YSM Issue 89.2

Yale Scientific 

Established in 1894 

THE NATION’S OLDEST COLLEGE SCIENCE PUBLICATION 

MARCH 2016 VOL. 89 NO. 2 

TO 

IMMUNITY 

ANDBEYOND

q a 

& 

►BY CLIO BYRNE-GUDDING 

Have you ever tried to count the stars? 

As a kid, you probably relied on your index 

finger and a good eye, but our universe 

extends far beyond the visible night 

sky. 

Since it is impossible to count all existing 

stars individually, astronomers use 

galaxies to approximate a number. Stars 

usually form in clusters within galaxies, 

from large clouds of gas. “Galaxies can be 

used as representational volumes,” said 

Robert Zinn, an Astronomy professor at 

Yale. “In our galaxy, there are something 

like 100 billion stars.” By multiplying the 

numbers of stars in our galaxy by the approximate 

number of galaxies in the universe, 

astronomers estimate that there are 

roughly 10 22 stars in the universe. 

However, this approximation is likely 

inaccurate because all galaxies are different. 

To produce better estimates, astron- 

How Many Stars Are There in the Universe? 

IMAGE COURTESY OF WIKIMEDIA COMMONS 

►The Andromeda Galaxy, as captured by 

a telescope. The red represents infrared images, 

while the blue represents X-ray images. 

omers use powerful telescopes to determine 

the luminosities of galaxies and 

rates of star formation. 

As our imaging capabilities improve, 

so do our estimates. In 1995, the Hubble 

Space Telescope produced a deep field 

image indicating that star formation had 

peaked several thousand million years 

ago, but astronomers now say that dust 

clouds blocked many stars in the old image. 

With infrared, modern telescopes 

could reveal these hidden stars. The Gaia 

Space Observatory, for instance, is currently 

tracking approximately one billion 

stars within our galaxy, improving 

our understanding of stellar properties 

and the universe at large. 

So, when you look up at the night 

sky, remember that you are only seeing 

a small fraction of the stars within 

the universe. 

How Do You Explain the Winter that Wasn’t? 

►BY ARVIN ANOOP 

If you are celebrating the warmer temperatures 

and uncharacteristic winters, 

thank El Niño. If you’re complaining about 

the cancellation of your skiing and snow 

tubing trips, blame El Niño. The force behind 

the odd weather, El Niño is an aberration 

of ocean currents that affects atmospheric 

patterns, causing unexpected 

climatic changes. 

As you might notice at the beach, the 

world’s ocean waters are in constant motion. 

In fact, they follow systematic, predictable 

trajectories in the form of currents, 

which are caused by wind forces and differences 

in water density at different locations. 

Normally, ocean currents in the Pacific 

Ocean carry warm water from the west 

coast of Latin America towards Australia 

and Southeast Asia. These currents are 

driven by trade winds — a pattern of surface 

winds that follow constant trajectories 


►On the east coast, flowers could be seen 

blooming in December. 

— and they make the Asian and Australian 

side warmer and wetter while keeping the 

Latin American side cooler and drier. 

During El Niño years, trade winds weaken, 

and the warm water accumulated near 

Southeast Asia and Australia swamps 

east. The Latin American and Californian 

coasts become wetter and warmer. 

Around the world, El Niño has been associated 

with dry forest fires in Indonesia, 

droughts in southern Africa, mitigation of 

the Indian monsoon, and flooding in the 

tropics. 

The 2015 El Niño is arguably the strongest 

recorded in human history, and although 

it is a natural phenomenon, the 

science behind it is not completely clear. 

Thus, the recent increased frequency of 

Super El Niño events and their possible 

association with global warming have become 

the basis for future research.

Yale Scientific Magazine 

VOL. 89 ISSUE NO. 2 

CONTENTS 

MARCH 2016 

NEWS 5 

FEATURES 25 

ON THE COVER 

20 

TO IMMUNITY AND 

BEYOND 

As we age, so does our immune 

system. But one hormone could 

help rejuvenate the body’s defenses, 

Yale researchers report. 

12 

THE FLOW 

OF FLAVOR 

We smell our food only when we 

exhale. Here’s why it matters. 

14 

WHAT MAKES US 

GENEROUS 

Neuroscientists, curious about 

what generosity looks like in the 

brain, tell a story of how emotional 

processing and mirror neurons encourage 

social behavior. 

17 

IS TIME RUNNING 

OUT? 

Are we living through a sixth mass 

extinction? Maybe not, and in fact 

perhaps we should start looking 

beyond species extinction. 

23 

SUNSCREEN BLOCKS 

MORE THAN SUN 

Ordinary sunblock sinks into the skin, 

diminishing its protective properties. 

Yale researchers now have a new 

sunblock formula. 

More articles available online at www.yalescientific.org 

March 2016 


3

FEATURE 

cartoon 

GRAVITATIONAL WAVES 

►BY DELEINE LEE 

DORKUPINE COMICS 

advertisement 

The Economy Doesn’t 

Affect Our Quality.

F R O M T H E E D I T O R 

The new year opened with a bang. Or, more precisely, it opened with a chirp, 

as physicists finally picked up the gravitational waves that Einstein predicted a 

century ago. Scientists have called it the biggest discovery of the century. We 

think the year has barely begun. 

Last March, we heralded the rebirth of Wright Laboratory, when Yale’s particle 

accelerator made way for new facilities dedicated to the study of dark matter and 

neutrinos—tiny particles that zip through the universe near the speed of light. 

One year on, Wright’s transformation is well under way. Wright Lab research has 

turned our understanding of neutrinos on its head (pg. 11) and, along with work 

at Fermilab and other institutions around the world (pg. 6), promises to change 

how we conceive the cosmos. 

From rethinking our fixation on species extinction as an indicator of our biosphere’s 

health (pg. 17) to repurposing small cellular vesicles to deliver drugs 

to cancer cells more effectively (pg. 28), the story of science is one of ongoing 

innovation and change. Our cover story (pg. 20) features an exciting finding in 

immunotherapy, a field that has seen a wave of breakthroughs as scientists bring 

our most powerful tools to bear in pursuit of an elegant idea: giving our body’s 

immune cells—already honed over millennia of evolution—the edge they need 

to win the arms race against cancer and pathogens. 

Science can be intimidating. It is easy to talk about the upcoming presidential 

elections and much more difficult to discuss recent advances in genetic engineering. 

But as scientific innovation reshapes our world and poses fundamental 

questions about what it means to be human, we at Yale Scientific truly believe 

that all of us need to get comfortable—very comfortable—with science. And we 

are excited to embark on this mission, making science friendly and accessible to 

readers who have long since forgotten the teachings of their high school chemistry 

teachers. In these pages, we hope that once-abtruse concepts grow into 

familiar friends and that you rediscover the joy and awe of scientific discovery. 

In the words of NIH Director Francis Collins (pg. 37), there’s a huge frontier 

out there for us to conquer. And we will need not just the ingenuity of our scientists 

but also the vision of our policymakers and the support of our citizens 

to get there. 

Happy reading, and here’s to an exciting year. 

A B O U T T H E A R T 

Lionel Jin 

Editor-in-Chief 

The cover, designed by arts editor Ashlyn Oakes, depicts 

the artist’s interpretation of the protection conferred by a 

hormone produced in the thymus, a small gland nestled 

between the chest bone and heart. In the foreground, a 

protective T cell barrier shields the silhouette of an elderly 

woman from the grasping hands of the Grim Reaper, or 

perhaps the Fates of Greek Mythology. T cells are nursed 

to maturation in the thymus and Yale researchers now 

know Fibroblast Growth Factor 21 to play an important 

role in reducing age-related thymus degeneration, giving 

our immune systems a welcome boost. 

Editor-in-Chief 

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NEWS 

in brief 

Fermilab & the Future of High Energy Physics in Yale Hands 

By Colleen Coffey 


►A view of Fermilab from above. Yale 

physics professor Bonnie Fleming was 

recently appointed Deputy Chief Research 

Officer at Fermilab. 

Starting in 2016, Yale Physics Professor 

Bonnie Fleming will split her time between 

Yale and Batavia, Illinois, where she will 

oversee the booster accelerator neutrino 

program and the Deep Underground 

Neutrino Experiment (DUNE). These two 

neutrino research programs take place at 

Fermilab, a Department of Energy laboratory 

that conducts basic research in particle 

physics. This field could revolutionize the 

way we look at the universe. 

Professor Fleming started her research 

at Fermilab as a graduate student and 

will continue her research now as Deputy 

Chief Research Officer. DUNE investigates 

the properties of neutrinos, elementary 

particles produced by radioactive decay. The 

project will look for differences in neutrino 

and anti-neutrino oscillations—changes in 

the neutrinos as they move through space. 

These could provide clues to why we live in a 

universe largely composed of matter, rather 

than in one containing equal parts matter 

and anti-matter—matter’s oppositelycharged 

counterpart. 

“When we create matter and anti-matter 

in the laboratory we can only do so in 

equal amounts,” Fleming said. “In the 

early universe there must have been some 

imbalance in their creation, leaving us with 

a matter-dominated universe,” she added. 

DUNE will use a neutrino beam produced 

at Fermilab and directed to a Liquid 

Argon Time Projection Chamber Detector, 

a particle detector situated in an old 

underground gold mine. As Deputy Chief 

Research Officer, Professor Fleming will be 

responsible for networking with Congress, 

the Department of Energy, the National 

Science Foundation, and the broader 

community, as well as continuing her 

research at the lab. The research she oversees 

could greatly improve our understanding of 

the universe itself. 

Funding the Fight against Typhoid Fever 

By Dawn Chen 

IMAGE COURTESY OF VIRGINIA PITZER 

►A shed toilet found near the river in 

Fiji. Although there is sufficient fresh 

water on the planet for everyone, millions 

still die from disease due to poor 

sanitation and lack of clean water. 

In Fiji, some toilets are built on riverbanks, 

allowing fecal matter to pass directly into 

nearby rivers where locals obtain drinking 

water. This creates the perfect breeding ground 

for waterborne diseases like typhoid fever. 

With the help of a $609,150 grant from the 

Bill & Melinda Gates Foundation, Yale School 

of Public Health professor Virginia Pitzer will 

develop statistical and mathematical models 

to estimate the cost-effectiveness of a new 

typhoid vaccine in countries like Fiji. 

Typhoid is caused by the bacterium 

Salmonella typhi, which is typically transmitted 

through contaminated drinking water. 

Causing up to 270,000 deaths per year, typhoid 

can lead to symptoms including high fever and 

abdominal pain. Though chlorination and 

filtration of drinking water can greatly reduce 

its incidence, over 21 million people still suffer 

from typhoid yearly due to poor sanitation. 

Current typhoid vaccines use the typhoid 

Vi antigen, triggering the immune system to 

produce antibodies. However, these vaccines 

are only effective for three to five years. A 

longer-lasting Vi-conjugate vaccine is in 

development. It combines the typhoid Vi 

antigen with another antigen, stimulating a 

stronger immune response. The Vi-conjugate 

vaccine can also be safely administered to 

infants, unlike current vaccines that cannot 

induce protective levels of antibodies in young 

children. 

Her models will account for both direct 

protection from the disease for vaccinated 

individuals as well as indirect protection from 

the decreased transmission of typhoid. “These 

models can allow us to explore how best to use 

these new vaccines in developing countries,” 

Pitzer said. “It will be useful for informing 

policies when the vaccines become available.” 

6 Yale Scientific Magazine March 2016 www.yalescientific.org

in brief 

NEWS 

Khushi Baby: Vaccination Records on a Necklace 

By Nishant Jain 

In 2014, Ruchit Nagar YC’15, YSPH’16 

began working on a project for his 

mechanical engineering class, Appropriate 

Technology and the Developing World, a 

project that would eventually evolve into 

the Khushi Baby system. Khushi Baby’s 

technology stores vaccination records on 

an inexpensive computer chip that can be 

worn in a necklace and later scanned by 

health workers with a mobile phone—all 

without Internet access. This is especially 

effective for rural regions in India with 

limited connectivity to a centralized health 

database. 

The Khushi Baby team did extensive 

research on Indian cultural norms to 

develop a system their target populations 

would use. Following tests of several 

wearable forms for the device, including 

a bracelet, they chose the necklace after 

noticing a common tradition in India for 

children to wear protective necklaces. 

“We paid a lot of attention to the 

[community] and how to generate demand, 

awareness, and trust. Even something as 

simple as picking the right form factor can 

have an impact,” Nagar said. 

The team has received support from 

several sources, including the Thorne Prize, 

Kickstarter, and the UNICEF Wearables for 

Good Challenge. Field tests in Rajasthan 

have yielded positive feedback, and more 

research studies are scheduled for the 

upcoming year. 

Nagar emphasizes that the key to Khushi 

Baby’s success is its attentiveness to cultural 

norms in the target population. “It’s not 

just about data capture. It’s not just about 

identifying the patient…it’s also about 

engaging the community and generating 

the demand [for the system]. And if we can 

attack all of those things with one project, 

then we have something that is different 

and worthwhile.” 

IMAGE COURTESY OF RUCHIT NAGAR 

►An infant wearing the Khushi Baby 

necklace. The form factor takes into 

account cultural norms in rural India to 

create a system more likely to be used 

by the target population. 

Plants in Arms: Chemical Defenses of Cress Plants 

By Valentina Guerrero 

Though we have long known that plants are 

vital to maintaining good health and preventing 

diseases, only recently have scientists begun to 

uncover the mystery and promise lying within 

their leafy tendrils. Yale professor Nicole Clay 

and her team of researchers, in collaboration 

with Stanford scientists, have discovered that 

plant defense compounds likely do more than 

just monitor antibiotic activity. These molecules 

also function as secondary messengers to 

regulate chemical signaling pathways and 

antibiotic activity. 

A recent Nature article featured the Clay 

Lab’s research identifying a cyanogen, or 

cyanide-releasing compound, involved in 

Arabidopsis metabolism called 4-OH-ICN. 

Both signaling and antibiotic classes of 

products were thought not to exist in the same 

plant species. Cyanogens are extremely rare in 

nature, so the researchers decided to further 

investigate the synthetic pathway leading to 

this particular molecule. They later found that 

mutating the enzymes involved in this pathway 

made Arabidopsis more susceptible to bacteria, 

implying that 4-OH-ICN is important in the 

plant defense response against pathogens. 

Some plant signaling pathways regulate 

signaling processes that are conserved between 

plants and animals. Thus, plant natural 

products are being investigated as effective 

anti-cancer agents and to assist in treating both 

human and plant diseases. 

“Plants are the world’s best chemists, and 

their natural products hold the key to the 

development of novel human medicines,” Clay 

said. Though there is still much work to be 

done to uncover the mysteries behind plant 

defense pathways, this research will surely 

lead to important advances for medicine and 

mankind. 


►Arabidopsis thaliana, commonly 

known as mouse-ear cress, can be infected 

with mildew and other diseases, 

making it important to understand the 

plant defense pathway. 

www.yalescientific.org 

March 2016 


7

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NEWS 

microbiology 

icamycin 

ion of Wall 

cid Synthesis 

S. aureus 

Antibody 

Recruitment 

TEARING DOWN A BACTERIAL BLOCKADE 

Applying chemical techniques to solve biological dilemmas 

►BY MILANA BOCHKUR DRATVER 

Bacteria are double-edged swords. Some microbes are 

necessary for healthy biological functioning. Others, 

such as Staphylococcus aureus, can evade the body’s immune 

response, grow out of control, and cause serious 

disease. A new discovery from the Spiegel Laboratory in 

the Yale Chemistry Department elucidates the potential 

mechanism by which S. aureus hides from the body’s defenses. 

Multi-drug resistant bacteria pose a serious public 

health threat because they are not easily killed by common 

antibiotics. Notably, certain strains of antibiotic 

resistant S. aureus have been responsible for the MRSA 

outbreaks that have plagued public health authorities. 

Yale physician-scientist Samir Gautam was one of many 

who wondered why conventional antibodies are ineffective 

at killing S. aureus. He was working as a postdoctoral 

research in organic chemistry, and he wanted to develop 

a vaccine against S. aureus. Then, he came across some 

electron micrographs of S. aureus published in the 1980s. 

“When we saw the scanning electron micrographs of the 

staphylococcal cell envelope covered with the hair-like 

wall teichoic acids, it struck us that these may be the reason,” 

Gautam said. 

