested in 

dopamine and Parkinson’s disease since the 

1980s, when he joined one of the first clinical 

trials to restore normal dopamine levels in 

the brain to reverse Parkinsonian symptoms. 

The clinical trial intended to transplant 

cells that could produce dopamine into the 



FOCUS 

Gene Therapy 

Striatum 

Basal ganglia 

Substancia nigra 

pars reticulata 

striatum. But despite trying many stem and 

fetal cell lines, many dopaminergic cells did 

not survive the transplantation process. It 

did not seem like cell transplantation was 

going to work. 

The advent of gene therapy, where a 

clinician can change just one gene at a time 

as opposed to transplanting entire new cell 

lines, was exciting to Bankiewicz. He began 

studying specific gene-delivery systems 

and experimenting with different targets in 

the brain for the delivery of enzymes that 

could convert levodopa into dopamine. 

He also tried many variations of the viral 

vector, which is used to deliver a properly 

functioning copy of a gene in gene therapy. 

After twenty years of repeated failure and 

learning, he has managed to launch clinical 

trials intended to deliver genes of interest 

to treat many neurodegenerative diseases, 

such as pediatric Parkinson’s disease. He 

looks at commonalities between diseases 

to figure out the best way to approach 

new ones. “In this way, the disease itself 

becomes more of an application for the 

operating systemsystem," Bankiewicz 

said. The operating system is the common 

pipeline that enables him to optimize a 

gene therapy’s chance of clinical success. 

Bankiewicz is currently trying to develop 

gene therapies for neurotrophic factors, 

which are proteins in the brain that support 

the development and maintenance of 

neurons (since neuronal damage and death 

characterizes various dementias). He has 

worked on increasing the production of the 

protective brain-derived neurotrophic factor 

to the entorhinal cortex, a key memory 

center in the brain, to slow and possibly even 

reverse memory loss in Alzheimer’s disease. 

He is currently working on a trial to increase 

the production of glial-derived neurotrophic 

factor that promotes dopaminergic neuron 

survival, which may ameliorate Parkinson’s 

disease symptoms. He says 

that there are other diseases 

to address through the 

neurotrophic factor pathway, 

including Huntington’s disease 

and childhood dementias. 

Bankiewicz’s theory also 

supports the development of various gene 

therapies to reduce and replace proteins 

that misfold and aggregate in various 

neurodegenerative diseases. For example, 

he is currently working on a trial to reduce 

levels of alpha-synuclein, which accumulates 

in Parkinson’s disease and multiple system 

atrophy, and is interested in developing a 

trial to replace the protein progranulin which 

leads to amyloid protein accumulation in 

patients with fronto-temporal dementia. 

Bankiewicz’s research is especially 

important because gene therapy can be a 

highly effective treatment that works for most 

patients, regardless of their disease etiology. 

This means that it does not matter whether a 

patient has a genetic cause for their disease 

or if their disease is idiopathic (unknown 

cause). For example, when patients are 

given levodopa, the drug addresses their 

symptoms regardless of the cause of their 

ABOUT THE 

AUTHORS 

Parkinson’s disease. Similarly, gene therapy 

addresses common disease pathology, such 

as loss of dopaminergic neurons or levodopa 

resistance in Parkinson’s disease, regardless of 

whether it is driven by idiopathic or familial 

factors. This means it has a higher chance of 

working across patient populations. 

Moreover, gene therapy is a one-time 

surgical treatment, which is clinically 

preferable for patients, whose alternatives are 

either to live with a deep-brain stimulation 

electrode within their head, spend the 

rest of their life taking a medication that 

progressively loses its effectiveness, or 

let their disease continually advance. 

Bankiewicz stated that his patients feel safe 

undergoing the treatment, knowing that 

its effects are very localized. “They love the 

idea of just getting one therapeutic for life,” 

Bankiewicz said. 

This field has made significant leaps since 

YSM last reported on the 1994 study on gene 

therapy. Bankiewicz’s and Surmeier’s clinical 

trials may bring treatment to hundreds of 

thousands of people who would otherwise 

live without the hope of recovering from 

or surviving their disease. Yet all this would 

not have been possible without countless 

mistakes. If Bankiewicz has learned one 

thing along the way, it is that scientists are 

hardly right every single time. “One lesson 

that I tell my students and scientists: don’t 

be afraid to try. You learn from your failures. 

So, don’t be afraid to fail,” he said. ■ 

MADELEINE POPOFSKY 

RISHA CHAKRABORTY 

MADELEINE POPOFSKY is a sophomore Neuroscience major in Pauli Murray College. In addition to 

writing and doing graphic design for YSM, she debates in the Yale Debate Association, directs visual arts 

for Hippo Magazine, and volunteers for JDRF. 

RISHA CHAKRABORTY is a third-year Neuroscience and Chemistry major in Saybrook College. In 

addition to writing for YSM, Risha plays trumpet for the Yale Precision Marching Band and La Orquesta 

Tertulia, volunteers at YNHH, and researches Parkinson’s disease at the Chandra Lab. 

THE AUTHORS WOULD LIKE TO THANK Dr. Jim Surmeier and Dr. Krzysztof Bankiewicz for their time 

and enthusiasm for their research. 

FURTHER READING: 

González-Rodríguez, Patricia, et al. “Disruption of Mitochondrial Complex I Induces Progressive 

Parkinsonism.” Nature, 3 Nov. 2021, pp. 1–7, www.nature.com/articles/s41586-021-04059-0. 

Pearson, Toni S., et al. “Gene Therapy for Aromatic L-Amino Acid Decarboxylase Deficiency by MR- 

Guided Direct Delivery of AAV2-AADC to Midbrain Dopaminergic Neurons.” Nature Communications, 

vol. 12, no. 1, 12 July 2021, p. 4251, www.nature.com/articles/s41467-021-24524-8. 

Christine CW, Richardson RM, Van Laar AD, Thompson ME, Fine EM, Khwaja OS, Li C, Liang GS, Meier 

A, Roberts EW, Pfau ML, Rodman JR, Bankiewicz KS, Larson PS. Safety of AADC Gene Therapy for 

Moderately Advanced Parkinson Disease: Three-Year Outcomes From the PD-1101 Trial. Neurology. 

2022 Jan 4;98(1) 


FASTER THAN 

Physics 

FEATURE 

LIGHTSPEED 

THESE NEUTRINOS WERE FASTER THAN THE SPEED OF LIGHT— 

UNTIL THEY WEREN’T 

Physics-bending findings. Irreproducible results. In 2011, 

news of neutrinos, neutral particles with infinitesimal 

mass, traveling faster than the speed of light topped science 

headlines, prompting widespread debate about the truth of these 

findings. The debate stemmed from the fact that Einstein’s theory 

of special relativity says nothing can travel faster than light. But the 

Oscillation Project with Emulsion-tRacking Apparatus (OPERA) 

experiment at the underground Gran Sasso Lab (LNGS), had 

measured the velocity of neutrinos to be 0.0024 percent faster than 

lightspeed, contradicting Einstein. If OPERA’s results were true, a 

core theory of physics would be shaken. 

The premise of this measurement was simple: send a beam of 

neutrinos 730 kilometers from the European Organization for 

Nuclear Research (CERN) to the OPERA detector at LNGS and 

measure their time of flight. Yet, OPERA’s primary goal was not 

to measure neutrinos’ speed. The researchers conducted the 

additional measurement because OPERA was well suited to 

accurately determine neutrino velocity. The OPERA experiment 

had primarily been designed to test the phenomenon of neutrino 

oscillations, which occur when neutrinos oscillate between three 

known “flavors”: electron, muon, and tau. Located at the LNGS, the 

OPERA system aimed to be the first to detect the 

appearance of tau-neutrinos from the oscillation of 

muon-neutrinos during the 2.4-millisecond trip 

from CERN to Gran Sasso. 

The researchers exhaustively checked every part of 

the experiment that could have caused the unexpectedly 

fast neutrino speed. They debated whether the research 

should be made public. Some didn’t think the checks and 

tests on the equipment and experimental methods had 

been exhaustive enough. “I was skeptical—almost sure 

it was wrong,” said Laura Patrizii, a member of 

the OPERA Collaboration. Putting it to 

a vote, the researchers who pushed 

for sharing their potentially 

revolutionary findings won out. 