Wall teichoic acids are long chains of sugar molecules 

that are covalently bound to the peptidoglycan cell wall 

of Gram-positive bacteria like S. aureus. Peptidoglycans, 

mesh-like structures composed of sugars and peptides, 

provide shape to bacteria. In S. aureus wall teichoic acids 

are known to contribute to infection and shield the bacteria 

from environmental threats. Based on this shielding 

function, scientists hypothesized that the wall teichoic 

acids could act as an immunological cloak, preventing 

conventional antibodies from recognizing and attacking 

the bacteria. Because the peptidoglycan cell wall is common 

to many species of bacteria, such antibodies could 

provide broad protection against S. aureus and other 

bacteria. 

Since commercially available antibodies for the bacterial 

cell wall are not specific enough to only target peptidoglycan, 

the lab decided to fix a chemical antigen in 

the cell wall. This would allow antibodies designed to 

recognize these chemical tags to bind with great affinity. 

To accomplish their goal, the researchers took advantage 

of a particular enzyme involving cell wall synthesis, successfully 

labeling the cell wall without disturbing its assembly 

or adversely affecting its integrity. The scientists 

then assessed the recruitment of a highly specific antibody 

to this foreign epitope, and they found that they 

were indeed able to engineer the specificity they needed 

using the chemical tags. 

Gautam applied this technique to the question of how 

and why S. aureus is able to survive attack by antibodies. 

The study found that antibody binding to the cell wall 

was blocked in the presence of teichoic acids but successful 

when the bacteria was stripped of this protective 

coating. These findings indicated to Gautam that teichoic 

acids play an important role in shielding the bacteria 

from the immune system. 

“The study exemplifies the power of adopting a 

cross-disciplinary approach to basic biology research,” 

Gautam said. Techniques in chemistry and synthetic biology 

were critical to the team’s work, and the combination 

of multiple armories from across different fields 

promises to bolster the search for solutions to some of 

the most pressing scientific problems. 

“This work offers new insights into the function of wall 

teichoic acids and the mechanisms this important human 

pathogen uses to evade the human immune system,” 

Gautam said. The findings provide a promising starting 

point for the development of better drugs and vaccines 

against antibiotic resistant bacteria. 

IMAGE COURTESY OF DAVID SPIEGEL 

►David Spiegel, a professor of chemistry at Yale University, 

recently discovered wall teichoic acids on S. aureus. 


environmental science 

NEWS 

FRICK’N FRACK’N 

Toxins from hydraulic fracturing raise health concerns 

►BY HOLT SAKAI 

PHOTO BY ELISE ELLIOTT 

►The researchers visited an area in Ohio with active hydraulic 

fracturing. This hydraulic fracturing site contains a central 

drilling derrick surrounded by several acres of cleared land to 

house supporting equipment. 

According to one theory, the temple of the Oracle of Delphi, 

an ancient Greek priestess, was located above an ancient natural 

gas spring. Geochemical analyses suggest that the Oracle would 

inhale natural gas and enter a trance-like state as she delivered 

her prophecies. 

Modern uses of natural gas have progressed significantly since 

the days of the ancient Greeks. Today, natural gas is second only 

to coal with regards to energy production in the United States. 

Advances in two key technologies—directional drilling and hydraulic 

fracturing—have driven the growth of the natural gas 

industry in recent years. Directional drilling involves digging 

non-vertical or even curved wells to access obstructed deposits, 

while hydraulic fracturing, commonly known as fracking, 

drives high-pressure fluids through these wells to fracture the 

surrounding rock. 

Over the last decade, new applications of these methods have 

led to a substantial rise in the domestic production of natural gas: 

from effectively nothing in 2000 to over 10 billion cubic feet per 

day in 2010. Production is projected to quadruple by 2040. This 

unchecked growth has been met with increasing concerns over 

associated environmental and human health risks. 

In a January 2016 paper, a research team led by Yale School 

of Public Health professor Nicole Deziel investigated over 1,000 

chemicals associated with hydraulic fracturing. Although they 

found little to no toxicity information for nearly three-quarters 

of the evaluated substances, the team discovered that many were 

linked with adverse reproductive and developmental effects. 

In hydraulic fracturing, millions of gallons of fracturing fluids—a 

mixture of water, chemicals, and sand—are injected into 

deep underground wells at high pressures, producing fractures 

in the nearby rock that release natural gas. The injected fluids, 

along with a potentially harmful mixture of displaced, naturally 

occurring chemicals, gradually return to the surface as wastewater. 

Though the wastewater is carefully collected for disposal, 

surface water and groundwater contamination from equipment 

failure or underground seepage remains possible. 

Furthermore, despite the procedural safeguards against contamination, 

official regulation at the federal level is surprisingly 

low. Under the Energy Policy Act of 2005, hydraulic fracturing 

chemicals were largely exempt from complying with the Safe 

Drinking Water Act’s Underground Injection Control Program, 

which establishes requirements to ensure the integrity of underground 

drinking water sources. 

With limited federal oversight, a combination of environmental 

and health concerns has led to the emergence of a vigorous 

anti-fracking movement. Still, proponents of unconventional 

natural gas argue that it is an inexpensive alternative to other fuels 

such as coal and oil, which are linked to higher levels of air 

pollution. 

Attempting to address the debate over fracking, Yale researchers 

systematically checked 1,021 chemicals—including heavy 

metals, organic solvents, and naturally-occurring radioactive 

materials—against an online database maintained by the Reproductive 

Toxicology Center. Of the 240 chemicals that possessed 

sufficient toxicity information, 157 were identified as possible reproductive 

or developmental toxins. 

Their analysis is a crucial first step toward understanding the 

impact of hydraulic fracturing on public health, particularly 

within communities situated near fracking sites. In the last year, 

over 8.6 million people in the US used a drinking water source 

located within one mile of a hydraulic fracturing site. 

As part of their findings, researchers also recommended 67 

chemicals as the focus of future health studies on hydraulic fracturing. 

Because these prioritized substances have either current 

or forthcoming quantitative standards, they represent the most 

sensible starting point for future human exposure assessments. 

“This was a systematic evaluation to prioritize these chemicals 

and get a better handle on their potential health effects,” Deziel 

said. 

By narrowing down the extensive list of chemicals to a few of 

particular interest, the research has also laid the groundwork for 

more focused and effective environmental testing. “We’re planning 

on collecting water samples to evaluate whether proximity 

to hydraulic fracturing activities is associated with elevated levels 

of potential contaminants,” said Elise Elliott, a fourth year graduate 

student who was the study’s lead author. 

Although preliminary water and environmental contamination 

studies are already in progress, crucial health-related information 

about a majority of the chemicals found in fracking fluids 

and wastewater is missing. “This reflects a broader issue in environmental 

health where we have a very poor understanding of 

the toxicity of many consumer products that we use,” Deziel said. 


March 2016 


9

NEWS 

neurobiology 

ALZHEIMER’S: AGE IS BUT A NUMBER 

New study links ageist attitudes to negative health outcomes 

►BY ARCHETA RAJAGOPALAN 

A recent study conducted by professor Becca Levy’s lab 

found a link between negative views on aging and the 

progression of Alzheimer’s disease. This research has the 

potential to improve current knowledge of the disease by 

shedding light on new targets for prevention. 

The cause of Alzheimer’s disease remains an active area of 

research. Some evidence indicates that Alzheimer’s traces 

back to a genetic mutation causing damage and death of 

neurons. Often, Alzheimer’s patients develop amyloid 

plaques, which are groupings of protein fragments that 

interfere with communication between cells. Disease 

sufferers may also have twisted fibers inside their brain 

cells, limiting the nutrition that reaches their neurons. 

While the biological basis, or biomarkers, for the disease 

is still being studied extensively, potential environmental 

causes are often overlooked. 

Levy’s research examined the relationship between a 

person’s perception of aging and the presence of Alzheimer’s 

biomarkers. To do so, participants in the Baltimore 

Longitudinal Study of Aging were monitored over many 

years for their views on aging and their brain development. 

The participants in the study took a survey gauging 

their beliefs on aging and subsequently underwent MRI 

scans looking for changes in hippocampal volume. The 

hippocampus is an area of the brain involved in the 

storage and processing of memories. This makes decreased 

hippocampal volume a good indicator of the onset of 

Alzheimer’s disease. Additionally, many volunteers who 

participated in the study posthumously gave their brains to 

science, allowing researchers to conduct brain dissections 

and look for the two primary Alzheimer’s biomarkers, 

plaques and twisted fibers. Researchers found a correlation 

between negative age stereotypes expressed on the survey 

and the progression of Alzheimer’s as judged by the 

presence of these biomarkers. 

Levy commented that studies in animals revealed similar 

results to those found in humans. “Studies that have placed 

animals in stressed environments have seen an increased 

incidence of plaques and tangles. We were anticipating 

this relationship between stressors—in particular, stress 

that might be caused by the negative age stereotypes that 

individuals take in from their culture and these Alzheimer’s 

biomarkers in humans,” Levy said. 

Another researcher involved in the study, biostatistician 

Martin Slade, supported this notion. “Your views of life 

affect how you take things in and how your body reacts. 

The more stress you put yourself under, the more your body 

will respond to it in a negative way,” Slade said. 

In contrast to current Alzheimer’s treatments, which 

focus on molecular approaches to treating the disease, this 

study highlights a new potential target. Slade explained that 

the applications of the research to the real world are easy to 

implement. “On a daily basis, people are bombarded with 

negative age stereotypes in advertising and on television. 

By reducing these age stereotypes that are presented to the 

general public, we can potentially reduce the frequency and 

severity of stress-related disorders like Alzheimer’s,” Slade 

said. 

Concurrently, Levy explained that people often form 

stereotypes early in life and maintain them as they 

grow older. She suggested that reinforcing positive age 

stereotypes in children as young as three or four years 

old could have a profound impact on their development 

and health. In fact, Levy and her team conducted another 

study in which they subliminally provided positive notions 

about aging via a computer program. They discovered 

that reinforcing positive age stereotypes that were already 

present had a beneficial effect on cognitive function. In this 

way, bolstering previously-formed positive age stereotypes 

may also help combat stress-related disorders. 

When asked about their next steps, Levy and Slade both 

cited the importance of finding a biological link between 

negative age stereotypes and Alzheimer’s disease in order 

to find a molecular target for Alzheimer’s prevention. They 

speculate that biological stressors may play a role in linking 

negative age stereotypes and disease onset. 

“While we were expecting these results, it’s still surprising 

when you have a theory and it turns out to be true— 

especially research which has such significant implications,” 

Slade said. 

IMAGE COURTESY OF BALTIMORE LONGITUDINAL STUDY 

►In the study conducted by Levy’s team, brain volume and 

hippocampus size were monitored using MRIs. 


physics 

NEWS 

THE MISSING LINK IN PARTICLE PHYSICS 

Neutrinos and the search for a new form of matter 

►BY MARY CHUKWU 

IMAGE COURTESY OF KARSTEN HEEGER 

►Yale postdoctoral researchers Thomas Langford and Nathaniel 

Bowden from Livermore National Laboratory with the PROS- 

PECT test detector performing test measurements at the High 

Flux Isotope Reactor. 


Dark matter? Particle accelerators? Higgs boson? Particle 

physics has left the public fascinated, and perhaps puzzled, by 

its potential implications. Current work on an obscure particle 

called the neutrino may leave even physicists grasping for answers. 

Researchers at the Yale Wright Laboratory led by professor 

Karsten Heeger currently design and implement experiments 

to investigate if neutrinos are a new form of matter. Such a discovery 

would require a major revision of the Standard Model of 

Particle Physics. 

According to the Standard Model of Particle Physics, neutrinos 

are neutral, massless elementary particles—matter that cannot 

be further subdivided. The neutrino can take three forms, 

the electron, tau, or muon neutrinos, and can only be acted upon 

by the universal weak force. The Standard Model attempts to explain 

the interactions in the subatomic world but cannot account 

for phenomena such as dark matter and dark energy. 

The Wright Lab’s research on neutrinos is groundbreaking 

because it shows that the assumptions of the Standard Model 

are even more flawed than previously thought. In 2016, Heeger 

shared the Breakthrough Prize in Fundamental Physics for three 

experiments showing that neutrinos can change their “flavor” as 

they travel through space. These changes in flavor—from electron 

to muon neutrinos, for example—are called neutrino oscillations 

and show that neutrinos have mass. 

“If you weighed all neutrinos in the universe, their combined 

mass would equal that of the mass of all the visible stars in the 

sky,” Heeger explained. 

Heeger’s group is involved in several neutrino experiments to 

determine the nature and mass of the neutrino and to search for 

the existence of a possible fourth form of neutrino—the sterile 

neutrino. One of these, Project 8, makes inferences about neutrinos 

based on electrons emitted from radioactive beta decay. 

Another project called the Cryogenic Underground Observatory 

for Rare Events (CUORE) studies a special form of nuclear 

decay called neutrino-less double beta decay and tests if 

neutrinos are their own antiparticles. Every particle has a counterpart 

antiparticle with the same mass but opposite charge; in 

the chargeless neutrino’s case, a quantum mechanical property 

called handedness varies instead. Antineutrinos are directly detected 

from nuclear reactors and indicate the presence of neutrinos. 

In ordinary double beta decay, two neutrons within a nucleus 

change into two protons and emit two electrons and two 

antineutrinos. However, in neutrino-less double beta decay, two 

neutrons are converted into two protons and two electrons are 

emitted—no antineutrinos. This is possible only if neutrinos are 

their own antiparticle. 

The Precision Oscillation and Spectrum Experiment (PROS- 

PECT) investigates neutrinos taken from an active nuclear reactor. 

What distinguishes this project is its short baseline, or 

distance between the neutrino source and detector—10 meters 

rather than the usual hundreds. The experiment measures the 

variation in neutrino flavor—the neutrino oscillation—over 

short distances. Results could provide evidence for the sterile 

neutrino, which is unaffected by the weak force and thus an entirely 

new form of matter. 

The discovery of the sterile neutrino would be no less than a 

“paradigm-shift for the whole [scientific] community,” said Danielle 

Norcini, a graduate student working on PROSPECT. 

Findings about whether neutrinos are their own antiparticles 

and whether sterile neutrinos exist could require a revision of the 

long-standing Standard Model of Particle Physics. 

“If neutrinos are their own antiparticles, then there has to be a 

new term in the [Standard Model] that describes how particles 

get their mass…there has to be more than just the Higgs boson. 

If we discover sterile neutrinos, then there would have to be a 

whole new class of matter [added to the theory],” Heeger said. 

Aside from its implications in theoretical physics, neutrino research 

has tangible applications. Beyond the laboratories of experimental 

physics, advanced forms of neutrino detection would 

prove valuable to nuclear reactor monitoring. Neutrinos from a 

reactor core can describe the contents of the reactor, including 

the type of radioactive fuel used and the type of radioactive decay 

occurring. Some of the unique advantages of neutrino detection 

include its harmlessness, as neutrinos do not affect humans 

physically, as well as the neutrinos’ ability to pass through 

any barrier unimpeded—no man-made method can hide their 

presence. 

In addition, neutrinos are integral to the grand scheme of the 

universe as we know it. 

“Without neutrinos, supernovae wouldn’t happen. Supernovae 

are important for producing the elements that we are made of,” 

Heeger said. 

Future Wright Lab research will further the scientific understanding 

of neutrinos and particle physics with applications that 

extend into cosmology and astrophysics. 

March 2016 


11

the 

FLOW 

of 

FLAVOR 

by Diane Rafizadeh | art by Christina Zhang 

Put a jellybean in your mouth and pinch your nose. 

What do you taste? Only sweetness—nothing else. But 

let go of your nose, and suddenly you taste the real 

flavor: cherry, maybe, or lemon. Until now, it was not 

entirely clear why this was so. 

In a recent paper published in the Proceedings 

of the National Academy of Sciences, a 

team of researchers headed by Yale University 

Professor of Neuroscience Gordon Shepherd 

has come up with a potential explanation. 

Through collaboration with engineers at Yale’s 

Department of Engineering and Center for 

Engineering Innovation and Design (CEID), 

Shepherd and his colleagues have uncovered 

a physiological explanation for this enhancement 

of smell and taste when exhaling as compared 

to inhaling. As it turns out, the shape of 

the airway causes the airflow during exhalation 

to actively transport food odors to olfactory 

neurons. This discovery could have implications 

ranging from why food is less appetizing 

when we are sick to why we crave the food we 

do. 

The special case of smelling while exhaling 

Retronasal olfaction occurs during exhalation, 

when one smells “volatiles,” or odorant 

molecules, that originate from the mouth. Orthonasal 

olfaction works similarly, just that it 

occurs as one breathes in and smells volatiles 

from the outside environment. Both processes 

involve the oropharynx, which is the middle 

part of the throat around the back of the tongue, 

as well as the nasopharynx, the upper part of 

the throat above the nose. The actual sensation 

of smelling the food that we eat occurs when 

volatiles from food are released into the back 

of the mouth, then transported by exhaled air 

from the oropharynx to the nasopharynx. The 

ordorants then interact with olfactory receptor 

cells in the nasal cavity, sending a neural signal 

to the brain that we perceive as smell. Shepherd’s 

goal was to find an explanation for the 

dynamics of retronasal airflow by examining 

the shape of the throat and head. 

Prior to Shepherd’s study, it was not clear 

how the transport of food volatiles from the 

mouth and through the airway occurred. But 

when they looked at how air flowed through 

different parts of the airway, Shepherd and his 

team discovered the importance of an area that 

connects the mouth to the oropharynx and 

that they labeled the ‘virtual cavity.’ During 

inhalation, the speed of airflow is large in the 

oropharynx but close to zero in the virtual cavity, 

meaning that food volatiles remain in the 

mouth and do not enter the airway. In contrast, 

during exhalation, the speed of airflow is much 

greater in the virtual cavity; its shape is such 

that the food volatiles are transported from the 

mouth into the main airflow, which then carries 

these odorants upwards to the nasal cavity 

where they are detected by olfactory neurons. 

The result, from analysis of retronasal olfaction, 

is that our sensations of smelling the food 

in our mouths are strongest when exhaling be- 

www.yalescientific.org

physiology 

FOCUS 

cause that is the only time during the breathing 

cycle in which food volatiles are actively 

transported to olfactory neurons. At the same 

time, when we inhale, the shape of the airway 

minimizes transport of food volatiles toward 

the lungs. 

An interdisciplinary undertaking 

The method by which Shepherd and his 

team studied the shape of the airway and the 

speeds of airflow in different parts of it highlights 

the many advantages of interdisciplinary 

research. 

First, Shepherd’s team—located in the neuroscience 

department—obtained a 3D image 

of one human airway from collaborating 

physicians at the medical school. The CT scan 

was originally taken for a different study. Shepherd’s 

team then took this data to Yale’s CEID, 

where engineers aided in creating a three-dimensional 

model of the airway. With the help 

of collaborator Joseph Zinter, assistant director 

of the CEID, the team used a 3D printer to 

build a model that functions just like the human 

airway. They added pumps to each end 

to simulate the passage of air from one part to 

another. 

Nicholas Ouellette, then an associate professor 

of mechanical engineering and materials 

science at Yale, and first author Rui Ni, a postdoc 

at Yale at the time of the work, brought new 

meaning to the model; the researchers were experts 

in fluid mechanics, the branch of physics 

and engineering that studies how the laws of 

forces and motion apply to fluids. To best track 

movement of fluid, they pumped water rather 

than air through the model airway. By seeding 

the water with fluorescent particles, they then 

tracked the movement of these particles with 

LED light and determined which parts of the 

airway had the strongest and weakest airflows 

by comparing the velocities of the particles. 

An adaptive advantage 

This study provides major evidence for a 

two-system model for breathing; orthonasal 

smell is for breathing in and allows us to catch 

whiffs of odorants in the air, while retronasal 

smell is for breathing out, which aids us 

in smelling the food and drink we consume. 

Shepherd believes that this separation between 

PHOTO BY DIANE RAFIZADEH 

►In professor Gordon Shepherd’s book, Neurogastronomy, 

he describes how we perceive 

flavor, as well as how it affects our lives and 

society. 

the two systems is an adaptive advantage. Retronasal 

smell involves an adaptation of the airway 

that enhances transport of food volatiles 

to the nose, allowing us to “sample” the food in 

our mouths before we swallow it so that we can 

choose not to continue eating anything unpleasant. 

At the same time, the pathway minimizes 

transport of food volatiles to the lungs, 

preventing anything potentially harmful from 

entering the lungs. 

Shepherd acknowledged that the fascinating 

findings of the study were limited by how the 

model airway was constructed based on just 

one test subject. Still, the researchers believe 

that the function of retronasal smell is universal, 

and they are looking to conduct similar 

studies in people of different ages, races, and 

genders. 

“Retronasal smell may help explain why 

children eat what they do and often crave 

things that may not be good for them,” Shepherd 

said. He also speculates that retronasal 

airflow might help explain why it’s difficult to 

taste food while having a cold. More broadly, 

retronasal smell might be affected by different 

pathologies in the back of the mouth, such as 

sore throat or a stroke that leaves someone 

without the full ability to breathe in and out or 

swallow. 

“It’s still true that most interest in smell is in 

perfumes and the like, which we sense when 

breathing in,” Shepherd said. “One of the 

things I’m trying to do is to emphasize that 

retronasal smell is one of our most important 

senses. It’s not just for aesthetic things, but is at 

the very core of what makes us human, and we 

use it every day at every meal.” 

ABOUT THE AUTHOR 

DIANE RAFIZADEH 

DIANE RAFIZADEH is a freshman Chemistry major in Jonathan Edwards 

College. She is a Staff Writer for the Yale Scientific Magazine and is interested 

in research in medicinal chemistry. 

THE AUTHOR WOULD LIKE TO THANK Professor Shepherd for his time 

and for his enthusiasm in sharing his research on retronasal olfaction. 

FURTHER READING 

Rowe TB, Shepherd GM. February 15, 2016. Role of ortho-retronasal 

olfaction in mammalian cortical evolution. Journal of comparative neurology 

(1911) 524, no. 3, (accessed February 11, 2016). 


March 2016 


13

FOCUS 

neuroscience 

When you grow up with three siblings, 

you quickly learn to treat groceries 

like a scarce resource. My sisters and 

I were particularly fond of Tropicana orange 

juice, no pulp. A carton never lasted long. I 

poured more for me, less for the others—that 

way, there would be more juice left for me to 

drink tomorrow. But if the carton was about to 

expire, if our mom threatened to throw it out, 

of course I would rather have my sister drink 

the juice than let it go to waste. 

As it turns out, my sisters and I had a lot in 

common with monkeys. 

Steve Chang, a professor of psychology and 

neurobiology at Yale, had rhesus macaques play 

a dictator game: One monkey could decide how 

to allocate juice between himself and another 

monkey. Almost always, a monkey chooses to 

reward only himself rather than both him and 

his peer, even if he receives the same quantity of 

juice regardless. But if the choice is between his 

peer getting the juice and no one receiving it, he 

opts to reward the other monkey. 

Rhesus macaques are inherently social. The 

cap on their generosity could be the need to 

compete for fluids in a natural habitat, which 

leads them to reward only themselves instead of 

self and other (and which caused some selfish 

juice hoarding in my childhood home). Chang 

and his team wanted to look deeper into these 

social decisions. They zoomed in on the brain 

while a monkey played dictator, uncovering the 

crucial role of the amygdala, value-mirroring 

neurons, and the hormone oxytocin. 

Humans and primates are social creatures— 

we live in groups, form relationships, divide 

and distribute resources. For both of us, 

healthy cooperation is vital. Strong relationships 

and social status grant access to scarce 

resources. Some scientists have even suggested 

that empathy and generosity are the basis for 

advanced civilization. Understanding social decision-making 

is thus an important line of inquiry 

for researchers. Chang’s investigation of 

the brain structures that drive prosocial versus 

antisocial behavior could inform treatments 

for autism and other disorders linked to social 

deficits. More broadly, this research impacts all 

of us who inhabit a social world. 

Empathy, hardwired 

Early brain imaging studies found that the 

amygdala is active when someone experiences 

fear. For years thereafter, it was thought that 

the structure was only involved in aversion and 

negative reactions. In fact, the amygdala is a 

center for all sorts of emotions, and recent research 

has revealed its broader range of functions. 

“Our goal was to look at the amygdala 

and determine whether it’s involved in processing 

across self and other,” Chang said. 

In short, the answer was yes. Chang’s findings 

add to our understanding of the amygdala and 

all that it does, and they offer a key piece in the 

effort to map a social decision across the brain. 

The team took recordings from individual 

neurons in the basolateral amygdala, which is 

one unit of the whole structure. Chang outlined 

the possibilities: These neurons might 

only show a spike in activity when the monkey 

himself receives juice. In this case, the amygdala 

would be self-oriented, coding for personal 

rewards. Alternatively, the group might have 

identified some neurons that are active for personal 

rewards, and others that fire rapidly when 

someone else gets a reward. 

Chang confirmed a third potential outcome: 

“The basolateral amygdala has neurons that 

treat value for self and other in a categorically 

same manner,” he said. The same neuron that 

fires more rapidly when I receive juice is activated 

by someone else receiving juice. 

What the team found in the amygdala is a 

type of mirror neuron. But these nerve cells 

are not mirroring in the classical sense, when 

seeing someone scratch her head activates the 

same regions in my brain that would light up 

if I were to scratch my own head. Scientists are 

realizing that mirror neurons populate areas in 


neuroscience 

FOCUS 

the brain beyond motor cortex. Chang’s 

amygdala cells were mirroring value, 

and the suggestion is that these neurons 

might allow for emotional contagion, 

which occurs when someone else’s feelings 

affect your own. 

Value-mirroring neurons offer a neural 

framework for empathy and generosity—they 

could explain our ability to feel 

for another person and our inclination 

to give. In humans, fMRI has displayed 

that another brain area, the ventral striatum, 

lights up similarly when you buy 

an item for yourself and when you donate 

to charity. Value-mirroring neurons 

could be a cue to someone else’s 

emotions, leading us to empathize with 

a friend’s pain and to feel good about donating 

money to someone in need. 

“Our work squarely fits in with prior 

work identifying the amygdala in one’s 

own emotional experience,” said Michael 

Platt, a University of Pennsylvania 

professor and senior author on this 

paper. Amygdala neurons fired when a 

monkey received a reward, encoding a 

pleasant reaction. “It also supports the 

notion that your own emotional experience 

is the foundation by which you 

understand another’s experience,” Platt 

said. The same positive emotion-coding 

neurons were active when a monkey donated 

juice. 

We have reason to believe that the human 

amygdala functions similarly. In 

addition to the social behaviors we share 

with rhesus macaques, several studies 

show overlap in biology and brain circuitry, 

Platt said. 

According to John Pearson, a co-author 

on this paper and a professor in 

the Duke Institute for Brain Sciences, 

value-mirroring neurons are important 

because they provide some clarity as to 

how the brain operates in value formation. 

How we define value is complicated. 

“If we’re both getting bonuses at the 

end of the year, I could be happy about 

my reward, or I could look at the situation 

as me getting less money than you,” 


Pearson said. There are multiple ways to 

assign value, and in all likelihood, both 

processes are happening in the brain. 

But now we know that certain neurons 

in the amygdala match value for self and 

other. 

Neuroscientific studies, especially 

those with a brain imaging component, 

are vulnerable to the logical fallacy of 

reverse inference: When psychologists 

believed that the amygdala coded primarily 

for fear, noticing a spike in amygdala 

activity led to conclusions that the 

individual must be experiencing aversion. 

“What this paper adds to,” Pearson 

said, “is the diversity of processes we can 

associate with the amygdala. It’s much 

more than a fear center.” 

A prosocial pick-me-up 

IMAGE COURTESY OF STEVE CHANG 

►The rhesus macaque is a highly social creature. 

These monkeys live in groups, exhibit 

nurturing behavior, and use social status to 

procure scarce resources in the environment. 

Next, the researchers had monkeys 

play the dictator game after delivering 

oxytocin to the basolateral amygdala. 

The hormone increased prosocial behavior—monkeys 

were more likely to 

reward both self and other instead of 

taking juice only for themselves. 

Prior research has pointed to oxytocin 

as a method to increase generosity. 

When people are given a sum of money 

and are asked to donate a portion to 

another player, they donate more after 

a dose of oxytocin. But in humans, it 

is impossible to target any hormone to 

one specific cluster of neurons, so these 

studies cannot elucidate how oxytocin 

is prompting prosocial behavior. Using 

the rhesus macaque as a model, the team 

highlighted the amygdala as a mechanism 

by which the hormone may be affecting 

the brain. 

Chang’s findings are consistent with 

hypotheses at the forefront of the field, 

said Jennifer Bartz, a professor at Mc- 

Gill University who studies the nuanced 

effects of oxytocin on different populations 

and in different social situations. 

One prediction is that the hormone 

enhances our sensitivity to social cues. 

Indeed, Chang noted that dictator monkeys 

injected with oxytocin paid more 

attention to their counterpart. They 

spent longer looking at the other player. 

Perhaps in improving a monkey’s social 

gaze, oxytocin made the animal more 

generous. 

Another explanation, Bartz said, is 

that oxytocin increases sensitivity to social 

rewards. In this case, the hormone 

motivates us to affiliate, because a social 

connection will boost our positive feelings. 

Value-mirroring neurons support 

this hypothesis, and perhaps oxytocin 

in the amygdala sparked the dictator 

monkey’s greater desire to be prosocial 

towards his peer. 

Individuals with autism have trouble 

maintaining eye contact. They often 

struggle to intuit the mental states 

of other people, which is why empathy 

and generosity are challenging. Chang 

hopes that his findings are informative 

in helping people with social impairments, 

which includes autism, as well as 

conditions like schizophrenia and psychopathy. 

A few clinical trials in their 

early stages are testing oxytocin drugs 

March 2016 


15

FOCUS 

neuroscience 

►LEFT: Mirror neurons lead to 

mimicking behavior in rhesus 

macaques, a primate species 

that is similar to humans in 

many ways. Another type of mirror 

neuron exists in a monkey’s 

amygdala, perhaps allowing him 

to experience another’s emotions 

as if they were his own. 

IMAGE COURTESY OF STEVE CHANG 

IMAGE COURTESY OF YALE UNIVERSITY 

►RIGHT: Steve Chang is an assistant 

professor of psychology 

and neurobiology at Yale. He is 

interested in the neuroscience 

of a social decision, and he has 

analyzed many areas of social 

processing in the brain. 

on children and adults with autism spectrum 

disorder. 

Although patients are excited about 

this, Bartz said we are still a long ways 

away from developing an effective oxytocin 

treatment. First, scientists must 

clarify the hormone’s mechanism of action, 

and they should explore how it influences 

prosocial behavior in different 

situations and for various patient groups. 

Bartz and her colleagues have found that 

oxytocin can exacerbate distrust in people 

with trust-related insecurities, which 

causes antisocial behavior. 

Despite unanswered questions and 

technological limitations, the knowledge 

of oxytocin and the amygdala that 

has emerged from this research could 

eventually prove useful in treating individuals 

with social deficits. The causes 

of autism, schizophrenia, and psychopathy 

remain elusive. Pearson said this 

research elucidates the brain systems 

underlying a social decision, and understanding 

these systems is the first step to 

unveiling why and how they go awry. 

Mapping a social decision 

While the neural underpinnings of social 

impairments are still hidden, there 

are also many unknowns regarding the 

neuroscience of prosocial behavior. 

What does a social decision look like 

across the brain? 

Chang’s prior work has zoomed in 

on other brain regions while monkeys 

play the dictator game. Neurons in the 

orbitofrontal cortex tend to fire in response 

to one’s own reward. “This area 

doesn’t seem to care much about what 

the other monkey gets,” Chang said. 

“So these neurons are selfish, in a way, 

or self-referenced.” In the anterior cingulate 

sulcus, neurons are most active 

when the dictator does not receive the 

juice, meaning these cells encode for a 

“foregone reward,” he said. 

In the anterior cingulate gyrus, Chang 

has found a mix of cells. Many neurons 

in this area are other-referenced: they 

show the greatest activity in response 

to another individual’s reward outcome. 

But the anterior cingulate gyrus also 

contains self-referenced neurons that 

match the cells in the orbitofrontal cortex, 

as well as value-mirroring neurons 

that resemble cells in the amygdala. 

Each of these four areas uses a different 

approach to calculate reward value 

between self and other. 

“Then, they all come together magically 

to generate prosocial or antisocial 

behavior,” Chang said. “Evidence points 

to specialization in each of these regions, 

and now we need more insight into how 

these areas are talking to each other.” 