However, since many 

working on the project 

maintained that something had 

gone wrong, the Collaboration 


BACKGROUND IMAGE COURTESY OF BERKELEY LAB 

BY GENEVIEVE KIM 

didn’t submit for publication in a scientific journal and instead posted 

to arXiv.org, a non-peer-reviewed open-access archive. Meanwhile, 

the OPERA researchers continued to investigate still-unknown 

systematic effects that could explain the anomalous result. 

“Exceptional results require exceptional checks,” Patrizii 

said, paraphrasing Carl Sagan, astronomer and famous science 

communicator. OPERA’s error-searching efforts proceeded in tandem 

with labs across the world that tried to replicate the results—to no avail. 

Other research groups noted that if the neutrinos were truly traveling 

at light-surpassing speed, they should have also been releasing energy. 

But no trace of this energy was seen in the experiment, increasing doubt 

about the measurements. 

In 2012, OPERA finally disproved its own findings. The Collaboration 

found that there were two sources of error that had caused the observed 

relativity-defying speed. First, a connector measuring the time delay 

from a GPS receiver to the OPERA Master Clock was faulty, and 

second, the frequency of the Master Clock was out of specification. The 

researchers had calibrated the connector when it was securely plugged 

in, but during the experiment it had been partially disconnected, 

resulting in a distortion and delay of the signal. After the time delay was 

calculated and accounted for, the neutrino interactions with OPERA 

lagged by sixty nanoseconds. The neutrinos hadn’t actually traveled 

faster than the speed of light—the timing itself was incorrect. The search 

for an explanation was finally over. 

In 2014 and 2015, OPERA papers shared the neutrino oscillation 

data. Like all other findings from CERN, they underwent multiple 

reviews and screenings before being released to the public. Today, 

the common worldwide policy for peer review even bans graduate 

students conducting research at CERN from including figures made 

for their own research in any university papers if the figures involve 

CERN projects that have not been finalized. Any results they do share 

from a non-finalized project leave CERN marked as “preliminary.” 

This rigorous peer-review process reflects how the scientific process 

preserves scientists’ credibility, just as researchers around the world 

constructively critiqued the neutrino speed findings. 

“The ‘case’ of superluminal neutrinos is frequently referenced as an 

example of how science operates, highlighting the effectiveness of the 

scientific method and its provando e riprovando (trying and trying again) 

approach,” Patrizii said. “Science is not a belief system; it operates without 

dogma.” The researchers’ desire to ensure their findings’ validity, even 

if it would negate what would otherwise be a groundbreaking finding, 

shows the scientific community’s dedication to better understanding the 

universe. This case of the too-fast neutrinos, rather than being a scientific 

failure, was actually an example of the success of the scientific process. ■ 


FEATURE 

Oceanography 

SEAWATER 

SQUABBLES 

BY BRANDON NGO 

OVERTURNING A 130-YEAR- 

OLD ASSUMPTION IN 

SEAWATER CHEMISTRY 

ART BY ANNA OLSZOWKA 

Look back on the beaches you’ve been to in the past 

decade. The serene sand, the soothing warmth of the 

sun, and most importantly, the refreshing splashes of the 

ocean waves. That same seawater may have contributed to a 

recent study that has overturned years of research. For over a 

century, scientists believed that charged particles, called ions, 

in seawater remained in relatively similar ratios across the 

ocean. However, a group of researchers have debunked this 

assumption, leading to concerns about the accuracy of past 

seawater studies that depended on it. 

Mario Lebrato, a station manager and chief scientist at the 

Bazaruto Center for Scientific Studies in Mozambique, led 

the team that challenged this assumption about seawater ion 

proportions. Interestingly, the original intent of their study wasn’t 

to test this assumption. “Originally, we were trying to understand 

how plankton grew in different seawater conditions,” Lebrato 

said. His research team organized seawater samples from different 

parts of the world to analyze plankton growth. After measuring 

the composition of a few samples, Lebrato noticed significant 

differences in ion proportions between seawater from different 

sources. “This really triggered the project,” he said. 

“It all started with the question of: why are these waters so 

different in terms of oceanic versus coastal?” Lebrato said. To 

further their investigation, his team organized partnerships with 

international universities, governments, and environmental 

agencies over seven years. They knew it would be hard to 

collect seawater samples worldwide without outside assistance 

or substantial funding. “It’s almost impossible for anybody to 

organize over a hundred research cruises,” Lebrato said. These 

partnerships ranged from organizations like the United States 

National Oceanic and Atmospheric Administration (NOAA) and 

Environment Canada, to small research cruises and individual 

scientists. Lebrato even received help from organizations that 

ventured into the Arctic Circle to retrieve seawater samples. 

At the end of their seven-year project, Lebrato’s team concluded 

that the original assumption about ion proportions in seawater 

was incorrect. According to Lebrato’s research, there were 

significant deviations in major seawater ion ratios between 

samples, specifically in the open ocean. “Everybody knew it was 

expected to find deviations from the coast, deviations near the 

rivers, and deviations in the poles near the ice. But nobody was 

expecting significant deviations on the open ocean,” Lebrato said. 

Upon discovering this flaw in this then-long-standing 

assumption on seawater ion ratios, Lebrato was initially worried 

about the international reaction to his team’s research. “I was prestressed 

because I was like, okay, maybe we’re doing something 

wrong,” Lebrato said. In the final stages of the research project, 

Lebrato’s team rechecked all of the data with the owners of the 

labs, ensuring the results were consistent. They remeasured 

open ocean samples up to five times to validate their results. 

After the researchers published the project, the international 

science community accepted the discovery. Lebrato was 

especially pleased with these results. 

However, Lebrato’s group of researchers could not pinpoint all 

of the exact causes for these deviations in ion ratios. It’s possible 

that ocean and earth processes—such as weathering, evaporation, 

particle movement from ocean waves, and ion production from 

sea animals—contribute to these variances in the ion ratios of 

seawater. However, it is difficult to isolate the exact reasoning 

without further work. “The research basically opened a Pandora’s 

box for people to start revising the topic and doing experiments 

on it,” Lebrato said. After their paper was published, a wave of 

research proposals formed, with some looking to explore the 

cause of these varying ion ratios. Other research proposals looked 

to reevaluate the accuracy of past papers that relied on the nowoverturned 

assumption. 

It’s important to keep in mind that overturning assumptions 

is necessary in scientific research and isn’t a way to target other 

researchers. “We’re not pointing fingers at anybody,” Lebrato 

said. Instead, by debunking this assumption, new research 

opportunities have arisen to further investigate ocean chemistry. 

Revising and experimenting with these assumptions is a natural 

part of the research process and plays a crucial role in maintaining 

accuracy in the vast expanses of scientific literature. ■ 


Chemistry 

FEATURE 

THIS METAL-FREE REACTION 

CONTAINS . . . METAL 

Eliminating Palladium from the Suzuki Reaction 

BY LAWRENCE ZHAO 

It was the right time for a breakthrough, but was it too good 

to be true? In early 2021, a research group led by Professor 

Hua-Jian Xu at the Hefei University of Technology claimed 

to have found a new, nitrogen-based catalyst for the Suzuki 

reaction. The Suzuki reaction is a popular method among 

organic chemists to create new bonds between two carbon 

atoms, and in the past, it has always involved a palladium 

catalyst—a substance that speeds up a chemical reaction. 

However, researchers want to stop using palladium because 

the metal is toxic, difficult to recycle, and expensive, which 

limits their ability to use the Suzuki reaction to synthesize 

compounds in industry. Since 2003, scientists have promised 

a metal-free Suzuki reaction, but each time, they’ve found 

evidence of palladium contamination in their attempts. Mere 

traces of palladium on a dirty stir bar could be enough to start a 

Suzuki reaction, so researchers must be extra careful that there’s 

no palladium at all. 

So, when the scientific community heard about Xu’s claims 

of a palladium-free Suzuki reaction, they were immediately 

skeptical. Although the Xu group included safeguards to avoid 

palladium contamination, scientists on X (formerly Twitter) 

quickly pointed out that Xu had used a palladium compound 

to make their Suzuki catalyst. Could palladium have somehow 

snuck into Xu’s experiment, just like his predecessors’? 

Chemistry professor Robin Bedford at the University of Bristol 

has been working with catalysts for over 30 years. “I was one 

hundred percent confident that it was palladium-catalyzed, 

and I needed [more evidence] to be shifted from that position,” 

Bedford said. 

Bedford contacted other scientists who had doubted Xu’s 

work on social media and asked if they would join him in 

investigating his hunch that palladium contamination was at 

fault. After assembling a team of investigators, Bedford tried to 

figure out what might have gone wrong. To Bedford’s surprise, 

everything Xu did was reproducible to a remarkable degree— 

the numbers were within one to two percent of reported values, 

which is an unusual feat for synthetic chemistry. However, the 

main issue lay in what Xu didn’t do—a control experiment that 

created the catalyst without using palladium. When Bedford 

used a different, palladium-free route to make Xu’s catalyst, the 

catalyst no longer worked as advertised. Bedford did further 

testing which revealed that the metal was hiding in plain sight. 

ART BY KARA TAO 

Pd 3+ 

It turned out that palladium had nestled itself 

in a stable compound that made it challenging 

to detect. Xu used a process that was unable to 

extract the palladium from these compounds, 

leading him to believe there wasn’t any 

palladium in the catalyst. However, when 

Bedford and his collaborators subjected it 

to hot, concentrated acid, the metal broke 

free. Unfortunately, Xu’s palladiumfree 

Suzuki coupling wasn’t so 

palladium-free after all. Nine 

months after Xu’s initial 

announcement, Nature 

Catalysis published 

the concerns that 

researchers like Bedford 

had voiced. In response 

to growing doubt, Xu 

swiftly retracted his paper. 

Although Xu failed to make a 

metal-free Suzuki reaction, his story is actually 

an example of success in the scientific method. “The scientific 

method is predicated on failure,” Bedford said. Science tends to 

fall in line with existing beliefs, but Xu pushed the boundary 

of what was conventionally thought to be possible. Because Xu 

had to retract his work, the research may seem to be, at first 

glance, reprehensible. In reality, his effort to expand the breadth 

of human knowledge is admirable. Retractions carry a negative 

stigma in the scientific community because they often arise 

from papers with manipulated data. To encourage scientists to 

retract papers with errors made in good faith, Bedford suggests 

creating a separate distinction for papers like Xu’s. 

Bedford continues to search for new sustainable pathways 

to synthesize organic molecules. He is currently in the midst 

of publishing a proof-of-concept of an iron-catalyzed Suzuki 

coupling. Backed by almost 400 pages of data, Bedford’s 

efforts underscore just how difficult it has been to eliminate 

palladium from the Suzuki reaction. While his work may not 

be more efficient than currently available procedures, it’s a big 

step towards replacing palladium once and for all. One day, 

we might be able to cheaply make life-saving pharmaceuticals 

using a metal-free Suzuki reaction. ■ 

Zn 2+ 



FEATURE 

Special Profile 

FROM 

“NOT GOOD ENOUGH” 

TO NOBEL PRIZE WINNER 

KATALIN KARIKÓ'S PERSISTENT JOURNEY TO DEVELOPING THE MRNA VACCINE 

BY ANNLI ZHU & MICHAEL SARULLO | ART BY LUNA AGUILAR 

Early in her career, Katalin Karikó 

was confronted with a dilemma. 

As a researcher at the University 

of Pennsylvania, she had struggled to 

secure grant money and was faced with an 

ultimatum: either leave the university and 

abandon any hopes of becoming a tenured 

faculty member, or receive a demotion, 

setting her career back by years. It seemed 

that Karikó’s deep interest in mRNA would 

soon see its end. What followed, instead, is 

a story of incredible persistence, dedication, 

and brilliance. 

Beginning in the 1960s, scientists had 

connected the dots of DNA’s role in protein 

synthesis—the process responsible for almost 

all cellular functions—and mRNA was the 

critical missing piece. Short for messenger 

RNA, this helical strand of molecules 

represents DNA in a portable manner, 

allowing for information from the nucleus of 

the cell to be delivered to ribosomes where 

protein synthesis can occur. 

By the 1970s, the concept of synthetic 

mRNA—custom-created in the lab and 

introduced into the cells of patients—created 

the prospect of initiating healing processes 

from within cells. Immediately, the possible 

range of applications seemed endless: could 

mRNA revolutionize vaccine development 

by prompting cells to produce key antibodies 

against convoluted viral infections? Could 

mRNA therapy enhance the immune system’s 

abilities to detect and eliminate cancerous 

cells? Karikó’s fascination with the potential 

of mRNA therapy inspired her life’s research 

within the field, making the University 

of Pennsylvania’s disregard of her work 

absolutely crushing. To better understand 

why, we must start from the beginning. 

Katalin Karikó’s career in science began at 

the University of Szeged in her native Hungary, 

where she first learned about viruses and 

mRNA. There, she found herself surrounded 

by peers who seemed more academically 

prepared, whether more experienced in the 

lab or more fluent in English. In her recently 

published autobiography, Breaking Through: 

My Life in Science, Karikó reflects on her 

time at university and playing catch-up with 

her peers. “If I have any superpower, it has 

always been this: a willingness to work hard 

and methodically, and refuse to stop,” she 

wrote. This superpower would prove to be 

indispensable throughout her life. 

In 1985, the company that had funded 

Karikó’s postdoctoral research terminated 

her role. Following many fruitless attempts 

to secure a funded position across Europe, 

Karikó finally found an opportunity to 

continue her research at Temple University 

in Philadelphia. She arrived in America with 

her husband, her daughter, and $1,200 in 

cash sewn into the stuffing of her daughter’s 

teddy bear. 

While Karikó’s work was going well, her 

supervisor proved to be hostile, threatening 

to revoke her visa if she left his lab. But 

Karikó was determined to stay in America, 

and where there’s a will, there’s a way. In 

1989, she found a position in the cardiology 

clinic at the University of Pennsylvania’s 

medical school as a biochemist surrounded 

by doctors. “Working among MDs [gave 

me] the thing I valued most: a chance to 

learn,” Karikó wrote. “Besides, when hadn’t 

I been a fish out of water?” 

At first, her experience at UPenn was 

very positive. Alongside her boss, Dr. Elliot 

Barnathan, Karikó worked on using mRNA 

to deliver proteins that would reduce the 

risk of blood clots in target areas, and 

she became even more convinced of the 

potential of her research. 


Special Profile 

FEATURE 

IMAGE COURTESY OF WIKIPEDIA COMMONS 

Mural of Karikó located in Budapest, Hungary. 

Unfortunately, this conviction was not 

shared by many. A critical metric for scientific 

success was—and still is—attracting funding, 

and Karikó had been repeatedly rejected by 

grants that deemed her research too risky and 

slow. “I published more slowly than others,” 

she explained. “I didn’t want my scientific 

papers to be rushed. I didn’t want to be so 

eager to publish that I risked contaminating 

the scientific literature with dubious results.” 

Karikó found UPenn to be increasingly 

impatient with her lack of funding and as a 

result, dismissive of her work. “I was learning 

that succeeding at a research institution like 

Penn required skills that had little to do with 

science,” she wrote. “You needed the ability to 

sell yourself and your work.” 

In January 1995, Karikó was diagnosed 

with breast cancer. Soon after, her husband 

was forced to stay in Hungary due to visa 

complications. This time also marked five 

years since she joined UPenn, and per 

university policy, she must either be demoted 

or leave. Faced with a difficult decision at one 

of the most difficult points in her life, Karikó 

nonetheless stayed true to her scientific 

calling, taking the demotion in order to 

continue her mRNA research. 

Two years later, Karikó met Dr. Drew 

Weissman, an immunologist who had just 

joined the university. Weissman was interested 

in vaccines, and Karikó had just the expertise 

he needed to deliver antigens—molecules 

that trigger an immune response against 

viruses—with mRNA. The pair discovered 

that, by slightly altering one base nucleotide, 

they could safely administer mRNA without 

causing a negative inflammatory reaction. 

When combined with Karikó’s previous work 

on mRNA delivery, the team had the final 

piece of the puzzle. 