The psychologists are also curious 

about the familiarity factor. How do 

value-mirroring neurons respond differently 

to close friends compared to 

strangers? If my sisters and I were reluctant 

to pour orange juice for each other, 

we definitely disliked sharing when people 

came over. The juice stayed within 

the family. 

Some of Chang’s future projects will 

explore these areas as his team continues 

to sketch social decisions in the brain. 

There is still vast potential to accumulate 

new knowledge on the neuroscience 

of empathy, generosity, and prosocial 

behavior. Because how to share juice is 

just one of life’s many social decisions. 


PAYAL MARATHE 

PAYAL MARATHE is a senior studying psychology and neuroscience. In past 

years, she has served as features editor and editor-in-chief of this magazine. 

THE AUTHOR WOULD LIKE TO THANK Steve Chang, John Pearson, 

Michael Platt, and Jennifer Bartz for being so generous with their time in 

discussing these topics. 


Chang, Steve WC, et al. “Neural mechanisms of social decision-making in the 

primate amygdala.” Proceedings of the National Academy of Sciences112.52 

(2015): 16012-16017. 


ecology 

FOCUS 

IS TIME 

RUNNING 

OUT? 

Scientists 

by Amanda Mei | art by Ashlyn Oakes 

rethink 

the idea of mass 

extinction 

From the asteroid strike that ended the reign of dinosaurs 

to the question of whether we are living through a sixth 

mass extinction today, mass extinctions have captured 

the public imagination. Now, a group of scientists is 

challenging how mass extinctions are interpreted, 

and they argue for species rarity as a more useful and 

accurate way to measure ecosystem collapse. 


March 2016 


17

FOCUS 

ecology 

Comparing the events of today to distant 

events in evolutionary time is 

difficult. Scientists today can only attempt 

to piece together the story of how species 

and their environments changed over 

time using the fossil record. These records 

form over hundreds of thousands of years 

as marine organisms die, fall to the ocean 

floor, and accumulate in layer upon layer of 

rock. They see some layers with many species 

and others with very few, and they infer 

that the layers where many species are suddenly 

lost from the rock record bespeak of 

times of rapid and rampant ecosystem collapse 

called mass extinctions. 

But since human history is only a split 

second in fossilized time, the high extinction 

rates of today may not necessarily correspond 

to species loss on the scale of past 

mass extinctions. The notion of mass extinctions, 

seared into the public consciousness 

by paleontologists Jack Sepkoski and 

David Raup in their 1982 landmark paper, 

does not capture nuances of biodiversity crises 

past or present. 

Species become rare before they go extinct. 

We see species becoming rare today. 

The researchers, including lead author and 

Yale assistant professor of geology Pincelli 

Hull and Smithsonian Institution curator 

Douglas Erwin, now propose species rarity 

as a reliable way to measure the extent of 

modern ecological crises. 

But the researchers question whether 

present biodiversity changes necessarily 

constitute a sixth mass extinction. We 

need to change how we compare ecological 

changes today to the five past mass extinctions 

to address the question. 

Even so, Simon Darroch, assistant professor 

at Vanderbilt University, and another author 

of the paper, said we should be worried 

about the rapid decline of marine species 

such as clams and corals. The Elkhorn coral, 

for instance, used to be the most abundant 

species in the Caribbean 3,000 years 

ago. Now, although not extinct, the species 

is rare. 

Comparing then and now 

Hull had been frustrated for years by the 

idea of the “sixth mass extinction.” After 

researching the catastrophic K-T mass extinction 

that wiped out most dinosaurs 65 

million years ago, Hull deeply questioned 

whether scientists could compare present 

ecological changes to past mass extinctions 

using information preserved in fossils. She 

was skeptical of comparing information 

across vastly different time scales. “The way 

extinction is preserved in the fossil record is 

so different than the way that we see it today,” 

Hull said. 

Extinction rates can appear to be low 

in the fossil record due to its preservation 

of long time intervals, according to Hull. 

Whereas scientists use fossil records— 

which represent tens or hundreds of thousands 

of years in a couple of centimeters— 

to estimate extinction rates during past mass 

extinctions, scientists measure current rates 

on much shorter time intervals. 

Hull explained the fallacy using an analogy. 

Imagine we have a man crossing the 

street in a minute. A clock that measures 

time in seconds would indeed show the man 

crossing the street in a minute, but another 

clock that measures time in years would 

tell us that the same man crossed over the 

span of a year. No wonder scientists using 

fossil records come up with past extinction 

rates 10 times lower than present measurements—and 

smear out sudden, dramatic 

extinction events. 

Darroch likewise said the fossil record 

was an amazing research tool, but it averaged 

processes over long intervals without 

really capturing ecosystem collapse. According 

to Erwin, the fossil record was not 

good enough to resolve events other than 

which species were absent or present during 

past mass extinctions, and he said scientists 

had not paid enough attention to other ecological 

factors. 

In a workshop on extinction at Arizona 

State University’s Institute of Human Origins, 

Hull, Darroch, and Erwin asked how 

scientists could better compare present ecological 

processes with past mass extinctions 

using the fossil record. They discussed the 

issue over lunch. By that evening, the team 

had drafted the paper that was not exactly 

a study or review, but an idea—about how 

scientists can compare past mass extinctions 

and present ecological changes using species 

rarity instead of extinction rates. “By measuring 

rarity, we actually do get rid of that 

problem of smearing things out,” Hull said. 

Changing scenarios 

The researchers outlined three scenarios 

for how ecosystems may change 


ecology 

FOCUS 

during mass extinctions, in order to recapture 

some of the nuances lost in the fossil 

record. 

In the first scenario, ecosystems collapse 

instantaneously. A trigger, such as the asteroid 

impact that hit Earth during the K-T 

extinction, causes most species to become 

extinct within a few hundred years. Scientists 

often assume this first scenario to be 

the case when they see sudden disappearances 

of species from the fossil record. 

In the second scenario, mass extinction is 

delayed. After a trigger causes some species 

to become extinct, the ecosystem changes 

in such a way that it cannot sustain itself. 

The initial extinctions lead to more extinctions, 

which lead to even more extinctions, 

and the vicious cycle eventually leads to 

mass extinction. 

But the researchers were more interested 

in the third scenario, which does not assume 

species go extinct when they disappear 

from the fossil record. The trigger in 

this scenario does not lead to any extinctions; 

rather, it leads to some species becoming 

rare. If those species had once been 

common and important in the ecosystem, 

their rarity increases the risk of total ecosystem 

collapse. This scenario is called “elevated 

extinction risk.” 

So far, scientists cannot distinguish between 

the scenarios in the marine fossil record. 

Hull and her team came up with these 

hypotheses about how ecosystems change 

in mass extinctions, but others must test 

them. Darroch has taken up some of the 

challenges by designing a model to test how 

changes in the ecosystem affect fossils. By 

distributing species across a map and asking 

what happens when common species 

become rare and when rare species become 

extinct, he can see how much fossils 

preserve. The tests have gone on for about 

four months, and Darroch anticipates four 

more—not to mention the years of further 

work he and other scientists must do to 

answer questions about the ways in which 

mass extinction scenarios are playing out in 

the world today. 

Drawing the line 

The Elkhorn coral—once common, now 

rare—provides one clue that ecosystems 

face a greater risk of mass extinction in the 

present day. 

Hull and other researchers may object to 

IMAGE COURTESY OF PINCELLI HULL 

► A team led by Yale assistant professor of 

Geology and Geophysics Pincelli Hull has a 

new idea for comparing current ecological 

crises to past mass extinctions—using species 

rarity instead of extinction rate. 

the term “sixth mass extinction” because it 

implies that scientists have made a reliable 

comparison between past mass extinctions 

and present ecosystem conditions using 

fossil records. But the researchers do not 

deny that we are living through a time of 

massive ecological change—caused mainly 

by us. 

In their paper published in Nature in 

December 2015, the team members describe 

how marine species like clams and 

coral have declined in absolute numbers 

and geographic area due to human activities 

such as overfishing and pollution. The 

species have become what researchers call 

“ecological ghosts,” no longer performing 

their function in the ecosystem. Elkhorn 

corals, for example, no longer provide a 

home for fishes. 

Based on these observations, extinction 

on a greater scale suddenly seems more 

likely. Hull sees the intensive, destructive 

activity of human beings as a thin line in 

the fossil record—similar to the dark brown 

line between the Cretaceous and Paleocene 

periods caused by the K-T extinction. But 

she objects to another idea regarding how 

humans are impacting the planet. “I don’t 

think we’re entering the Anthropocene,” 

Hull said, referring to the idea that human 

activity is forcing the planet into a new geologic 

period. “I think that what we’re doing 

will end up looking like the boundary between 

two different layers.” 

Interpreted in one way, Hull predicts an 

apocalyptic future. She claims that human 

beings cannot last another geologic period, 

tens of thousands of years, if they keep up 

their destructive activities. But under a different 

light, Hull is optimistic. She said that 

on “good days,” usually when she is at Yale, 

she believes humans can make it across the 

line, head off mass extinction, and enter a 

period quite unlike the Anthropocene. 

Erwin agrees with Hull that defining 

a new geologic era centered on humans 

would not save any species from becoming 

rare or extinct. But Darroch said the concept 

was a good public relations tool. He 

urged us to view modern ecological changes 

from a new perspective. “If you were an 

alien investigating a hundred years from 

now, and you were to look at the rock record, 

all the stuff that we’re doing will be 

preserved in a thin smear,” Darroch said. 

A thin smear, representing a few hundred 

years of human activity and massive ecological 

change, may be either a starting line 

or a finishing line—depending on our perspective 

on ecological crises. 


AMANDA MEI 

AMANDA MEI is a sophomore Environmental Studies major in Berkeley 

College. She is a former Layout Editor of the Yale Scientific Magazine interested 

in the relationships between human beings, wildlife, and the environment. 

THE AUTHOR WOULD LIKE TO THANK Pincelli Hull, Simon Darroch, and 

Douglas Erwin for their thoughtful interviews, as well as their dedication to 

understanding ecosystem dynamics in present and past ecological crises. 


Crutzen, P. J. & E. F. Stoermer (2000). “The ‘Anthropocene’”. Global Change 

Newsletter 41: 17–18. 


March 2016 


19

As we grow older, our immune systems begin to falter. 

Colds hit harder. Responses to vaccines turn weaker. One of the primary culprits in the deterioration of immunity 

with age is the failure of the thymus, a tiny organ tucked between the heart and the breastbone that is 

vital in the production of disease-fighting T cells. With age, this organ becomes gorged with fat, compromising 

our ability to make new T cells. So when we are old and the winter sniffles hit, they hit hard. 

Now, a study led by Vishwa Deep 

Dixit, professor of Immunobiology 

and Comparative Medicine at the 

Yale School of Medicine, has uncovered a 

hormone that may help curb thymic breakdown. 

Known as Fibroblast Growth Factor 

21 (FGF21), this hormone may stimulate the 

thymus and prevent our immune systems 

from going downhill as we age. This finding 

provides new biological insight into the 

factors involved in thymic aging. It may also 

offer a promising treatment to boost immunity 

in the elderly and in cancer patients after 

bone marrow transplants. 

A first clue 

Most organs deteriorate with age, but the 

thymus is notable for being one of the first to 

go. The early collapse of the thymus is problematic 

because this small organ has an important 

function. The thymus nurses young 

T cells as they mature, providing them with 

a rich environment of signals to guide their 

development. The mature T cells then leave 

the thymus and go on to establish a vast population 

of powerful, highly specific immune 

warriors that are critical in protecting our 

bodies against infection. 

However, this healthy T cell nursery does 

not stick around for long. Instead, as we 

grow older, the thymus becomes packed 

with fat cells. By the age of 45, long before 

most other organs have shown any signs 

of aging, the thymus is over 70 percent 

fat, Dixit said. While it is not clear where 

these fat cells come from or why they are 

there to begin with, the damage they do 

is devastating. By the time we reach our 

mid-forties, when our T cells journey from 

the bone marrow where they are formed to 

their thymic nursery, they arrive to find it 

in shambles—jam-packed with fat cells, its 

architecture collapsed. Any hope of T cell 

maturation in this environment is practically 

nonexistent, and the release of new, 

mature T cells from the thymus grinds to 

a halt. This explains why older people have 

weaker immune systems. Yet why and how 

the thymus falls into disarray is still not 

fully understood. 

A clue to the dynamics of thymic fatty 

deterioration came almost seven years 

ago, when Dixit and his colleagues were 


medicine 

FOCUS 

To Immunity and Beyond 

recruiting the heroic hormone that rescues aging immune systems 

By Malini Gandhi 

Art By Ashlyn Oakes 

analyzing mice raised on a low-calorie 

diet. Calorie restriction promotes fatty 

acid breakdown to continue to fuel 

the body, which has long been linked 

to increased lifespan. When researchers 

looked at the thymi of these calorie-restricted 

mice, they noticed something 

surprising—the thymi were remarkably 

healthy. Unlike the thymi of mice 

fed on normal diets, the thymi of these 

mice had intact structures and were relatively 

free of fat. Curious, Dixit and his 

colleagues analyzed what proteins were 

being expressed at elevated levels in the 

thymi of calorie-restricted mice. The 

hormone FGF21 was one of them. 

At the time, FGF21 was known 

primarily as a hormone secreted by the 

liver that promotes fatty acid degradation 

during times of energy deficit; it was also 

known to extend lifespan. Dixit wondered 

if this hormone could help mediate the 

beneficial effects of calorie restriction 

on thymic aging by promoting the 

breakdown of fatty acids, thus preventing 

the thymus from becoming crammed with 

fat and slowing the organ’s deterioration. 

“Our thinking was that if we could 

elevate FGF21 within the thymic microenvironment, 

it would prevent lipids 

from accumulating in the thymus and 

help maintain thymic architecture,” Dixit 

said. “We would essentially be mimicking 

calorie restriction.” 

Good as new 

Armed with this promising initial finding, 

Dixit and his colleagues first set out 

to determine where, when, and how much 

FGF21 is expressed in the thymus. Intriguingly, 

it turns out that the expression of 

this hormone in the thymus steadily drops 

with age. It also turned out that just 1% of 

cells in the thymus—a population of cells 

called thymic epithelial cells (TECs)—are 

responsible for both producing and responding 

to this hormone. The thymus is 

mainly populated by immune cells, but it 

is the TECs that are key players in guiding 

the development of T cells. “The fact 

that FGF21 was coming from and acting 

on such an important cell type for thymic 

function suggests that this molecule must 

be really important in the thymic environment,” 

Dixit said. 

The researchers took the logical next 

step. They decided to investigate what 

would happen if they ramped up expression 

of FGF21. They aged mice that were 

genetically modified to express high levels 

of this hormone and then took a look at 

their thymi. What they found was exciting: 

the thymi of elderly mice that were 

engineered to overexpress the hormone 

looked very similar to those from the calorie-restricted 

mice. Compared with mice 

with normal levels of the hormone, these 

mice had fewer fat cells, more T cells and 

certain TECs, and more intact thymic architecture. 

“The thymus of a one-year-old 

mouse that overexpressed FGF21 looked 

like the thymus of a four-month old mouse 

with normal FGF21,” Dixit said. 

In the mice with more FGF21, a healthier 

thymus meant a more robust immune 

system. The researchers found that the 

mice with more of the hormone were 

producing more new T cells. By slowing 

the deterioration of the thymus, FGF21 

protected the mice from immune system 

collapse that comes with age. On the flip 

side, the researchers found that in mice 

in which the FGF21 gene was knocked 


March 2016 


21

FOCUS 

medicine 

‘ 

What 

metabolic 

scientists have long considered to be solely a 

hormone actually has another crucial function. 

out, thymic degradation was accelerated, 

and the number of new T cells produced 

was limited. Without this hormone, the 

thymus collapses too soon. 

An unknown mechanism 

While the power of FGF21 in preventing 

thymic degradation is clear, its exact 

mechanism is still unknown. One 

potential explanation, which is in line 

with its previously established metabolic 

functions, is that this hormone promotes 

breakdown of fatty acids in the thymus. 

“This could prevent the thymic stroma 

from becoming infiltrated with lipids and 

help maintain the microenvironment so 

that the thymus can continue making T 

cells,” Dixit said. While this explanation 

seems plausible, it has not yet been 

demonstrated. 

Dixit thinks FGF21’s role in promoting 

fat breakdown might not be the whole 

story. His suspicion stems from the 

surprising fact that this signal is produced 

in the thymus at full blast in the young, 

even though there is very little fat in the 

thymus at this point in time. This suggests 

that the hormone might have another 

function in addition to fat clearance that 

acts early on. Dixit speculates that FGF21 

may have an additional role in triggering 

signaling pathways in TECs associated 

with cell division, thus allowing these 

crucial epithelial cells to proliferate and 

maintain themselves. If this proves true, 

it would mean that what scientists have 

long considered to be solely a metabolic 

hormone actually has another crucial 

function. Evolutionarily, this possibility 

raises interesting questions about which 

came first, FGF21’s function in metabolism 

or in cell growth. 

With these issues still up in the air, 

Dixit said the next step is to investigate 

the hormone’s molecular mechanism. His 

group is currently working on dampening 

or elevating FGF21 levels in just the thymi 

of mice to eliminate its potential effects on 

other parts of the body, and then homing 

in on exactly how this hormone regulates 

thymic epithelial cells. 

Therapeutic promise 

Though its mechanism is still being 

clarified, the ability of FGF21 to slow 

thymic deterioration is clear, and could be 

harnessed therapeutically. Drugs that raise 

its levels could be used to improve thymic 

function and enhance T cell production in 

the elderly, offering hope that immunity 

can be boosted in older individuals. 

Additionally, this hormone holds 

promise in treating cancer patients who 

have undergone bone marrow transplants. 

Prior to bone marrow transplants, a 

patient’s old, damaged set of blood 

and immune cells is wiped out with 

chemotherapy. Then, their unhealthy bone 

marrow is replaced with fresh, healthy 

bone marrow, which is used to repopulate 

their blood and immune cells. But if the 

patient is over the age of 45, the new T 

cells generated from the transplanted 

bone marrow will arrive at the thymus for 

maturation only to find it old and packed 

with fat, meaning that the patient is unable 

to produce any new, mature T cells. 

Since their original T cells would have 

been wiped out by chemotherapy, the 

Art By Aydin Aykol 

patients are left without any T cells, 

rendering them extremely susceptible 

to infection. To make matters worse, the 

few original, unhealthy T cells that were 

somehow able to survive chemotherapy 

can take hold and start proliferating in 

the patient’s body. According to Dixit, this 

nightmare situation could be remedied 

by treatment with FGF21—by rescuing 

thymic function, this hormone could 

allow these patients to start replenishing 

their T cell populations. 

Yet more research is needed before this 

hormone can be administered as a drug to 

improve thymic function. Moving beyond 

experiments conducted using mice 

genetically engineered to overexpress the 

hormone, Dixit’s lab is now attempting 

to deliver the hormone in the form of a 

drug. A major challenge is figuring out 

how to maintain elevated levels of the 

hormone for a substantial period of time, 

a challenge compounded by the hormone’s 

short half-life. 

Despite these challenges, FGF21 therapy 

appears to be a promising approach that 

could have substantial benefits, and Dixit 

and his team is working to turn it into an 

effective therapy. If they are successful, 

aging immune systems in need of rescue 

could—in the not-so-distant future—be 

bailed out by a tiny, life-giving hormone. 


MALINI GANDHI 

MALINI GANDHI is a junior in Morse College majoring in Molecular, Cellular, 

and Developmental Biology. She is interested in immunology, microbiology, 

and evolutionary medicine. 

THE AUTHOR WOULD LIKE TO THANK Dr. Dixit for his time and enthusiasm 

in discussing his work. 


Yang, H et al. (2009) Inhibition of thymic apidogenesis by caloric restriction 

is coupled with reduction in age-related thymic involution. J Immunol 183 (5): 

3040-3052. 


nanotechnology 

FOCUS 

SUNSCREEN THAT BLOCKS MORE THAN SUN 

How a small-but-mighty nanoparticle is revolutionizing sun protection 

BY KENDRICK UMSTATTD // ART BY WASIF ISLAM 

Do you want to go to the beach? This 

question likely brings to mind the 

sound of the waves crashing against 

the shore, the smell of the sea and delicious 

food from beachside vendors, and the cool 

sensation of spreading sunblock across 

your skin. From an early age, it is ingrained 

in our minds that sunscreen is the best way 

to protect against skin cancer. But what if it 

turned out that the same product you use 

to avoid getting skin cancer could actually 

cause damage to the very cells you are trying 

to protect? 

Fortunately, a team of Yale researchers 

has developed a new sunblock formula 

that will block the sun’s rays without generating 

the dangerous byproducts produced 

when applying typical sunscreens. When 

sunlight makes contact with sunscreen, it 

carries excess energy that has to be converted 

into another form. Commercial 

sunscreens sink into the skin, and the solar 

radiation is changed into a form that can be 

dangerous to skin cells. This new sunscreen 

agent, however, binds tightly to the top layer 

of the wearer’s skin, preventing it from 

sinking in. This means that when sunlight 

makes contact with the sunblock, the converted 

energy is given off as harmless heat. 

The secret behind this new sunscreen agent 

is nanoparticles, incredibly small particles 

that in this sunscreen form a stronger barrier 

between your skin cells and the sun’s 

radiation. 

Shining light on the dangers of solar radiation 

Sunlight is made up of a broad range of 

wavelengths. Long-wavelength radiation 

has very little energy and does not risk 

causing skin cancer. UV radiation, on the 

other hand, is composed of shorter wavelengths 

and is therefore very energetic. Because 

UV radiation has so much energy, it 

can act as a genotoxin, meaning that it has 

the ability to alter an organism’s DNA. 

UV radiation causes DNA mutations in 

cells and puts the individual at risk of developing 

cancer. The reason UV radiation 

is most often blamed for skin cancer, as 

opposed to other types of cancer, is because 

sunlight can most easily reach skin 

cells. This risk of developing skin cancer 

is precisely why we apply sunblock before 

going outside for extended periods of time. 

Sunblock serves to literally block your skin 

cells from the DNA-altering properties of 

the sun’s high-energy radiation. 

Dissipating the energy 

The Law of Conservation of 

Energy states that energy cannot 

be created or destroyed, only 

converted from one form to 

another. It is based on this 

principle that the active 

ingredients in current 

sunscreens function by converting solar 

radiation to other forms of energy. If this 

conversion occurs on the skin’s surface, 

the energy is given off as heat. This is a 

harmless process that does not put the 

sunblock wearer at risk. In this scenario, 

sunblock can be compared to a gate that 

prevents any intruders from invading. 

The danger arises when the sunscreen 

sinks into the wearer’s skin cells. Sunscreen 

can be absorbed more deeply into the skin 

when the particles that compose it are 

smaller. Unfortunately, this is often the case 

with more translucent sunscreens, which 

tend to be more aesthetically pleasing than 

opaque, pasty formulas made of larger particles. 

When sunscreen sinks into the skin 

beyond the top layer, reactive oxygen species 


March 2016 


23

FOCUS 

nanotechnology 

IMAGE COURTESY OF KENDRICK UMSTATTD 

(ROS) are formed. These are molecules 

that readily engage in chemical reactions, 

including reactions with DNA. The formation 

of ROS from sunblock’s energy conversion 

can cause damage to cells and the 

DNA that sunblock is meant to protect. In 

this sequence of events, the gate which was 

meant to protect against intruders has been 

broken down. 

Strengthening our defenses 

Michael Girardi, a professor at the Yale 

School of Medicine, was intent on preventing 

the formation of these reactive species. 

Girardi was surprised to see how high the 

levels of ROS formation were when he tested 

commercial sunscreens. “The incidence 

of skin cancer appears to be increasing,” 

Girardi said. He hoped to help address the 

problem by improving the formulation of 

sunscreens. Girardi joined Mark Saltzman 

as part of the Saltzman research group, and 

the two were able to combine the strengths 

of their respective fields of dermatology 

and biomedical engineering to develop an 

improved active sunscreen agent. 

“What makes our sunscreen different 

from those that are currently available 

is its adhesive quality,” said Yang Deng, a 

member of the Saltzman group. Instead of 

sinking into the skin, the sunscreen binds 

to the skin’s surface. Not only does this prevent 

the formation of damaging reactive 

species, but it also comes with comestic 

benefits. Since the substance doesn’t sink 

into the skin, allergic reactions to sunblock 

will be decreased. If you have ever had acne 

or a rash develop after using sunblock, you 

can breathe a sigh of relief, as irritation will 

be lessened with the use of this formula. 

Small but mighty 

You might expect that the particles of 

the team’s sunscreen are very large in order 

to prevent them from sinking into the 

skin. Surprisingly, the particles are not 

only small but are nanoparticles—particles 

which have diameters of about 1/10,000 

of a millimeter. “The particles were engineered 

to bind to the skin with incredible 

adherence while encapsulating the active 

ingredients of sunscreen,” Girardi said. 

When the particles break down, they split 

into safe substances, like lactic acid which 

is produced by one’s muscles during exercise. 

In addition to having safer byproducts, 

the sunscreen developed was found 

to be even better than the typical active ingredients 

in sunscreen at absorbing a broad 

spectrum of UV radiation. 

Beyond providing improved skin protection, 

the formula also has desirable 

aesthetic properties. Unlike current sunscreens, 

this formula is more transparent. 

“It couldn’t be seen with the naked eye. 

That was a pleasant surprise,” Girardi said. 

The fact that the sunscreen has been a success 

in so many regards is a testament to 

the effective collaboration of researchers 

with expertise in varying fields within the 

Saltzman group. As Deng emphasized, the 

whole team worked very closely together to 

advance the research. 

The new sunscreen is also more convenient 

to use. Beachgoers need to reapply 

sunblock multiple times over the course 

of the day to ensure adequate protection. 

The researchers’ sunscreen agent has been 

found to last on the skin for days, only being 

removed when the skin was rubbed 

with a damp towel. The towel removes the 

sunblock agent by helping shed the top layer 

of the wearer’s skin. Although this may 

initially seem like a concern, your body 

actually naturally sheds skin cells. In fact, 

about 20 of your outermost layers of skin 

consist of dead cells. This method of removing 

the sunscreen agent by removing 

dead skin cells highlights Deng’s achievement 

in developing a nanoparticle that 

binds very strongly to the wearer’s skin. 

As opposed to having only one goal in 

mind for the future of this research, the 

Saltzman research group has decided that 

the sky is the limit. In regards to the sunscreen 

formula, the team wants to develop 

a method of applying it in a lotion or cream 

form that only has to be applied once a day. 

Beyond sunblock, the team has other ideas 

that could positively impact different areas 

of a consumer’s daily life. “We’ve come up 

with literally over 50 different potential 

ways that we might be able to use the same 

nanotechnology platform,” Girardi said. 

Should I throw out my sunblock? 

An emphatic no. The group still has further 

tests to conduct, and while you may be 

applying sunscreen designed by the Saltzman 

research group in the near future, you 

will not find it on the shelves quite yet. In 

the meantime, do not take a vow to stop using 

sunscreen, as the benefits far outweigh 

any potential downsides. “The last thing I 

want is people to stop using sunscreen and, 

[as a result], suffer from more damage,” Girardi 

said. It looks like sunblock will continue 

to be a fundamental part of a trip to 

the beach. 


KENDRICK UMSTATTD 

KENDRICK UMSTATTD is a freshman Electrical Engineering and Computer 

Science major in Berkeley College. She is a Copy Editor for the Yale Scientific 

Magazine and works as a research assistant in Yale’s Social Robotics Lab. 

THE AUTHOR WOULD LIKE TO THANK the Saltzman Research Group for 

their commitment to advancing research in skin protection, with a special 

thanks to Dr. Mark Saltzman, Dr. Michael Girardi, and Dr. Yang Deng for their 

time and enthusiasm. 


Gruijl, F.R. De. “Skin Cancer and Solar UV Radiation.” European Journal of 

Cancer 35, no. 14 (November 1, 1999): 2003-009. Accessed February 5, 2016. 


environmental science 

FEATURE 

GOING GREEN 

Giant icebergs cause phytoplankton blooms 

►BY ELLIE HANDLER 

IMAGE COURTESY OF WIKIPEDIA 

Giant icebergs are over 11 miles in length and only form in 

the Southern Ocean. Their huge size has made them difficult 

to study. 

Sunlight streams through the water as microscopic plants 

cover the ocean’s blue depths with a thin film of vibrant green. 

Some ride the ocean currents, completely at the mercy of the 

waves, while others propel themselves with long tail like structures 

called flagellum. The world’s oceans teem with phytoplankton, 

these tiny single celled plants, but they do not thrive 

equally well in all oceanic areas. Phytoplankton growth is limited 

by the concentrations of minerals and nutrients. When 

enough resources are present, phytoplankton growth explodes 

and forms a bloom, a drastic increase in population size. 

Blooms are visible to the naked eye, coloring patches of water 

with green chlorophyll, a molecule that allows plants to convert 

carbon dioxide into sugars and oxygen by using energy from 

the sun. 

Icebergs melt as they travel through oceans, slowly releasing 

the nutrients trapped within the ice to create the ideal conditions 

for phytoplankton blooms. A new study from Sheffield 

University discovered that the blooms trailing behind giant icebergs—defined 

as over 11 miles across—last longer and extend 

significantly farther than those from average sized icebergs. 

These blooms participate substantially in carbon sequestration: 

the capture and storage of atmospheric carbon. When the phytoplankton 

die, their bodies sink down to the sea floor, returning 

carbon to the earth. 

Grant Bigg, a professor of earth systems science at Sheffield 

University, led the study. His team of researchers examined photos 

of the Southern Ocean, measuring changes in ocean color 

to estimate the concentration of chlorophyll near giant icebergs. 

Since chlorophyll is a biomolecule within phytoplankton, the 

spread of high concentrations of it correlates with large blooms. 

As anticipated, the researchers discovered that phytoplankton 

flourished near icebergs, but they were surprised by the size 

of the blooms. The chlorophyll trails were massive, measuring 

three to four times the length of the giant icebergs on average. 

Some icebergs even had plumes as long as 10 times their length. 

To put that in context, previous studies recorded phytoplankton 

trails that were approximately equal to the length of the icebergs. 

These studies only monitored small icebergs, however. 

Previous studies monitoring chlorophyll did not look at giant 

icebergs because they are difficult to survey. Since giant icebergs 

have the same material composition as smaller icebergs, 

they were expected to affect phytoplankton blooms similarly. 

But larger amounts of fresh water melt off giant icebergs, increasing 

mineral concentrations and phytoplankton activity. 

The effects last longer, even as the iceberg travels away, because 

the nutrients are consumed slowly. Discovering these differences 

between giant and average-sized icebergs changes our perspective 

on carbon sequestration, since smaller icebergs do not 

contribute significantly to the storage of carbon. 

Giant icebergs are incredibly rare, with only a couple dozen 

floating in the Southern Ocean at a time. Smaller icebergs are 

formed by calving events, the splitting of glacier ice at the edge 

of an ice shelf. But giant icebergs form by a different mechanism; 

they break off when something integral to the ice sheet 

is disturbed. Giant icebergs can only arise from large ice sheets, 

exclusively located around Antarctica. Northern oceans do not 

have these huge sheets of ice, so giant icebergs are not found in 

the northern hemisphere. Even in the Southern Ocean, their 

numbers are limited. “The loss of really large ones happens really 

rarely. Some regions might not get a large one released for 

ten years,” Bigg said. 

This study uncovered an important carbon sink, a location 

that absorbs more carbon from the atmosphere than it releases. 

Terrestrial organisms consume approximately half of the 

earth’s carbon, but the remaining amounts are absorbed into 

the ocean. Approximately half of the carbon absorbed into 

the ocean is taken up through the dissolution of carbon dioxide 

into cold seawater while the remaining portion is absorbed 

by phytoplankton and seaweed growth. The Southern 

Ocean alone takes up approximately 10-15% of the carbon absorbed 

annually. Increased carbon absorption by phytoplankton 

near giant icebergs likely accounts for 2-3% of the global 

carbon sink. While this amount may seem insignificant, Bigg 

explained that this process is crucial to remove carbon from the 

climate system. “It’s a relatively small amount, but everything 

adds to the total,” Bigg said. Additionally, this mechanism acts 

as a negative feedback loop for global warming. With the onset 

of climate change, more giant icebergs are expected to form, 

but their presence could help to slow down the increase of atmospheric 

carbon. 