The pair excitedly submitted their mRNA 

vaccine research to Nature—but their paper 

was rejected as merely an “incremental 

contribution.” When they finally convinced 

another journal to publish their work, it 

gained little attention. 

Meanwhile, UPenn was again getting 

impatient, citing Karikó’s continued inability 

to secure funding. “[All they cared about 

was] dollars per net square footage,” she 

wrote. “The fact was, I barely cost this 

department anything… my salary was 

laughable compared with the neurosurgeons 

who surrounded me… I had no staff, no 

postdocs… I wasn’t even a faculty member!” 

When she appealed for her faculty position 

to be reinstated, the department responded 

that she was “not of faculty quality.” 

Fortunately, with their research finally 

published, Karikó and Weissman’s 

mRNA vaccines were recognized by a 

few. Realizing that UPenn was not going 

to support their work, the pair licensed 

their technology to the then-little-known 

BioNTech, where Karikó assumed the 

role of vice president in 2013. Working in 

industry was refreshing, Karikó explained. 

“It didn’t matter whether you spoke with 

an accent, or whether you’d attended an 

“It didn’t matter whether you spoke with an 

accent, or whether you’d attended an Ivy League 

school, or if you were good at schmoozing.” 

Science was science. 

Ivy League school, or if you were good 

at schmoozing.” Science was science. 

Then, in early 2020, all eyes turned 

towards the novel coronavirus. Suddenly, 

vaccine development was required at 

an unprecedented scale and speed, and 

BioNTech was at the forefront. The Pfizer- 

BioNTech vaccine’s phase III trials came 

back successful within a year, making 

Karikó a hero. After decades of obstacles, 

threats of deportation, demotions, and 

rejections, her superpower—a fierce belief 

in her research and refusal to stop at any 

cost—finally helped her realize her dream. 

On October 2, 2023, Katalin Karikó and 

Drew Weissman were awarded the Nobel 

Prize in Physiology or Medicine for their 

work on mRNA vaccines. 

UPenn immediately acknowledged 

Karikó’s and Weissman's Nobel Prize, 

coining them “Penn's historic mRNA 

vaccine research team” in a social media 

post (later marked as “misleading” due to 

Karikó’s lack of affiliation with the university 

over the past decade), accompanied by a 

press release that failed to mention Karikó’s 

difficult history with the university. The 

post drew criticism from prominent 

members of the medical and scientific 

communities. One assistant professor 

from Stevenson University commented, 

“A woman winning the Nobel Prize for the 

same work Penn called ‘not faculty quality’ 

& Penn CLAIMING CREDIT is exactly 

how misogyny in academia works.” 

Indeed, Karikó’s journey underlines 

prominent issues in academia. UPenn’s 

self-congratulatory post highlights their 

attempt to mask their poor treatment 

and lack of support, while exemplifying 

the institutional desire to prioritize profit 

over genuine, innovative research. Finally, 

Karikó’s narrative serves as an important 

reminder of the repeated undervaluation 

of women’s work in science. While Karikó’s 

story is one of triumph, it is important to 

call attention to the many shortcomings 

present in academia and to create an 

environment supportive of scientific 

innovation. In Karikó’s words: 

“We can do better. Science, at its best, is 

about asking questions, trying things, and 

going wherever that inquiry takes you. It 

requires walking into the unknown—the 

unknown is the very point!” ■ 



FEATURE 

Astronomy 

BY WILLIAM ARCHACKI 

ART BY JUNGBIN CHA 

PROVOCATIVE BIOSIGNATURE DATA CREATES ASTRONOMICAL DISCORD 

The story goes that Isaac Newton was 

contemplating the orbit of the Moon 

when an apple fell on his head, and— 

eureka! His theory of universal gravitation 

was born. Historians say this story about the 

apple is dubious, but it’s still woven into the 

mythos of science because it illustrates how 

an unexpected observation can transform 

the way scientists understand an idea. A 

surprising insight, and presto, new science— 

it sure worked in Newton’s time. 

So now imagine you’re Jane Greaves, a 

planetary astronomer at Cardiff University 

in Wales, and after eighteen months of 

crunching data from observations made 

in June 2017 on the James Clerk Maxwell 

Telescope in Hawai‘i, you’ve convinced 

yourself of the impossible—that you and 

your team have detected a signature of life 

emanating from the warm clouds of Earth’s 

seemingly desolate neighbor Venus. Finding 

alien life might be as 

simple as looking 

next door. The apple 

has fallen. What 

comes next? 

As indicators of 

life go, this signal 

from Venus was about as good as it gets. 

Greaves and her colleagues had detected 

a relatively small concentration of the 

gas phosphine, which is a molecule made 

of a phosphorus atom bonded to three 

hydrogen atoms. Astrobiologists call it a 

“biosignature gas.” With limited exceptions, 

it is only produced by life. On Earth, 

anaerobic bacteria that live underwater 

are the only organisms known to partake 

in the strange and challenging chemistry 

required to produce something as peculiar 

as phosphine. And scientists in labs aren’t 

much better: there is no known chemical 

mechanism by which phosphine can be 

produced without temperatures far more 

extreme than those found on Earth and 

Venus. If the phosphine in the atmosphere 

of Earth can only be created through life, is 

the same true on Venus? 

Encouraged by the results of their first 

observation, Greaves and her colleagues 

wasted no time to observe the Venusian 

atmosphere again with a more advanced 

telescope in March 2019. This time, they 

used the Atacama Large Millimeter Array 

radio telescope (ALMA) in Chile. Like the 

first telescope, ALMA recorded the intensity 

of radiation coming from Venus at different 

frequencies and performed a complex 

series of calculations to produce data that 

scientists could interpret, like a fingerprint 

for the concentrations of various gases. Once 

again, Greaves and her colleagues calculated 

a statistically significant concentration of 

phosphine in the Venusian atmosphere: 

about twenty molecules per billion located 

kilometers above the planet’s surface in its 

thick clouds. And since phosphine breaks 

down under the conditions of 

the Venusian atmosphere, 

the team calculated that 

a constant influx of 

new phosphine into the 

atmosphere would 

be necessary for 

them to detect this. 

Data in hand, 

Greaves and her 

colleagues had quite the 

paper to write. They 

had to explain to the 

scientific community 

that they had detected 

something that was 

either at odds with our modern knowledge 

of chemistry or evidence of alien life. In 

September 2020, they published their paper 

in the journal Nature Astronomy. In a press 

briefing for the Royal Astronomical Society, 

Greaves and three of her coauthors presented 

slides that cautiously broke their news. One 

slide reads, “We are claiming that we have 

detected phosphine gas whose existence is a 

mystery: either new chemistry or possibly life 

production.” News outlets boasted headlines 

about the possibility of life on Venus, 

gently noting the possibility of unknown 

chemistry. But then in July 2021 came a 

shock. In the same journal, a different 

group of researchers responded with their 

own paper, brutally blunt in its title: “No 

evidence of phosphine in the atmosphere of 

Venus from independent analyses.” 


Astronomy 

FEATURE 

“It felt pretty bad, on a 

personal level,” Greaves 

said in a recent 

interview, reflecting 

on the scientific 

controversy that 

followed the response 

paper. The response 

paper shrouded their 

original publication 

in questions of scientific 

validity and academic rigor. 

“There was anxiety, in case we 

had made a genuine mistake—but the 

critics had not involved us in any collegial 

discussion before publishing their critique,” 

Greaves said. 

The response paper opposed the original 

work on several fronts. First, the authors 

pointed out that the staff at ALMA had 

made an obscure but impactful mistake 

in their own data processing procedure 

before passing the data on to Greaves and 

her colleagues for their analyses. This 

mistake was corrected, as were two other 

small mistakes that the telescope staff 

discovered following an investigation, but 

it was not a fatal blow to Greaves’ paper— 

the signal was still there after adjusting 

the data. The bigger problem was that 

the response paper made the dramatic 

accusation of data misinterpretation. The 

signal, these authors claimed, came from a 

contaminant, not phosphine. 

The distinct frequency of radiation that 

phosphine absorbs—the missing frequency in 

radiation from the atmosphere of Venus that 

alerted Greaves to phosphine’s presence—is 

close to the frequency associated with sulfur 

dioxide. Through their own calculations and 

analyses, the authors of the response paper 

argued that the signal Greaves picked up on 

was actually from sulfur dioxide. 

But wait!—Greaves and her colleagues 

said in a third paper published in the 

same journal. Greaves’ team had already 

considered this kind of contamination and 

ruled it out. “We looked at the criticisms and 

found (in most cases) the critics hadn’t read 

the long supplement to our discovery paper, 

where we had already tested and answered 

the things they thought we’d done wrong,” 

Greaves said. The group reiterated their point 

from the first 

paper—there 

is indeed 

p h o s p h i n e 

on Venus—and they 

recalculated their 

estimates for the 

concentration of 

phosphine based on 

the now-corrected 

ALMA data. Even after 

the revisions, it remains 

possible that phosphine is 

being actively generated on 

Venus by some as-of-yet unknown 

mechanism. “I’d love it to be life, but other 

origins would be cool too,” Greaves said of 

the updated findings. 

Greaves noted that the scrutiny 

surrounding her group’s work extended 

beyond just the response paper published in 

2021. Some astronomers are still skeptical 

of the presence of phosphine on Venus in 

the absence of new data. But telescope time 

is tightly managed, so no one has been able 

to search for phosphine signals from Venus 

since the team’s ALMA observation. 

Greaves also highlighted the personal 

side of academic vitriol. “I still encounter 

problems, as does almost every woman 

astronomer I speak with,” Greaves said. “In 

the Venus case, it’s very clear that Anita [M. 

S. Richards] and I were the data analysts on 

the paper, and very clear also that people 

thought we must have made the most basic 

errors. It’s hard to see how that can be—given 

a quick search would have shown that we are 

both senior career stage and former staff at 

the telescopes we used for Venus—unless it 

was easy to assume women are incompetent.” 

The meaning of the phosphine detected on 

Venus is beyond what scientists can currently 

explain. When pushing the boundaries of 

knowledge, science requires a high degree 

of caution—after all, it took Newton two 

decades to publish his work on the theory of 

universal gravitation. So when answering the 

trickiest questions, equal parts skepticism 

and humility are required. We still don’t 

know what’s going on in the clouds of Venus, 

but it’s worth sincerely endeavoring to 

figure it out. ■ 



FEATURE 

Physics 

ROOM TEMPERATURE 

SUPERCONDUCTORS? 

NOT SO FAST 

BY YAMATO TAKABE & YOSSI MOFF 

The world of “Back to the Future,” 

where levitating hoverboards 

and cars are the norm, might 

not be as distant as it appears, thanks 

to superconductors. That level of 

prevalence and accessibility, though, 

hinges upon the discovery of room 

temperature superconductors. Until now, 

superconductors have only been found at 

temperatures far below freezing point. But 

a few months ago, a potential breakthrough 

in the discovery of room temperature 

superconductors was made. Unfortunately, 

many scientists were skeptical. 

Superconductors transmit an electrical 

current through themselves without losing 

any energy; in other words, they have no 

electrical resistance. Additionally, unlike 

normal conductors, which allow magnetic 

fields to pass through, superconductors 

repel external magnetic fields—a property 

known as the Meissner Effect. This 

property allows superconducting materials 

to levitate in the presence of magnets: a 

macroscopic manifestation of quantum 

mechanical effects. 

With these powerful properties, 

superconductors have incredible 

applications. Room-temperature 

superconductors would allow for lossless 

electricity transmission over long 

distances. This could lead to a more efficient 

and cost-effective electricity distribution in 

the power grid. And this isn’t just a far-off 

future. Superconductors are already used 

in Magnetic Resonance Imaging (MRI) 

screening technology, which is widely used 

in the world of medicine. And the Maglev 

train, a levitating locomotive that can 

reach speeds of over 250 miles per hour, 

also relies on superconducting magnets to 

push it forward. 

However, these superconducting 

properties do not appear naturally. 

Superconductivity has only been 

observed when certain materials are held 

at extremely low temperatures, close to 

absolute zero (that’s 0 Kelvin, or -273°C). 

Ever since superconductivity was first 

discovered back in 1911 by physicist Heike 

Kamerlingh Onnes, scientists have tried 

to observe it at the highest temperatures 

possible. While improvements have been 

made, these materials must still be kept 


Physics 

FEATURE 

at extremely low temperatures to express 

their superconductivity. 

Unfortunately, maintaining low enough 

temperatures to trigger superconductivity 

is incredibly expensive. Superconductors 

are so useful that scientists are willing 

to pay large amounts of money in 

order to maintain their extremely 

cold environments. But what if this 

superconductivity could be triggered at 

a much higher temperature—say, room 

temperature? Techniques that were 

previously limited by exorbitant costs 

would then become widely available. 

Furthermore, the scientists who uncovered 

this secret would be catapulted to 

international fame with their Nobel-Prizecaliber 

achievement. 

Many scientists have spent years 

dreaming of this mission: to achieve 

superconductivity at room temperature 

and ambient, or standard, pressure." 

On October 2020, the first instance of a 

notable advancement in creating a room 

temperature superconductor was reported 

by a team led by Ranga Dias at the University 

of Rochester, and Ashkan Salamat at the 

University of Nevada. They claimed to 

have observed superconductivity in a 

material known as carbonaceous sulfur 

hydride (CSH) at 288K (15°C). However, 

this breakthrough came with a condition: 

it occurred within a diamond anvil cell 

under immense pressure—approximately 

1.5 million times Earth's atmospheric 

pressure. Additionally, there were many 

concerns raised about the processing and 

analysis of the data presented in the paper. 

In light of this, in September 2022, the 

journal Nature decided to retract the 

paper. Dias and Salamat claimed again 

in a second paper published in March 

2023 that they had discovered a room 

temperature superconductor, but this time 

with lutetium hydride and nitrogen added 

to the sulfur hydride. They asserted that 

it had the properties of a superconductor 

at temperatures of up to 294K (21°C) with 

much lower pressure. However, this paper 

was also retracted by Nature on November 

7, 2023, following similar concerns with 

their data. 

Sukbae Lee and Ji-Hoon Kim, both 

physicists from Seoul, South Korea, are 

yet another duo of scientists who claimed 

to have achieved this groundbreaking 

accomplishment. In late July, they 

published non-peer-reviewed pre-prints of 

their work, which is common for research 

scientists. At first glance, their findings 

were truly groundbreaking. They had 

discovered a material they named LK-99 

that demonstrated all superconductive 

properties under normal conditions, 

ostensibly achieving the world’s first roomtemperature 

superconductor. 

Researchers worldwide jumped onto 

this major breakthrough and tried to 

replicate it. Among the physicists who 

were reproducing and verifying the 

experiment was Yuan Li, a condensed 

matter theorist who leads a research 

lab at Peking University in China. Li 

collaborated with two other experimental 

physicists, providing interpretations of 

the measurements and observations. 

“At the beginning, it looked legit. The 

original authors, they do believe in what 

they are saying, and they are willing 

to disclose all the information to the 

scientific community so that everyone can, 

in principle, follow their steps and try to 

verify the observation,” Li said. 

Yet when Li and his team began 

repeating the experiments detailed in 

the original publication, their data did 

not support the original claim. Because 

the scientists claimed that LK-99 had 

superconductor properties at room 

temperature, the properties should have 

been easy to replicate. Yet many physicists 

and material scientists, including Li, 

struggled during their replication 

processes. When testing the levitation of 

LK-99, Li and his team observed that LK- 

99 didn’t fully repel the magnet. Instead, 

one corner of LK-99 touched the magnet, 

revealing that LK-99 was not levitating, 

but was still experiencing ordinary 

attraction to the magnet. 

Furthermore, they discovered that its 

resistance was not actually zero—a critical 

property of superconductors. With the 

evidence piling up against LK-99 being a 

room temperature superconductor, Li and 

his group published their findings in a 

scientific journal. It turned out that LK-99, 

at least at room temperature, was simply 

a semiconductor with ferromagnetic 

properties, or high susceptibility to 

magnetization.. Along with papers from 

other groups that also disproved the 

original claim about LK-99, Li’s paper 

helped relegate this highly-anticipated 

room temperature superconductor as one 

of science’s many failed attempts. 