March 2016 


25

FEATURE 

biomedical engineering 

A BRAINY VANISHING ACT 

New bioresorbable technology improves brain monitoring 

►BY MAHIR RAHMAN 

POW! You fall to the ground. Bystanders call 911. EMTs transport 

you to the hospital. Your breaths are irregular, your pulse is 

slow, yet your heart pumps as much blood as it can with every 

beat. Your symptoms meet the telltale signs of increased intracranial 

pressure—a buildup of pressure inside the skull—from traumatic 

brain injury (TBI). Your doctors decide to perform neurosurgery 

to alleviate the pressure. However, neurosurgery can lead 

to swelling that also increases your intracranial pressure, throwing 

the brain’s continuous checks and balances off rhythm and leading 

to potential brain damage. Following surgery, how can doctors 

make sure your brain sticks to the beat? 

“Intracranial pressure monitoring is the mainstay of how we 

manage some of these [TBI] patients early on,” said Wilson Ray, 

assistant professor of neurological and orthopedic surgery at the 

Washington University School of Medicine in St. Louis. Ray and 

John Rogers, professor of materials science and engineering at the 

University of Illinois at Urbana-Champaign, teamed up to develop 

bioresorbable devices to monitor brain conditions like intracranial 

pressure. 

“The devices themselves are made out of several types of materials, 

configured in a multi-layer stack to provide the kind of functionality 

we need,” Rogers said. The devices have two main components: 

a sensor and an electrode system. The sensor is placed 

within the brain, resting on a pen-tip-sized base. Wires connect it 

to the electrode system—a dime-sized electric circuit placed between 

the skin and the skull—that stores information in a nearfield 

communication (NFC) chip. Excluding the chip, all these 

materials are biodegradable, breaking down through natural processes 

like banana peels. The device uses the biodegradable chemical 

PLGA as a protective coating to lengthen its lifetime. Placed 

underneath the sensor to form an air cavity, a membrane made of 

PLGA also bends in response to environmental changes to help 

the sensor measure conditions accurately. After the materials biodegrade, 

bodily fluids like blood can absorb and remove the byproducts 

from the body, making the device bioresorbable. 

Depending on the type of sensor, the device can measure pressure, 

temperature, or flow rates among other conditions specific 

to the sensor’s location. The sensor converts the condition information 

into electricity that flows through the wires for the electrode 

system to process. The NFC chip exchanges information on 

internal conditions only when an external reader hovers within 

25 millimeters of the chip’s location underneath skin. The same 

technology powering Apple Pay and Google Wallet may soon advance 

health monitoring. 

However, the devices have not entered hospitals yet. Ray and 

Rogers conducted the first round of device testing in artificial 

cerebral spinal fluid (CSF) and rats. CSF is the clear, colorless, 

shock-absorbing liquid that helps our brains stay afloat inside 

our skulls and flushes away the waste produced by our brains 

throughout the day. Observing that the device dissolved completely 

in artificial CSF, the researchers predicted that the body 

would naturally wash out its byproducts. “The body tries its best 

to remove foreign bodies from [itself],” said Rory Murphy, a chief 

resident in neurosurgery at the Washington University School of 

Medicine in St. Louis. The researchers studied test implants in rats 

to ensure that the dissolved byproducts were treated as welcomed 

guests rather than foreign invaders. Otherwise, an immune response 

would have signaled the body’s security forces to attack. 

Fortunately, rat brains were very hospitable. 

Current monitoring implants do not receive the same welcome. 

They do not biodegrade, they act as platforms for infection while 

they remain in the body, and they outlast their brief period of clinical 

use. “That first 24, 48, and certainly 72 hours is where you are 

making some of those critical decisions regarding on-going medical 

management versus surgical intervention,” Ray said. Although 

current implants do provide accurate condition information following 

TBI or surgery, doctors must perform additional surgery 

to remove them. While preventing a potential immune response, 

this creates yet another opening for health complications. 

In rats, the new bioresorbable devices matched the accuracy of 

current monitoring implants without the associated side effects. 

Nevertheless, Murphy stresses further testing must be done to 

guarantee that the devices are completely safe for use in humans. 

If proven safe, researchers could convert the monitoring device 

into a medication. “We have approaches to do that,” Rogers said. 

He believes the device could be modified to electrically stimulate 

a specific brain area, allowing clinicians to provide electrotherapy 

remotely. Likewise, the electrodes could be programmed 

to release prepackaged drugs. “There is going to be tremendous 

opportunity as to which direction [device applications] will go,” 

Ray said. 

IMAGE COURTESY OF JOHN ROGERS, UNIVERSITY OF ILLINOIS 

►Barely the size of a grain of rice, this bioresorbable sensor 

can measure brain conditions when needed and then disappear. 


materials science 

FEATURE 

A STICKY IDEA 

Yale researchers investigate new models of adhesives 

►BY CHUNYANG DING 

Stick your hand into a tub of electric blue Play-Doh, and 

the rubbery clay gives way immediately, conforming to your 

fingers. As you lift out your hand, some of the moldable fun 

might still cling on! Believe it or not, the stickiness of Play- 

Doh is a close analogy to how the science of adhesion works. 

Sticky materials surround us; they are literally the glues holding 

everything together. They are in everyday products like 

Post-It notes, but they also guide science as diverse as the development 

of advanced glues and the biophysics of how cancer 

cells spread. Recently, a research collaboration led by Yale 

professor Eric Dufresne discovered a new kind of interaction 

between adhesive materials, paving the way for developing 

smarter sticky materials. 

The concept of stickiness has been around for centuries, 

since early civilizations began repairing pottery with sticky 

tree resin. However, understanding why adhesives work took 

much longer. Even the creation of the Post-it note was an accident—its 

inventor was actually trying to create a strong glue. 

While those ubiquitous sticky notes arose from a fortunate 

accident, manufacturers needed a better understanding of the 

underlying science to develop serious adhesives. 

In the 20th century, researchers began to quantify the 

strength of sticky materials and come up with theories for 

why adhesion occurs. The most prominent model emerged 

in 1971, when researchers at Cambridge began to think of 

stickiness at the atomic level. Their idea was that all materials 

are deformable, so when two objects push against each other, 

both change their shape to a certain extent. This model can be 

thought of like the Play-Doh molding to your hand—if you 

only lightly pat the material, it does not have a chance to deform 

because the area of contact is too small. But when you 

really push into the Play-Doh, it spreads itself around your 

fingers, increasing the surface area of contact. Increased surface 

contact causes a larger frictional force, leading to stickiness. 

This model dealt with a maximum of three different surfaces 

touching each other at a time: the two objects in contact 

and the surrounding air. While the model is logical, it has 

not worked well for advanced gel-like adhesives because these 

gels leak liquids, providing a new point of contact between the 

sticky materials. 

Katharine Jensen, researcher at the Yale’s Soft Materials 

Lab, conducted a careful experiment exploring new causes of 

stickiness. Her team prepared two types of adhesive gels: one 

with liquid components and one without them. The researchers 

looked at how the gels stuck to solid objects at a micrometer 

scale, finding that water escaped from liquid adhesive gels 

as they deformed, similar to sponges. Liquid molecules have 

many different properties from solids, such as their ability to 

stick to each other by the property of surface tension. Therefore, 

the liquid component of certain materials changes the 

way that scientists calculate their stickiness. 

But why is this discovery important? The old model works 

for many common adhesives, but the new research helps scientists 

better understand the stickiness of certain biological 

processes, like cancer cell mobility. Mutations in cancer cells 

transform the protein structure of their cell walls, leading to 

more deformable cell walls. Surprisingly, this causes cancerous 

cells to be more mobile than normal cells, allowing cancer 

to spread throughout the body more easily. This model seems 

to contradict past models of adhesion, since deformability 

typically increases stickiness. However, the new research may 

provide an explanation for why more deformability can lead 

to increased metastasis, the spread of cancer. The process of 

metastasis is complex, but these differences in adhesive properties 

are important to understand, as they may help researchers 

develop better detection methods for metastatic cancers. 

To be clear, this discovery does not contradict past theories 

of adhesion. Instead, it improves on the old model in an 

unprecedented way. Most adhesives do not leak water when 

squeezed, so the previous model is still a great approximation. 

The new theory also makes intuitive sense. “I’ve had a 

lot of people in the field say ‘I never would have thought it 

would have done that, but now that you’ve shown it, of course 

it does,’” Jensen told the Yale School of Engineering and Applied 

Sciences. 

There are many potential uses for this new model, from improving 

regular synthetic adhesives to designing new types of 

gels. A particularly interesting development is in tissue engineering, 

as scientists seek to grow tissues for patients in need. 

Researchers currently use hydrogels as the template for growing 

tissues, as the cells stick to the gels to grow in the right 

shape. However, if the adhesion between the hydrogel and the 

cell is not exactly right, the produced organ could be a dud. 

This newly developed model could better tune the gel to the 

cell, reducing the number of duds produced. 

Improved adhesives may soon surround us, but if they work 

properly, their presence will be undetected. They are the silent 

heroes holding our lives together. Improving our models of 

stickiness will guide the development of better adhesives, but 

perhaps the most significant takeaway from this study is how 

it exemplifies the incremental nature of scientific research. Instead 

of overturning previous models, new research improves 

our knowledge of the world bit by bit. Maybe that is the “stickiest” 

idea of all—science depends on steady research, improving 

old models in an ongoing search for truth. 


March 2016 


27

FEATURE 

pharmacology 

THE 

EXOSOME 

BATTLING CANCER WITH OUR 

BODY’S OWN TROJAN HORSE 

by Cheryl Mai | art by Alexander Allen 

You may have never heard of the anti-cancer 

drug paclitaxel, but it is indispensable to our 

modern healthcare system. It sits on the World 

Health Organization’s List of Essential Medicines, 

and its annual sales surpassed one billion 

dollars in 2000. It has saved countless lives since 

its discovery in 1967. Yet the drug is also incredibly 

toxic, causing a low blood cell count, hair 

loss, nausea, and joint and muscle pain. Its extensive 

list of side effects is representative of an 

ongoing challenge in chemotherapy: striking a 

balance between destroying cancer cells and protecting 

the patient’s noncancerous cells. 

Paclitaxel binds to molecular motors in cells, 

thus inhibiting cancer cell growth, but it also prevents 

the division of non-cancerous cells. So how 

can cancer drugs be administered in small doses 

that efficiently and specifically target tumors? 

Researchers at the University of North Carolina 

have proposed a solution that utilizes small 

cellular bubbles—called exosomes—naturally 

found in our tissues. In the study, Elena Batrakova 

and her team extracted exosomes from immune 

cells and loaded paclitaxel into these vesicles. 

Historically, drug resistance in cancer cells 

has been difficult to overcome, but using exosomes 

to deliver paclitaxel dramatically increased cytotoxicity in 

drug resistant cells and decreased tumor growth in mice. The increased 

effectiveness of this delivery system could allow healthcare 

providers to administer lower doses, alleviating the severity 

of side effects associated with cancer treatment. 

Exosomes, the stars of this study, are easy to miss, measuring 

a mere 100 nm in diameter. “We knew practically nothing about 

exosomes 10 years ago,” said Philip Askenase, professor of Medicine 

and Immunology at the Yale School of Medicine. In recent 

years, our knowledge of exosome origin and function has expanded. 

Secreted by most cells, these small vesicles are thought 

to be involved in cell-to-cell communication and the carrying of 

RNA and protein cargos. 

While our knowledge is still limited, researchers are already engineering 

methods to use exosomes as vehicles for drug delivery. 

One such study successfully released therapeutics for Parkinson’s 

disease into cellular targets using exosomes. Perhaps the most attractive 

feature of this delivery system stems from its natural origin. 

Our immune systems can distinguish between self and nonself 

molecules and launch attacks on foreign invaders. Although 

beneficial, this ability sometimes disrupts medical procedures; 

for example, it can lead to organ transplant rejection. However, 

since exosomes are naturally derived, they are shielded from immune 

system attacks by an “invisibility cloak.” Synthetic vehicles, 

on the other hand, are recognized by the immune system as nonself 

and rapidly cleared away. 

Batrakova and her team recognized how useful these natural 

vehicles could be to cancer drug delivery. Due to the high toxicity 

of chemotherapy, decreased doses are often advantageous. For 

instance, paclitaxel functions by targeting tubulin, a motor protein 

found in all cells, and stopping it from disassembling. Since 

tubulin assembly and disassembly are necessary for chromosome 


pharmacology 

FEATURE 

movement during cell division, paclitaxel effectively halts mitosis, 

the process by which cells split in two. While bad for cancer 

cells, which normally proliferate at high rates, paclitaxel also 

stops mitosis in non-cancerous cells. This is partially why hair 

loss is a common side effect of chemotherapy. Yet, by specifically 

targeting tumors and protecting the drug from the immune system, 

the exosome acts as an excellent candidate for efficient drug 

delivery. When delivered by this system, a significantly decreased 

dosage of paclitaxel 50 times lower is still effective, reducing the 

risk of systemic toxicity associated with larger doses. “This is a 

way to send a ‘hand grenade’ in highly concentrated form into the 

enemies—cancer cells,” Askenase said. 

In the study, Batrakova’s team harvested exosomes from macrophages, 

a type of white blood cell. Afterwards, they tested different 

methods for loading paclitaxel into the vesicles. Sonication, 

the act of using sound energy to agitate the exosome membranes, 

was the most effective. As the 

membranes became more fluid, large 

amounts of paclitaxel were incorporated 

into the exosomes. 

Subsequently, Batrakova compared 

the performance of exosomes to other 

drug delivery systems, such as frequently 

used nanocarriers, liposomes, 

and polystyrene nanoparticles. To 

compare these systems, the lab tagged 

each carrier with a fluorescent label 

and visualized its location under a 

microscope. Compared to other drug 

carriers, exosomes accumulated at 

higher concentrations inside cancer 

cells. 

Further experiments showed that 

exosomes can bypass the defensive 

mechanisms of drug-resistant cancer 

cells. Resistant cancer cells carry 

transporters on their outer membranes 

that pump drug particles out 

of the cell before they can induce cell 

death. Exosomes dodge these transporters: 

“Since exosomes have adhesive 

proteins on their surfaces, they 

stick to the side of cells like Velcro,” 

Batrakova said. She believes that these 

adhesive interactions allow exosomes 

to fuse with cancer cell membranes, 

avoiding interactions with the membrane 

transporters. Other drug carriers 

release their cargo into the fluid 

surrounding cancer cells, making it 

more difficult for the drug particles to 

dodge these defensive mechanisms. 

To validate their findings, Batrakova’s team used models of lung 

cancer in mice. After treatment with paclitaxel-containing exosomes, 

the number of cancer cells in the mice’s lungs dropped 

significantly. These results have important implications for the 

future of cancer treatment. The efficacy of exosome-mediated delivery 

may decrease the necessary doses of chemotherapeutics, 

minimizing unwanted side effects. Furthermore, exosomes may 

provide a method for overcoming drug resistance in cancer cells. 

At the same time, Batrakova acknowledges that many questions 

still remain unanswered. “The biggest surprise was when exosomes 

did not target healthy tissues,” she said. This observation 

cannot yet be explained, but she remains hopeful that successive 

experiments will provide more clues about the mechanisms of 

exosomes, not only in cancer, but also in other diseases. “The implications 

can be very wide,” Batrakova said. 


March 2016 


29

FEATURE 

chemical engineering 

LITHIUM ION 

BATTERIES 

TAKE THE HEAT 

new self-regulating batteries switch off when overheated 

BY EVALINE XIE // ART BY AYDIN AKYOL 

Batteries are found in everything from cell phones to cars, 

quietly powering our everyday existence. With rising pressures 

to find more renewable sources of energy, batteries hold immense 

potential to do even more—for example, to store the excess 

energy from solar cells and wind turbines to release when 

demand is high, or to fuel efficient and easily-rechargeable electric 

vehicles. However, news reports and recalls on consumer 

products have revealed the potential danger beneath these batteries’ 

noiseless exteriors: overheating laptops, vehicles catching 

fire, and hoverboards exploding underneath people’s feet. The 

primary culprit for these hazards is a buildup of heat in lithium 

ion batteries, which are high in energy density, inherently 

reactive, and easily short-circuited. If a battery’s temperature 

exceeds approximately 150 degrees Celsius, it can catch fire and 

cause an explosion. 