“This brings light to the high stakes 

of popular science and the need for 

competent ‘referees’ to overlook the 

process,” Li said. Eye-catching research 

fields like superconductors could 

potentially revolutionize many industries, 

so there is naturally a lot more funding 

for these research projects, but also a lot 

more pressure to produce tangible results. 

More pressure for results means a greater 

likelihood of falsified, or in this case, 

prematurely published, research. Whether 

it comes from journal peer-reviewers or 

fellow scientists, regulation is needed to 

prevent misinformation or misconceptions 

from becoming mainstream science. 

Despite the failures, Li emphasized the 

importance of this research. “Although 

papers were rushed, we should still thank 

the researchers for their effort and bravery 

to produce the research. Any information 

is useful information, thus furthering the 

story,” Li said. 

In the quest to discover a room 

temperature superconductor, we 

are reminded to be transparent and 

skeptical. As Carl Sagan famously 

said, “Extraordinary claims require 

extraordinary evidence.” It is not a sign of 

failure to question extraordinary claims; 

rather, it is an essential element of the 

scientific process that ensures the integrity 

of scientific knowledge. So, while the 

journey to achieving room temperature 

superconductivity may still be ongoing, the 

Sagan Standard serves as a guiding light— 

reminding us to think boldly, but always 

demand extraordinary evidence in our 

relentless pursuit of scientific excellence. ■ 

ART BY 

KARA TAO 



SPECIAL 

Archives vs. Today 

From The Archives: Science Fiction 

Prediction of Scientific Fact 

Editor's Note: 

In the spirit of this special issue, we 

traveled back in time and dove into 

YSM’s archives, seeking to track how 

our perception of scientific progress 

has changed over the last century. 

We found one YSM article written by 

Yale physics major Henry Thwing in 

1951 (reproduced here), to which we 

asked one of our members to write 

a response (pg. 35). In this side-byside 

comparison, we examine how 

our vision of artificial intelligence 

(AI) technology—and how it is 

presented in literary science fiction— 

has changed between the midtwentieth 

century and the present. 

To most dyed-in-the-wool science fiction 

fans, any suggestion that science fiction 

may be utter nonsense is sacrilege. They 

will immediately point to Jules Verne, the first 

truly great science prophet. His submarine in 

“Twenty Thousand Leagues under the Sea”, 

written in 1870, has a design very similar to 

present day construction and is run by an 

electric motor and screw. The “Gymnote”, built 

in 1888 was the first submarine to incorporate 

this improvement. 

Now, in modern science fiction, the writers 

are attempting to predict what the world will 

be many years from now. Even among stories 

written in recent years, it is not difficult to find 

those which have come true. “Deadline” by 

Cleve Cartmill was so accurate in its description 

of an atomic bomb when it appeared in 1944 

that the author was investigated for connections 

with the Manhattan Project. It is just as likely 

that some of the stories being published today 

will become realities in the near future. 

Let us look into the various types of science 

fiction stories to see just how and what the 

author predicts. 

*** 

[One] field in which the author attempts 

a sincere prediction is that of robots. There 

is a very important question in connection 

with thinking machines which most of these 

stories consider: “If we build intelligent robots, 

will they become our masters?” The resultant 

answers vary. Usually there is a condition 

to all thinking the robots do which is built 

into their machinery—no harm must be 

done to any human being. Jack Williamson's 

“Humanoids” follow this directive in an odd 

way. They restrict the motions of humans so 

severely that life becomes a hell of inaction. 

Their actions are directed entirely by cold 

logic. Isaac Asimov, in his series, has equipped 

robots with the human emotion of a love 

somewhat like maternal love, overcoming 

this difficulty. Other emotions which have 

been granted robots by their authors are 

pride, respect, and even sexual love. A good 

example of the latter appeared in a November 

issue of Collier's under the title of “Epicac”, in 

which an electronic calculator falls in love 

with its female operator. In all these cases, 

the author is trying to see what will be the 

effect both on men and on the robots if the 

machines should have the qualities which 

he postulates. 

Modern electronic calculators merely carry 

out mathematical operations, introducing 

no new variables and no original thought. 

Even then, however, they exhibit properties 

sometimes with a striking similarity to mental 

aberration. If a calculator could be made which 

by HENRY W. THWING, 1951 

would correlate data in ways other than those 

fed into it, then it would be a thinking machine 

much as those stipulated by science fiction. 

Sociological development offers another 

field of prediction. Here, the writer observes the 

recent development in our customs, especially 

our growing dependence on science and 

machines and extrapolates into the future. To 

some, science will eventually yield a paradise 

on Earth; to others, the cold objectivity of 

science will fail to realize the importance of 

the individual and the result of science in 

the government (which both types of story 

predict) will be a stricter life even than that 

under a military government. Some authors 

even predict a world of neuters in which 

babies are developed by chemical processes. 

Although this seems unlikely, it is nevertheless 

an attempt to foretell the path along which our 

society will advance. 

*** 

Stories such as these offer food for thought. 

Scientists and engineers make up a good share 

of those who are avid fans of science fiction. 

The stories tell them what might be invented 

and then they frequently try to develop it. 

When it became necessary to develop a 

suitable dress for high-altitude flight, one 

of the adopted styles was a copy of science 

fiction’s space suit. In particular, the “goldfish 

bowl” helmet (which allows the pilot to look 

around without turning his whole body) was 

used. (Astounding Science Fiction, Vol. L, No. 

1, March 1948. “The Space Suit” by L. Sprague 

de Camp) 

One should not criticize the fantastic nature 

of science fiction before carefully considering 

the many consequences it has led to in 

modern science. The fantasy of other ages 

has continued to be the reality of the present. 

With an honest look at the history of scientific 

discovery, who can claim to deny the heuristic 

value of the wild ideas of fiction? Indeed, will 

it not continue to be true that the seeds of 

science fiction today will yield a harvest of 

new scientific discovery tomorrow? ■ 

34 Yale Scientific Magazine January 1951 (Reprint) www.yalescientific.org

Archives vs. Today SPECIAL 

When Science Fiction Becomes Fact 

Responding to The Rise of "Thinking Machines" 

by IAN GILL, 2023 

Will we one day live in a world 

dominated by thinking machines? 

This is the central question of 

Thwing's 1951 article in Vol. 25 No. 4 of the 

Yale Scientific (reprinted on pg. 34) and one 

that is often posed today. But perhaps a more 

pertinent question to ask is: do we already live 

in such a world? In his article, Thwing posits, 

“If a calculator could be made which would 

correlate data in ways other than those fed 

into it, then it would be a thinking machine 

much as those stipulated by science fiction.” 

According to his definition, thinking machines 

are already deeply integrated into our society, 

from the Tinder and Hinge algorithms that 

determine who we might fall in love with to 

programs used by financial firms that shape 

economic development across the globe. 

What captures our attention, and our fear, 

most about Thwing’s thinking machines is 

the possibility that they might be able to think 

autonomously. Most people would argue 

that social media algorithms and similar 

technologies don’t “control” our society in 

the way that past science fiction writers have 

described: they lack independence and only act 

on human command. But the possibility that 

machines could surpass this limit—an idea 

that in Thwing’s age was relegated to writers’ 

rooms and dinner party conversations—has 

become far less remote. With the advent of 

the language model-based chatbot ChatGPT, 

our society has had to grapple with artificial 

intelligence (AI) as a force capable of changing 

our entire way of life. 

Here at Yale, for instance, the Schmidt 

Program on Artificial Intelligence, Emerging 

Technologies, and National Power under the 

Jackson School of Global Affairs describes its 

aim as to “examine how AI has the potential to 

alter the fundamental building blocks of world 

order.” This is what the AI-related science 

fiction that Thwing describes aimed to do— 

only now, this task has moved from the realm 

of speculation to the realm of academic inquiry 

and policy development. In a poll of 119 CEOs 

conducted by Yale School of Management 

professor Jeffrey Sonnenfeld, over forty percent 

indicated that they believed that AI had the 

potential to destroy humanity in the next five 

to ten years. While these respondents may not 

be the most technically knowledgeable on AI, 

the fact is that their opinions will govern how 

we integrate AI into our everyday lives. 

Despite recent advances, some believe that 

human-like, emotional AI will remain in the 

realm of fiction. In an opinion piece published 

in The Washington Post in April, Yale professor 

of computer science David Gelernter argues 

that software is fundamentally unable to 

experience consciousness. He suggests that 

the concept of a conscious computer is akin 

to a conscious toaster. AI will never be able to 

“understand” the world as humans do—it will 

only be able to draw surface-level connections 

based on the data it receives. 

Whether or not you agree with Gelernter, 

the fact remains that AI will play an 

increasingly significant role in our society. In 

his article, Thwing says, “The seeds of scientific 

fiction today will yield a harvest of new 

scientific discovery tomorrow.” In this sense, 

his proposition is firmly validated. As for 

whether our technology will come to control 

us, I would argue that it always has, in the same 

way that we control it. Just as the invention of 

agriculture changed human social structures 

from small hunter-gatherer communities to 

larger sedentary settlements twelve thousand 

years ago, technological breakthroughs alter 

not only our ability to interact with the world, 

but also our core values as a species. Our 

values, in turn, mold how we employ and 

develop future technology. 

Thwing’s article is fundamentally about the 

value of science fiction, and thus any analysis of 

his work would be incomplete without asking 

what will become of science fiction in the 

world of AI. I would argue that it will remain in 

the same place that it’s always been in. Science 

fiction, and art in general, is not something 

that we produce for the sole purpose of mass 

consumption. Perhaps some science fiction 

novels of the future may be written by nonhuman 

authors, but this does not mean science 

fiction as a whole will become an automated 

process by which we will become “robotic” 

consumers. An AI-generated story might 

spark an idea for a different story written 

by a human author, which would in turn be 

incorporated into the AI database. 

Just as humans mutually benefit from 

sharing their literary works with one another, 

the same may hold true for humans and 

AI. Beyond the specific details of how this 

relationship might work, one thing remains 

clear: humans will always dream about the 

world of tomorrow, and as long as we do, 

science fiction will always have a place in our 

collective consciousness. ■ 

Image Generated by ChatGPT 



HISTORY OF HYPE AND FAILURE 

BY XIMENA LEYVA PERALTA 

SCIENCE 

IN 

IMAGE COURTESY OF FLICKR 

It is the late 1910s. Airship travel between German cities has just become a reality. 

Newspapers report that a trip across the Atlantic will soon take place. Airships 

seem to be the future of transportation. 

But during the following decades, airship accidents keep happening. In 1937, one 

explodes during its flight from Frankfurt to New Jersey. Thirty-five passengers are 

immediately killed, and the era of airship travel abruptly ends. 

In his book Invention and Innovation: A Brief History of Hype and Failure, 

Czech-Canadian policy analyst and scientist Vaclav Smil examines the failures that 

arise when a product or process fails to meet expectations. He first distinguishes 

between invention (creating new ideas and products) and innovation (introducing, 

adopting, and mastering inventions). “There could be plenty of invention without 

commensurate innovation,” he explains. In his book, Smil examines three categories 

of failures: “unfulfilled promises, disappointments, and eventual rejections.” 

The first category comprises inventions that were initially praised but were 

eventually viewed with widespread suspicion. One example that Smil cites is 

chlorofluorocarbons (CFCs), nonflammable hydrocarbons widely adopted as 

refrigerants in 1930. Fifty years later, it became clear that CFCs cause substantial 

damage to the ozone layer, and international measures were instituted to eliminate 

their use. A second example is dichlorodiphenyltrichloroethane (DDT). DDT was 

introduced as a powerful insecticide in the 1940s and successfully prevented five 

hundred million deaths due to malaria, but was eventually linked to adverse effects 

on the environment. However, its success in saving lives meant that DDT required 

more nuanced regulations. 

The second category consists of technical advances that the public immediately 

welcomed but that ultimately ended in disappointment. For instance, airships 

seemed like they would dominate air travel between the 1910s and 1930s, but their 

instability, coupled with the rapid development of airplanes, cut their lives short. 

Nuclear fission, the splitting of atoms, is a second example: in the 1970s, there was 

widespread scientific agreement about its success, and General Electric predicted 

the end of fossil-fueled energy generation by 1990. As of 2022, only ten percent of 

world energy is generated by nuclear reactors. 

The third category includes inventions that we keep waiting for. The first example 

Smil provides is travel in a near vacuum, called a hyperloop, whose origins trace 

back to the 1820s. However, as of 2023, there are no operating hyperloop lines. 

Another highly anticipated invention he lists is nuclear fusion, the combination 

of atomic nuclei. Thought to be the ultimate clean energy source, it is still far from 

commercial implementation. Smil notes that mass media has inaccurately labeled 

all fusion advancements as breakthroughs instead of proof-of-concept experiments. 

Although dense at times, Smil’s data-driven and articulate writing delivers sharp 

critical analyses of humankind’s greatest failures. He contrasts positive opinions 

about inventions with data supporting their negative repercussions. In the final 

chapter, Smil warns readers against the myth of ever-growing innovation. “Success 

is only one of the outcomes of our ceaseless quest for invention,” he says. Just as our 

past is plagued by disappointment, our future will inevitably be filled with scientific 

failures—some of which will hopefully, one day, lead to eventual success. ■ 

T 

S 


SERENDIPITOUS SCIENCE 

BY JAMIE SEU 

Oops! is not a word you want to hear in the lab. Unfortunately (or not), 

accidents are a common reality in research. But sometimes, these 

mistakes can bring about valuable revelations, as discovered by the 

nominees of NPR’s Golden Mole Award for Accidental Brilliance. 

A podcast presented by Skunk Bear, NPR’s science-centered YouTube channel, 

highlights five instances of serendipitous scientific discovery, including the 

story behind the winner of the Golden Mole, Elizabeth Tibbetts. A biologist at 

the University of Michigan, Tibbetts was researching wasp behavior when she 

stumbled upon a fascinating revelation: wasps can recognize each other’s faces, 

just as humans can. 

The realization started with a careless mistake. To study wasp behavior, Tibbetts 

taped and watched video footage of the insects, analyzing interactions between 

colony members. She color-coded each wasp with a dot of paint, a critical step that 

allowed her to distinguish between the insects. One day, however, she discovered 

that she had forgotten to paint a few wasps, leaving her with what she thought was 

a frustrating waste of a recording. But something caught her eye—she realized 

that the wasps had discernible facial features. “I could still tell them apart, just by 

their natural patterns,” Tibbetts said. Upon closer inspection, Tibbetts identified 

unique colors, patterns, and “eyebrow” structures that allowed her to differentiate 

them. The question then became: If she could distinguish between individuals, 

could the wasps themselves tell each other apart? 

THE 

According to prior research on insect behavior, the answer was no. But 

Tibbetts was determined to investigate the subject herself. “Maybe if I had more 

experience, I wouldn’t have pursued it, because maybe I would have thought it 

was implausible,” Tibbetts said. Fortunately, she pushed on and determined that, 

yes, wasps can recognize each other. Furthermore, it is this ability that facilitates 

complex social interactions between members of a colony and allows for wasps to 

develop personal relationships. 

Tibbetts’ serendipitous tale was one of hundreds of stories submitted to Skunk 

IMAGE COURTESY OF PIXABAY 

Bear. One notable runner-up was George Liu, a researcher at the University of 

California, San Diego, who discovered the novel use of pigment as a bacterial 

defense mechanism after his lab equipment was contaminated with bleach. Other 

memorable contenders included former Stanford University undergraduate Nate 

SPOTLIGHT 

Cira and his adviser, Manu Prakash, who discovered the role of evaporation and 

surface tension in artificial chemotaxis, the movement of a particle in response 

to a chemical stimulus. While these stories only offer a glimpse into the myriad 

of ways in which discoveries can be made, they highlight the value of mistakes 

in research. Skunk Bear’s Golden Mole Award takes a creative approach to 

emphasize this lesson, presenting the “what” and “how” of the research in an 

amusing manner. Any listener curious about the “why” will need to engage in 

some investigation of their own due to the podcast’s brevity. 