Earlier in January, Zheng Chen, Yi Cui, and Zhenan Bao of 

Stanford published their work on a new technology to solve this 

problem in lithium-ion batteries. Using a polymer material embedded 

with nickel nanoparticles with spiky surface features, 

they invented a self-regulating film that can shut down batteries 

in case of overheating and short-circuiting. “Our inspiration 

[was] to solve the general safety issues related to batteries,” said 

Chen, the lead author of the paper. “It could be small scale or 

large scale batteries in different formats; all are subject to safety 

issues.” 

To understand the mechanism for these self-regulating batteries, 

a basic understanding of the hazards of traditional lithium 

ion batteries is necessary. Why exactly do lithium ion batteries 

catch fire? Despite their reputation, standard lithium batteries 

are, for the most part, reliable. They are commonly 

used due to their high energy, power density, and reliability, 

but they can also be dangerous if the batteries 

become damaged. In a functioning battery, lithium 

ions flow in a balanced circuit from an oxide cathode, 

to an electrolyte solution of lithium salts and 

organic solvents, then to a carbon anode. Damage 

to the thin barriers separating the cathode and anode, 

however, can create an internal short-circuit. 

When short-circuited, overcharged, or otherwise 

misused, the batteries can reach dangerously high 

temperatures, leading to “thermal runaway”—a series 

of chemical reactions that raise internal temperature 

and pressure until the battery bursts into 

flames. 

To combat this issue, the researchers devised a system 

to decrease the conductivity of electrodes at high 

temperatures. In a previous project, Professor Bao had 

created a device that monitored body temperature, so the 

team fabricated a similar material for batteries. 

They encountered new difficulties, however, since the battery 

film quickly degraded when exposed to the chemicals 

inside batteries. To prevent degradation, the team coated the 

nickel particles with conductive graphene, a thin layer of carbon 

atoms. “The nickel provides the composite with electrical 

conductivity, the graphene coating layer on the nickel surface 

provides them electrochemical stability, and the polyethylene 

is the matrix to hold such particles and can expand and shrink 

depending on increasing or decreasing temperature,” Chen said. 


chemical engineering 

FEATURE 

When attached to battery electrodes, the particles in the 

film conduct electricity. But when the battery heats up above 

a certain temperature, thermal expansion causes the plastic to 

stretch. As a result, the particles in the film spread apart, halting 

electric current and shutting off the battery. This process occurs 

remarkably quickly, with conductivity dropping by a factor of 

107-108 in a mere second. After the film cools, resistance decreases 

and the film relaxes, allowing electron flow to continue. 

Consequently, the thermal switching of the batteries is quick 

and reversible. 

This is not the first project that attempted to eradicate 

the dangers of overheating batteries. In an earlier 

design, Cui created a lithium-ion battery with an “early-warning 

system” to detect abnormal operating conditions. 

Cui and his colleagues decided to build a “smart separator” 

of copper between the anode and cathode of the battery. By 

sensing the voltage difference between the anode and cathode, 

the copper could recognize abnormal conditions to determine 

when the battery should be removed to prevent short-circuiting. 

Elsewhere, at the University of Rhode Island, Ronald Dunn has 

experimented with including flame-retardants in lithium-ion 

batteries. 

So how is this new design different? In previous designs of 

safe batteries, the mechanisms for shutting off overheating batteries 

were irreversible; the batteries 

could not be used after 

overheating. The reversibility 

of thermal 

switching is truly 

innovative. 

When the 

researchers repeatedly 

heated their battery with a 

hot-air gun, the film was very resistant 

to high temperatures and 

still reliably conductive after twenty 

cycles of being switched on and off. 

Can this polyethylene film eventually 

be implemented on a larger 

scale? Chen thinks so. “Both the 

components and fabrication process 

are low cost, so we don’t think 

there will be a problem for scaling 

up,” Chen explained. Until then, he 

and the other researchers hope to continue 

with their research to improve the 

batteries further, decreasing the overall 

thickness of the composite film and increasing 

its conductivity at room temperature. 

“We still need to improve our materials 

design and processing,” Chen said. 

If a self-regulating, temperature selective material 

was used in batteries, it could potentially maintain 

good battery performance at normal temperatures, 

but more importantly, it could provide a reusable safety 

mechanism to shut down at high temperatures. This new 

technology may decrease the risks associated with our smartphones, 

laptops, and electric cars. And perhaps even hoverboards 

may return to the Yale campus. 


March 2016 


31

FEATURE 

neuroscience 

Sniffing Out Alzheimer’s 

By Christine Xu 

Art By Wasif Islam 

A 

few years ago, a media sensation erupted over the discovery 

that some dogs can detect the scent of cancer in humans. 

Now, for the first time, researchers have shown that it may 

be possible to “sniff out” Alzheimer’s disease in a similar way— 

specifically, by examining odor changes in urine at the onset of 

Alzheimer’s. 

A recent study by the Monell Chemical Senses Center, the U.S. 

Department of Agriculture, and Case Western Reserve University 

investigated the fluctuations in urinary chemicals that accompany 

the early stages of Alzheimer’s disease. Alzheimer’s is a form of 

dementia that drastically impairs memory and cognition, affecting 

approximately 5.1 million Americans over the age of 65. Despite 

ongoing research efforts, the causes of Alzheimer’s are unclear 

and effective treatments are nonexistent. This study explored 

the biochemical changes associated with the progression of 

Alzheimer’s, revealing possible new routes to improving diagnostics 

and treatments. 

In the study, the researchers utilized three mouse strains that 

modeled human Alzheimer’s disease by genetic overexpression 

of the amyloid precursor protein gene (APP). By searching for 

differences in physiology between the APP Alzheimer’s mouse 

models and littermate control mice, the researchers discovered 

that the concentrations of certain volatile chemicals were altered 

in the urine of the Alzheimer’s mice. These differences may reflect 

underlying changes in the body’s metabolism. 

“This is a proof-of-concept study that shows that Alzheimer’s 

mouse models possess a distinct urinary chemical profile from 

mice that don’t harbor the mutation,” said Daniel Wesson, assistant 

professor of neuroscience at Case Western Reserve University and 

contributing author. 

He explained that these observations in mice could have direct 

implications for our understanding of Alzheimer’s disease in 

humans: “There is the possibility that urinary chemical differences 

in humans with Alzheimer’s could be useful in early detection of 

the disease.” In short, the smell of a patient’s urine could be a novel 

diagnostic tool for Alzheimer’s. 

Wesson added that research on olfaction, the sense of smell, 

has often contributed to our understanding of disease. Wesson’s 

lab studies the mammalian olfactory system, focusing on the 

intersection between Alzheimer’s and olfaction. In addition to this 

study on urinary odors, his lab has also investigated the neurological 

basis for the defects in the sense of smell in Alzheimer’s patients. 

Justus Verhagen, a Yale professor and neuroscientist at the John B. 

Pierce Laboratory, believes that olfaction has not received adequate 

scientific attention. “The sense of smell is absolutely undervalued 

both scientifically and clinically. Specifically, the sense of smell is 

underused in Alzheimer’s research—both in terms of changes in 

the patient’s ability to smell, and changes in the patient’s own odors 

due to the disease.” 

Verhagen pointed to the relatively well-known example of dogs 

trained to sniff out the earliest signs of cancer. “If we could do the 

same thing for Alzheimer’s, by training animals to pick up the 


neuroscience 

FEATURE 

different smells of patients versus non-patients, we would have 

an additional diagnostic tool besides brain imaging and cognitive 

testing,” he said. 

In fact, Wesson said that he was partly inspired by the earlier 

findings that animals can detect cancer. Previous research in 

this area fascinated him: “Groups around the world have been 

training animals to detect the smell of cancer in T-shirts and skin 

samples, and so on. Some literature even suggests that transient 

biological events—including seizures and glucose levels—can 

cause significant odor differences in both the urine and the body. 

Knowing about this was definitely one of the motivations for our 

project.” 

Still, the results of this study cannot yet be translated into a 

feasible diagnostic for Alzheimer’s, as several limitations highlight 

the necessity of continued research. Wesson noted that, while 

mice are valuable models for human conditions, mouse and 

human metabolism are drastically different. The changes in urine 

discovered in mice may be dissimilar to changes in a human patient. 

Moreover, since a mouse has a lifespan of only two and a half years, 

the disease must follow a condensed trajectory of pathogenesis in 

mice. 

“The mice are partial models, and while they can be powerful, 

it’s difficult to recapitulate an incredibly complex human disorder 

in a mouse,” said Wesson. Thus, continued research and testing 

with human subjects is necessary before the results of this study 

are applicable for Alzheimer’s patients. 

Additionally, the researchers do not fully understand why certain 

chemical concentrations in the urine fluctuate in response to 

pathogenesis. They have, however, documented the precise changes 

to understand that exactly sixteen chemical components change in 

concentration. All of these components were already present in the 

urine, suggesting that the development of Alzheimer’s does not lead 

to the addition or deletion of a chemical in the urine. However, the 

biochemical basis for this phenomenon remains hazy. 

“It would be unfounded speculation to try and say exactly why 

one of these molecules changed in concentration at this point,” said 

Wesson. “That would require careful biochemical work.” 

Despite the limitations of the study, its preliminary results hold 

enormous potential for scientific and medical discoveries. The 

study provides insights into the genetic, cellular, and molecular 

factors that contribute to the onset and progression of Alzheimer’s. 

“Basic biological research is very important. We hope to uncover 

insights that open doors in ways that we can’t even imagine, doors 

that lead to diagnostics, treatments, and maybe even a cure,” 

Wesson emphasized. 

Urinary biomarkers could become not only a new diagnostic 

tool for early stage Alzheimer’s, but also a valuable research tool 

for scientists studying the disease. A robust understanding of the 

biochemical factors behind Alzheimer’s disease could provide 

a more sensitive methodology for researchers. For instance, in 

a future clinical study testing a potential cure for Alzheimer’s, 

researchers could use urinary chemical profiles to monitor disease 

progression in test subjects or detect subtle improvements in 

condition. 

This study has paved the way for advances in treating a 

prevalent and disastrous disease. “It’s a huge public health issue. 

It’s important that we continue to discuss this kind of research, 

since the possibilities at this stage are still unknown to anyone,” 

said Wesson. The research is gaining well-deserved attention: 

“This is an original and exciting study. Looking at the differences 

in urinary compounds, researchers are asking, ‘How can we relate 

these changes back to abnormalities in metabolism and genetics? 

What could underlie these changes? What does it mean?’ We need 

to keep asking these questions,” stated Yale Professor Verhagen. 

IMAGE COURTESY OF THE WESSON LABORATORY 

►Olfaction, or the sense of smell, is a major focus of both Wesson’s and Verhagen’s studies. Olfactometers, such as the homemade machine 

in Wesson’s laboratory, are valuable tools in the study of the olfactory system. 


March 2016 


33

I 

DEBUNK NG 

SC ENCE 

HUMAN 

MICROBIOTA 

►BY CAROLINE AYINON 

The human digestive tract is a thriving ecosystem, teeming with 

life and activity. On an intellectual level, many of us know this, even 

if it can be discomfiting to think about the trillions of living cells 

in our guts that constantly work to transmute food into energy. 

Perhaps more unsettling is an oft-repeated bit of trivia: the bacteria 

inside of us outnumber our own human cells ten to one. However, 

new research conducted by Ron Milo, Shai Fuchs, and Ron Sender 

at the Weizmann Institute of Science has recently proven that this 

long-standing myth is false, and the ratio is actually closer to 1 to 1. 

The 10 to 1 myth originated from a 1972 approximation by 

microbiologist Thomas Luckey, who used rough estimates on the 

make-up of human intestines to determine the ratio. He calculated 

that one gram of intestinal matter contained 100 billion microbes 

and assumed that an average human had 1000 grams of intestinal 

matter. Using these numbers, he estimated that 100 trillion microbes 

thrive in the human body. Luckey cited no evidence for his data— 

and probably did not anticipate how often it would be cited—but in 

1976, scientists further publicized his estimate by comparing it to 

the approximated 10 trillion cells in the human body, creating the 

ten to one ratio students are now taught today. 

Milo’s team revisited the available literature in order to revise the 

current estimate. “We share a fascination with numbers in biology,” 

said Milo. “We believe that getting the numbers right provides 

a profound understanding of the system one is trying to study.” 

Looking at some of the quantitative assumptions we make about our 

body allows us to better characterize its functions and capabilities. 

In reviewing the methodologies previously used by researchers, 

the team found a major error in Luckey’s 1972 calculation: he 

overestimated the number of bacteria present in the gut by falsely 

assuming that bacteria reside throughout the entire alimentary 

canal. In reality, bacteria reside primarily in the colon to assist in 

its numerous digestive functions. After adjusting for this fact, Milo 

and his team altered the previous estimate from 1014 bacterial cells 

to approximately 4x1013 bacteria within our bodies. Milo also 

calculated an increased number of total human cells, resulting in a 

revised ratio of approximately one to one. 

As with most biomedical estimates, Milo’s calculations rely on a 

reference human body but do, nevertheless, account for variations 

between people of different sizes and genders. For example, total 

blood volume is lower in females than in males—as is the red blood 

cell concentration—and both factors affect bacteria count. Milo’s 

team repeated their calculations for women and infants, also taking 

into account factors such as obesity. The obtained values were within 

two fold of the standard 1.3:1 ratio. 

Regardless, these minute differences between individuals do not 

detract from the implications of Milo’s study. These new findings 

drastically differ from the previously commonly accepted ratio. In 

fact, Milo claims that his newly developed ratio is so close to one, 

that it could be reversed by a single defecation, causing human cells 

to outnumber bacterial cells for several hours. Such variation may 

also occur due to routine medical procedures affecting the colon, a 

possibility that was not explored with the previously erroneous 10 

to 1 hypothesis. 

It is important to note that the reduced estimate does not diminish 

the established biological importance of microbes in our bodies. 

In fact, it might help researchers look beyond cell count number. 

“I think it will help focus the motivation of microbiome studies on 

the many great reasons for studying [bacteria’s] effects,” said Milo. 

Bacteria play crucial roles in immune system regulation, food 

digestion, and nutrient production. It is also likely that bacteria 

employ more genes and produce a wider range of chemicals than 

our own cells in ways that are beneficial to our system. 

Nevertheless, these improved approximations highlight the 

inevitable possibility of error in scientific calculations and pave 

the way for further investigations of the human microbiome. For 

example, most of our assumptions about bacteria in the gut stem 

from the analysis of bacteria found in feces. However, Milo questions 

how different the density of internal bacteria might be. “This is just 

one example of an open question that is highlighted now because we 

want to get the best quantitative answer,” he said. Investigations into 

this and other quantitative problems, such as the number of viruses 

found in the human body or the number of synapses in the brain, 

may place into question many facts about our species currently 

taken for granted. 

More information on how numerical methods can answer 

biological questions can be found freely in the ebook Cell Biology 

by the Numbers by Milo and his colleague Rob Phillips, professor of 

biophysics and biology at Caltech. 

IMAGE COURTESY OF NATIONAL INSTITUTE OF HEALTH 

►Bacterial cells have been found to slightly outnumber human cells 

in the body by a ratio of 1.3:1. 


BLAST 

from 

the 

PAST 

Foregone Forensics: A Brief History of Crime-Solving 

►BY ISABEL WOLFE 

It is 1984. Your name is Alec Jeffreys, and you are studying 

sequences of repetitive DNA in the human genome. 

You find patterns within these sequences that are hereditary 

but highly variable between individuals. Before long, 

you discover the potential to identify a person using these 

distinctive patterns within DNA. This technique, called 

DNA fingerprinting, compares the DNA in a person’s cells 

to biological matter from the scene of a crime. Fast forward 

30 years, your game-changing discovery has helped 

convict criminals, exonerate the innocent, and identify 

countless victims. 

The first forensics textbook was produced in the 15th 

century, and in the 1540’s, French doctor Ambroise Paré 

laid the foundations for modern forensic pathology by 

studying trauma on human organs. One of the first documented 

uses of physical matching occurred in 1609, when 

an Englishman was convicted of murder because a piece 

of newspaper in his pocket matched the wadded paper in 

a pistol. By the 19th century, sufficient scientific advances 

including fingerprint classification, toxicology assays, and 

trace evidence analysis had been made to spark a forensic 

revolution. A simultaneously occurring movement towards 

an analytic, technology-based approach to fighting 

crime gave birth to modern forensics. 