Skunk Bear’s Golden Mole segment is worth a listen for any person, researcher 

or not, who could use a reminder about the importance of adaptability and 

perseverance. If we can learn anything from these scientists, it’s that “oops” can 

be okay sometimes. It might even lead to something great. ■ 



COUNTERPOINT 

RECKONING WITH 

THE GHOSTS OF 

YSM’S PAST 

In 1903, Yale undergraduate Almer Mayo Newhall 

wrote on “The Position of the Negro within the 

Human Family.” The piece opens with a promise 

to inspect “what characterizes the inferiority of the 

Negro to the white man”—an “inferiority” which, by 

its final assertion, justifies that the North’s “slavery 

legislation was a failure.” The article appeared in Vol. 

IX No. VI of the Yale Scientific Monthly, the precursor 

to the Yale Scientific Magazine. 

Newhall’s piece is a damning, though hardly isolated, 

artifact within an extensive archive of racist scientific 

publishing at Yale and beyond. At the same time that 

the American Eugenics Society opened its headquarters 

on Hillhouse Avenue and North Carolina was enacting 

its first forced sterilization campaign in 1929, YSM 

was printing articles about “The Need of Immigration 

Restriction” and “extremely primitive, unpatriotic, 

seemingly indolent and childish … Africans of today.” 

On one hand, the insidious context deflects blame 

from the undergraduates writing for Yale Scientific 

Monthly at the time. Systemic racism in the United 

States did not originate with scientific journalism, 

which reflects scientific research, which reflects public 

discourse. But publishing is not a passive process either. 

What gets published directly shapes public discourse, 

future research, and the policies that govern our social 

structures. And so scientific communication, if done 

poorly, reproduces harm and injustice. 

So, where did Newhall go wrong? For one, it’s bad 

science. He predicates neural behavior on phrenology, 

the shape of one’s skull. He employs dubious-at-best 

methodologies, claiming that the “trained eye” can 

detect more convolutions in the white man’s brain. He 

uses evidence that is simply false, arguing, at one point, 

that Black people have pharyngeal pouches that white 

people lack. And he invents fictitious history when his 

evidence fails, imagining “the Negro in his own native 

jungle,” brought into “contact with civilization” by 

Europeans. Not to mention that the “white man and 

the Negro” is fundamentally a false dichotomy, which 

dooms the entire article’s logic before it begins. 

Newhall’s article should have never been approved for 

publication in a scientific magazine. But the conversation 

shouldn’t revolve around whether Newhall’s article used 

faulty induction (it did), or whether race science is a 

legitimate science (it’s not). The conversation should 

revolve around whether certain research queries, 

BY SAMANTHA LIU 

IMAGE COURTESY OF PIXABAY 

however rigorous, are simply morally bad questions. This 

is where the editorial role of a public-facing magazine 

like the Yale Scientific bears a different responsibility 

than a reviewer for an academic journal like Nature. 

As journalists first, and scientists second, we should 

recognize that “science for the sake of science” is never 

enough, because science never exists in a vacuum. 

The demand to simply have more moral sense gets lost 

among structures of Eurocentrism and exclusion which 

govern scientific communication. In journalism—a field 

that already favors the white and wealthy—scientific 

coverage is among the least diverse. According to the latest 

Pew Research Center report, only three percent of media 

journalists covering science and technology identify as 

Black, compared to the nationwide six percent. And for 

members of the National Association of Science Writers, 

in 2021, only one percent identified as Black. 

Beyond diversity at the editorial level, scientific 

communication is—and will remain—inaccessible if it 

limits itself to what gets published in leading research 

journals. A paper costs thousands of dollars to publish, 

and research itself is getting costlier. Such economic 

barriers are compounded for Black and women 

scientists, who are less likely to receive grants from the 

National Institutes of Health. While it’s easier to source 

stories from the front pages of Nature, these findings 

originate from scientists who benefit by affiliation with 

well-endowed institutions. Meanwhile, on a global scale, 

the landscape of publishing marginalizes non-Western 

scholarship, stereotypically deemed “unscientific.” While 

there is invaluable knowledge possessed by indigenous 

populations about environmental sustainability, or 

by scientists in the global South on tropical diseases, 

they never receive the limelight of research journals. 

Here, scientific magazine boards have the capacity to 

recognize—and rectify—the inequities that arise at 

the level of academic publishing by broadening who is 

credited as an “expert.” 

While DEI (diversity, equity, and inclusion) is often 

demeaned as a corporate buzzword, diversifying these 

stories matters. Scientific journalism is the link between 

academic research and public perception—and in 

the scientific world, attention is currency. What gets 

published goes on to influence what research gets funded 

in the future. By being deliberate about these choices, the 

Yale Scientific Magazine can reach beyond the confines of 

its past, working toward a safer and fairer future. ■ 


I 

read an article from a 1956 issue (Vol. 30 No. 8) 

of the Yale Scientific Magazine titled “Teflon Resin: 

Preparation and Characteristics,” further discussed 

in this issue on pg. 19. The article mostly describes how 

Teflon—a DuPont brand name for a resin made from 

polymerizing tetrafluoroethylene—was first produced. 

The Teflon polymer was originally discovered when a 

DuPont scientist noticed that it appeared in a powdery 

form when tetrafluoroethylene monomers were stored 

at super-atmospheric pressures. The article goes on 

to describe Teflon’s unique properties, the modern, 

efficient manufacturing process, and the “brilliant 

future” that the compound holds. I found it ironic and 

somewhat depressing to read this article—which was 

full of excitement for the chemical—from a modern 

perspective, knowing how damaging Teflon and other 

similar plastics have been to the environment. 

I wanted to reimagine the discovery and production 

of Teflon from the perspective of the molecules 

used to make it. If they could think, how might 

these molecules, which once made up the bodies of 

living creatures before decomposing into oil, feel 

about being dredged up from the ocean? Humanity’s 

overconsumption and production of plastics disrupt 

Earth’s natural cycles of renewal, in which the 

biological decays, but remains natural. Once extracted 

from the earth, the compounds used to make Teflon 

PERI 

A NEW PRECIPITATION 

Artist’s Statement 

Into the earth the oil well dips like a crane, dredging up 

Slick-oils, sucking, gulping from the seafloor ancient crud 

& festering remains of our ancestors: the turnover, the dredge, 

Forgotten by all but time & rock & rot. Into the light they rain 

Upwards, unwilling, compounds of bodies torn from dark sleep, 

Filling test tubes, measured by blasts of radioactive sulfur. Cut up 

& compartmentalized, monomers polymerized, fumigated under an 

Indoor sky, inhaling the spiky scent of fluorine. The reactive turns inert, 

Carbon dead-eyed behind a veil of single bonds. Molecules forget the pull 

Toward entropy. They will never be bones again. They are stuck always in 

Non-life, imitation bone—teflon—ugly name, ugly destiny, smooth vacuum 

Of un-possibilities. Made here & there, again & again, more spilling out, fragmenting, 

sifting into soil & water & bodies of fish & floating islands of plastic, 

Until they gloss over the entire earth—slick, smooth, white. Almost like snow. 

experience all sorts of unnatural transformations, 

which I tried to evoke in my poem. For example, 

“radioactive sulfur” is a reference to the process used by 

the researchers to estimate Teflon’s molecular weight, 

and “fumigated under an indoor sky” represents the 

way the monomers are polymerized under intense 

pressure. The veil of fluorine is a response to one of 

the qualities of Teflon that the original article was so 

excited about: because the compound is essentially a 

string of carbons all single-bonded to fluorine, and 

C-F bonds are extremely strong, Teflon is remarkably 

inert, both chemically and physically. How might 

carbon molecules, which are used to interacting with 

the world through biological reactions, feel about 

being cut off from the world by these C-F bonds? 

Finally, I wanted to move beyond the scope of 

the original article to discuss the overproduction 

of Teflon and other plastics. The overproduction of 

plastic contributes to global warming, and plastic itself 

inevitably leaks into and pollutes the environment. 

I made my lines progressively longer, so the poem 

itself spills outward. In an age where more and more 

of the environment has been affected by humans— 

with pollution and global warming changing even the 

atmosphere and weather patterns—are we dooming 

ourselves to a world where artificial wonders such as 

Teflon replace natural ones? ■ 

METER 

BY MOLLY HILL 

ART BY KARA TAO 



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YSM Issue 96.4

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