Physical fingerprinting made its way to the US by 1904, 

but it was not until 80 years later that a case was solved with 

DNA fingerprinting. In March of 1985, DNA evidence of 

a young boy’s parentage saved him from deportation, capturing 

the romantic sentiments of the public and increasing 

interest in DNA fingerprinting. The first application in 

a forensic case occurred in 1987, when a man was implicated 

in a rape crime. As more cases flooded in, the 1990’s 

became a golden research age of DNA fingerprinting, followed 

by two decades of engineering and implementation. 

In the last 10 years alone, fingerprinting methods have improved 

substantially with the advent of portable crime labs 

and the increased use of chemical analysis. Jeffreys’ original 

technology is now obsolete, as techniques have become 

more sensitive and straightforward. 

In classical DNA fingerprinting, isolated DNA is cut 

at known points along the strand. These fragments are 

then separated by size with a process called agarose electrophoresis, 

which capitalizes on the negative charge of 

DNA by attracting it towards a positive charge. As DNA 

fragments migrate on a gel, shorter segments travel faster 

than longer ones. This movement of DNA is later visualized 

using radioactive probes that stick to the fragments. 

The sizes of these DNA fragments differ between 

people because everyone has variation in their DNA sequences. 

There were many drawbacks to the early methods of 

DNA fingerprinting, including DNA quality issues, statistical 

errors, and a difficulty obtaining optimal samples 

from crime scenes. To address these limitations, newer 

techniques have been developed. Starting in the early 

1990s, DNA fingerprinting methods gradually became 

based on polymerase chain reactions (PCR), a technology 

that selectively amplifies a small sample of DNA to 

generate thousands to millions of copies of a particular 

sequence. Using PCR has improved sensitivity, speed, 

and genotyping precision. Analysts also began to study 

short tandem repeats, repetitive sequences of DNA, because 

of their variation among individuals. It is now possible 

to generate an individual’s unique genetic code, 

eliminating the chance of a false positive because it is 

highly improbably that two individuals will have identical 

markers at each location examined within their 

DNA. In fact, the odds exceed one in a billion. 

So where, one might ask, does the future of forensics 

lie? With the emergence of next generation sequencing 

technologies, many believe that DNA sequencing, 

which actually identifies each base pair (A, T, C, G) in 

the genome, will replace current methods based on fragment 

length analysis. The cost of sequencing has fallen 

dramatically, and if accuracy and reliability continue to 

increase, the process will become fast, automated, and 

perhaps even possible on-site. So if you commit a crime 

anytime soon—you will likely be caught. 


March 2016 


35

UNDERGRADUATE PROFILE 

OLIVIA PAVCO-GIACCIA (JE ‘16) 

FROM THE LAB TO LABCANDY 

►BY STEPHANIE SMELYANSKY 

Meet Olivia Pavco-Giaccia. She is a typical Yale College student 

majoring in cognitive science. She plays the cello in Low Strung—an 

all-cello rock group—played with the Yale Symphony Orchestra, and 

she is in the Kappa Alpha Theta sorority. She is also the CEO of her 

own social enterprise company. 

Olivia Pavco-Giaccia is the founder and CEO of LabCandy, a company 

aimed at getting girls and boys in kindergarten through third grade 

interested in the sciences. LabCandy sells kits that each contain a colorful 

lab coat, a DIY goggle kit, and an interactive storybook featuring 

a young girl who uses science to save the day. The kit is designed to 

promote the message that scientists are not only old men in a white lab 

coats. Young scientists with the kit can personalize their own lab style, 

identify with the main character in a science book, and even complete 

some of the experiments from the book. Essentially, the kit offers an accessible 

connection to science from a young age. 

Pavco-Giaccia herself would not have become interested in science 

if not for a stroke of luck. “I had never thought of myself as a ‘science 

kid, ’ but got really lucky, and had the incredible experience of studying 

with a few amazing science teachers,” Pavco-Giaccia said. Her teachers—namely 

her seventh grade biology teacher and her high school advisor—cinched 

her interest in science. But her interest in neurobiology 

stemmed from her family. According to Pavco-Giaccia, her grandfather’s 

struggle with Alzheimer’s disease and her own experience with 

a serious concussion inspired her to enroll in a summer neurobiology 

course during high school, sparking her subsequent interest in cognitive 

science. Even as a senior in the midst of her thesis, Pavco-Giaccia 

has only kind words for her major. “It’s a relatively small major filled 

with really cool people. The interdisciplinary opportunities for study 

IMAGE COURTESY OF OLIVIA PAVCO-GIACCIA 

►Pavco-Giaccia watches over a team of young scientists as they 

show her the goggles they decorated. 

are exciting, and the professors are just fabulous,” Pavco-Giaccia said. 

The inspiration for LabCandy came long before Pavco-Giaccia’s college 

years began, however. The summer after her junior year, Pavco-Giaccia 

worked in a neurobiology lab at Stanford. While conducting research, 

she maintained a science blog targeted at young girls. One day, 

she posted a picture of her bedazzled lab goggles and was amazed by 

the response she received. “I was flooded with comments from little 

girls asking me where I got the goggles,” Pavco-Giaccia said. That moment 

resonated with Pavco-Giaccia, but amidst a tide of college applications 

and the obligations of senior year, her idea to promote the goggles 

was put onto the backburner. 

It was not until her first year at Yale that Pavco-Giaccia reconsidered 

the goggles. She saw a flyer posted by the Yale Entrepreneurial Institute 

(YEI) and made an appointment with the staff to chat about her idea to 

make sparkly goggles for young girls. She applied for, and was subsequently 

awarded, a YEI fellowship to stay in New Haven over the summer 

in order to build LabCandy. She was the youngest summer fellow 

ever. She spent that summer talking to parents, educators, and scientists, 

trying to refine her product. After these discussions, Pavco-Giaccia 

realized that she needed to move beyond goggles to create a better 

product, so she added a lab coat and interactive storybook to the kit. 

When she pitched the complete kit at the YEI summer pitch competition, 

she tied for first place and was awarded prize money to start selling 

prototype kits. 

Mass-production turned out to be the biggest challenge. To fund the 

project, Pavco-Giaccia turned to Kickstarter. The campaign aimed to 

raise $20,000 in 30 days, but it reached its goal after just three days, and 

raised more than $30,000. Afterwards, Pavco-Giaccia collaborated with 

the Yale Publishing and Printing Services to produce the storybooks. 

Finding a company to produce the lab coats was more challenging. She 

had a difficult time finding the exact type of fabric she needed: a thick, 

brightly-colored cotton fabric. After multiple trips to New York City’s 

garment district led her to a manufacturer Minnesota able to produce 

the lab coats according to her specifications. Although the distance between 

Yale and Minnesota made communication difficult, the partnership 

was successful and the lab coats were made. Finally, Pavco-Giaccia 

had a complete, sellable kit. 

In just a few months, Olivia Pavco-Giaccia will graduate from Yale 

already owning and running a successful company. She has created a 

product that addresses gender in science. After graduation, Pavco-Giaccia 

has several options, but she knows she will continue with Lab- 

Candy. In the meantime, her goal is to fully enjoy her last semester at 

Yale. 


ALUMNI PROFILE 

FRANCIS COLLINS (GRD ‘74) 

GUIDING THE RESEARCH REVOLUTION 

►BY KEVIN BIJU 

As Director of the National Institutes of Health (NIH), Francis Collins 

combines the personal fortitude of a leader with the analytical 

understanding of a researcher to oversee the largest medical research 

institute in the world. Prior to this, Collins successfully directed the 

Human Genome Project, which was widely considered to be the 

greatest bioscience research endeavor in history. He is a man of many 

talents, acquired through an interesting journey to the top. 

Born in 1950, Collins developed a childhood fascination with chemistry 

and mathematics. At the young age of 16, he enrolled in the University 

of Virginia believing he was destined to become a chemistry 

professor. He swiftly completed every chemistry and physics course 

available to him. “I completely ignored biology because it seemed a bit 

messy to me, and frankly, it is a little bit messy,” Collins said. 

After obtaining his B.S. in chemistry, Collins came to Yale to earn a 

Ph.D. in physical chemistry. Around that time, he enrolled in a molecular 

biology course that completely changed his attitude towards the 

life sciences. “So I had a bit of a crisis at that point…I had my whole 

life planned to become an academic chemist and now this whole field 

was beckoning to me,” Collins said. 

Collins reasoned that he could prepare for research in the life sciences 

by attending medical school. He received eight years of medical 

training at UNC Chapel Hill, before he found himself back at Yale 

researching molecular biology. After learning how to conduct experiments 

at the DNA level, Collins was prepared for his next job: 

gene-hunting. 

From 1984 to 1993, Collins worked at the University of Michigan 

to discover the genes responsible for several inherited diseases. There, 

he worked with a group of scientists who had an ambitious plan to 

map the genetic underpinnings of cystic fibrosis, a disease characterized 

by respiratory infection due to abnormally thick mucus. It was a 

monumental challenge that would truly test Collins’ skills in human 

genetics. “There was nothing to guide us; we were feeling our way in 

the dark here,” Collins said. 

After five years of intensive hunting, Collins’ team finally discovered 

the elusive genes. This was a huge moment for the entire field. 

Collins’ team demonstrated the feasibility of gene hunting, and the 

versatile methodology behind it—called positional cloning—became 

an important tool for molecular biologists. Perhaps most importantly, 

Collins’ success convinced the scientific community of the viability of 

the Human Genome Project, the NIH’s 15 year plan to map all genes 

specific to the human race. 

Collins, excited to participate in this once-in-a-lifetime project, applied 

for a grant from the Human Genome Project. But the NIH had 

IMAGE COURTESY OF NIH 

►From left, HHS Secretary Kathleen Sebelius, NIH Director Dr. 

Francis Collins and President Barack Obama tour the Mark Hatfield 

Clinical Research Center at NIH. 

other plans for him. “They asked me to lead the Human Genome Project, 

something I had never considered before,” Collins said. At first, he 

was hesitant to become a public employee. Nevertheless, Collins accepted 

this monumental challenge, recognizing that there would only 

be one Human Genome Project in history. 

Collins faced pressures from many fronts. Much of the scientific 

community thought the project was going to be too expensive. In addition, 

the manual DNA sequencing system had to be converted to an 

automated one. Once the technology was finally developed, Collins 

formed international teams of scientists. Throughout the entire process, 

Collins served as Project Manager, a leader who coordinated the 

different teams and solved outstanding problems. “We developed a 

wonderful sense of camaraderie around this goal, because we appreciated 

its importance to medicine,” Collins said. Despite the challenges, 

they managed to sequence the human genome by 2003, two years 

earlier than planned. 

Soon after this accomplishment, Collins received a call from President 

Obama, and he was promptly sworn in as the Director of the 

NIH. Initially a student who ignored the “messy” field of biology, Collins 

now oversees one of the most important institutions in the biology 

research realm. He says it has definitely broadened his horizons. 

Collins is excited to see where medicine will go next in the fields 

of neuroscience, infectious disease, and immunotherapy. “It has been 

quite a ride. And there is still a huge frontier out there just waiting for 

us to explore.” 


March 2016 


37

FEATURE 

documentary review 

SCIENCE IN THE SPOTLIGHT 

DOCUMENTARY REVIEW : RESISTANCE 

►BY ZACHARY MILLER 

If you have ever taken antibiotics, you have also taken part in 

perhaps the largest unplanned experiment in medical history. It 

began nearly a hundred years ago, with their discovery. In the past 

half century, humans have used them profligately—popping antibiotic 

pills at the hint of illness, feeding them to farm animals, 

and flushing them into the environment with abandon. This experiment 

of sorts has proceeded without design or careful records, 

and with little sense of what consequences might result. 

In recent decades, however, one outcome has become terrifyingly 

clear: our incessant use of antibiotics has bred bacteria 

immune to them altogether. As bacteria are exposed to antibiotics, 

most are wiped out, but a few lucky cells hold genes that 

confer resistance. When exposed to antibiotics, these fluky microbes 

have a tremendous advantage compared to their susceptible 

bacterial peers. Their descendants quickly come to dominate 

the population, and soon the entire strain becomes resistant. 

This process and its unsettling consequences are the subject of Resistance, 

a new documentary directed by Michael Graziano. The film 

recounts humanity’s love affair with antibiotics, medicines which 

have enabled the near total defeat of bacterial disease—at least in developed 

nations. But our reckless use of these “miracle drugs” threatens 

to return us to the days when every infection could be deadly. 

Antibiotics have been overprescribed and taken for granted, the film 

argues. Every unnecessary use—for instance, antibiotics taken to 

treat a viral cold, which remains unaffected—speeds bacteria toward 

resistance. As resistance becomes widespread, once potent drugs become 

ineffective, and we march toward a world without antibiotics. 

Resistance is surprisingly engaging, without descending into fear 

mongering. The film takes pains to convey the severity and urgency 

of the problem, but its treatment is level-headed. Graziano clearly recognizes 

the subtleties that have made antibiotic resistance a thorny issue, 

and the film’s scientific explanations are laudably cogent and clear. 

Graziano also deserves great credit for tackling an issue which 

can seem distant and dull. The film is littered with strikingly 

beautiful microscopy, which provides a watchable counterweight 

to hospital room shots and interviews with academics. Resistance 

also makes good use of archival footage to situate the problem 

of antibiotic resistance historically. Flitting between these 

clips and images of futuristic laboratories conveys a sense that 

gains against bacterial infection are precarious. A world of resistance 

and medical backslide is an ever-present possibility. 

Interviews with scientists and policy-makers drive the film, 

but it is the interviews with everyday people ravaged by drug-resistant 

infections that convey its relevance. The message of these 

heart-wrenching stories is unmistakable: Bacteria will only become 

more resistant, and, unless we change our ways, no one is safe. 

While Resistance offers glimpses at new, sustainable approaches to 

antibiotics, the focus of the film is on problems, not solutions. And it 

leaves the viewer with little doubt that we are facing a serious problem. 

This alone is remarkable. Resistance marshals stark facts and 

pairs them with lucid, accessible scientific explanations, leaving even 

skeptics convinced. It should be a model for scientific filmmaking. 

DOCUMENTARY REVIEW : RACING EXTINCTION 

►BY MIGUEL LEPE 

Racing Extinction, a Discovery Channel documentary released in 

2015, is full of beautiful and horrifying images that are not easily forgotten. 

From majestic whale sharks to slaughtered manta rays, the subjects 

of this new documentary reveal nature’s beauty and force viewers 

to confront the detrimental effects of human activity on the planet. 

The documentary introduces its viewers to the Anthropocene, 

the geological age that began when human activities became 

a driving force for major geological changes. The film 

mixes cogent scientific facts with captivating images to convey 

the urgency of the crisis facing our planet—an emergency stemming 

from global climate change and mass species extinction. 

Scientists predict that within the next 100 years, 50 percent 

of Earth’s species will become extinct if we continue 

down this path. Species go extinct regardless of human interference, 

but in the next decade alone, humans will drive 

other species to extinction ten times faster than normal. 

Most of the film is dedicated to ocean quality because oceans are 

crucial to global stability. “When carbon dioxide is emitted into the 

atmosphere, between a third and a half gets absorbed by the oceans, 

making them more acidic,” said Louie Psihoyos, director of Racing 

Extinction, in the documentary. This increased acidity kills phytoplankton—the 

organisms responsible for producing half of the 

world’s oxygen supply—and harms many other oceanic creatures. 

The film also highlights the illegal market for shark 

fins in China, which claims the lives of 1.3 to 2.7 million 

sharks every year. Sharks have survived four mass extinctions 

in the earth’s history, but now human activity has decreased 

the shark population by 90 percent in one generation. 

The documentary exposes specific ways that humans contribute 

to the changing geochemistry of the planet. According 

to Psihoyos, our livestock contribute more greenhouse gases 

to the atmosphere than all direct emissions from the transportation 

sector. However, the film also recognizes our ability to 

solve these problems by providing pathways for people to live 

more sustainably: “If every American skipped meat and cheese 

just one day a week for a year, it would be like taking 7.6 million 

cars off the road,” Psihoyos narrated in Racing Extinction. 

The film concedes that large-scale geological changes are not 

simple problems to solve, but it advocates for people to find a 

way to help alleviate the problem. Overall, Racing Extinction 

drives home the message that saving the planet is worthwhile 

by unveiling the hidden beauty of the earth. The film inspires 

its viewers to maintain hope and convinces them to see and 

hear the beauty and vibrancy of the world that surrounds them. 


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