YSM Issue 88.4

Yale Scientific
Established in 1894
THE NATION’S OLDEST COLLEGE SCIENCE PUBLICATION
NOVEMBER 2015 VOL. 88 NO. 4
Ancient Ink
MODERN SCRIPTS
Computers master medieval texts

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NEWS
Letter From the Editor
Banned Drug Repurposed for Diabetes
ArcLight Illuminates Neurons
New Organ Preservation Unit
Surprising Soft Spot in the Lithosphere
An Unexpected Defense Against Cancer
New Device for the Visually Impaired
Energy Lessons from Hunter-Gatherers
Mosquitoes Resistant to Malaria
FEATURES
Environment
Climate Change Spikes Volcanic Activity
Cell Biology
How Radioactive Elements Enter a Cell
Yale Scientific
Established 1894
CONTENTS
NOVEMBER 2015 VOL. 88 ISSUE NO. 4
24
Ancient Ink,
Modern Scripts
Through months of a
squirrel’s cold slumber,
neurons generate
their own heat to keep
functioning. Our cover
story explains this
feat of the nervous
system and explores
what it might mean for
humans.
ART BY CHRISTINA ZHANG
Black Hole with a
13
Growth Problem
22
ON THE COVER
Ancient Ink,
Modern Scripts
A new algorithm allows computer
scientists to unlock the secrets of
medieval manuscripts. From pen to
pixel, researchers are using science
to better understand historical texts.
A supermassive black hole challenges the foundations
of astrophysics, forcing astronomers to update the
rule book of galaxy formation.
28
Robotics
Robots with Electronic Skin
30
31
32
34
35
Computer Science
Predicting Psychosis
Debunking Science
San Andreas
Technology
The Future of Electronics
Engineering
Who Lives on a Dry Surface Under the Sea?
Science or Science Fiction?
Telepathy and Mind Control
16
Tiny Proteins with
Big Functions
Contrary to common scientific belief,
proteins need not be large to have
powerful biological functions.
18
IMAGE COURTESY OF MEG URRY
East Meets West in
Cancer Treatment
A Yale professor brings an ancient remedy
to the forefront, showing that traditional
herbs can combat cancer.
36
Grey Meyer MC ‘16
37
Michele Swanson YC ‘82
38
Q&As
Do You Eat with Your Ears?
How Do Organisms Glow in the Dark?
20
Nature’s
Blueprint
ART BY CHANTHIA MA
Scientists learn lessons from nature’s greenery, modeling
the next generation of solar technology on plant cells.
November 2015
3

FEATURE
book reviews
SPOTLIGHT
SCIENCE IN THE SPOTLIGHT
HOW TO CLONE A MAMMOTH Captivates Scientists and Non-scientists Alike
BY ALEC RODRIGUEZ
Science fiction novels, TV shows, and movies have time and time
again toyed with the cloning of ancient animals. But just how close
are we to bringing these species, and our childhood fantasies, back
to life?
While animals were first cloned about 20 years ago, modern
technology has only recently made repopulating some areas of the
world with extinct species seem feasible. In her book, How to Clone a
Mammoth, evolutionary biologist Beth Shapiro attempts to separate
facts from fiction on the future of these creatures. Her research
includes work with ancient DNA, which holds the key to recreating
lost species. The book, a sort of how-to guide to cloning these
animals, takes us step-by-step through the process of de-extinction.
It is written to engage scientific and non-scientific audiences alike,
complete with fascinating stories and clear explanations.
To Shapiro, de-extinction is not only marked by birth of a cloned
or genetically modified animal, but also by the animal’s successful
integration into a suitable habitat. She envisions that researchers
could clone an extinct animal by inserting its genes into the genome
of a related species. Along these lines, Shapiro provides thoughtprovoking
insights and anecdotes related to the process of genetically
engineering mammoth characteristics into Asian elephants. She
argues that the genetic engineering and reintroduction of hybrid
animals into suitable habitats constitutes effective “clonings” of
extinct species.
BY AMY HO
Mark Steyn’s recent A Disgrace to the Profession attacks Michael E.
Mann’s hockey stick graph of global warming — a reconstruction of
Earth’s temperatures over the past millennium that depicts a sharp
uptick over the past 150 years. It is less of a book than it is a collection of
quotes from respected and accredited researchers, all disparaging Mann
as a scientist and, often, as a person.
Steyn’s main argument is that
Mann did a great disservice to science
when he used flawed data to create a
graph that “proved” his argument
about Earth’s rising temperatures.
Steyn does not deny climate change,
nor does he deny its anthropogenic
causes. His issue, as he puts it, is
with the shaft of the hockey stick,
not the blade. His outrage lies not
only in the use of poor data, but in
Mann’s deletion of data in ignoring
major historical climate shifts such
as the Little Ice Age and the Medieval
Warm Period.
IMAGE COURTESY OF AMAZON
While some sections of the book
are a bit heavy on anecdotes, most
are engaging, amusing, and relevant
enough to the overall chapter themes
to keep the book going. Shapiro
includes personal tales ranging from
asking her students which species
they would de-extinct to her struggle
trying to extract DNA from ember.
The discussion of each core topic feels
sufficient, with a wealth of examples.
Shapiro tosses in some comments
on current ecological issues here
and there, and for good measure, she busts myths like the idea
that species can be cloned from DNA “preserved” in ember. Sorry,
Jurassic Park.
The book is a quick, easy read — only about 200 pages — that would
be of interest to any biology-inclined individual and accessible even
to the biology neophyte. Shapiro summarizes technological processes
simply and with graphics for visual learners. Most of all, Shapiro’s
book leaves the reader optimistic for the future of Pleistocene Park
— a habitat suitable for the reintroduction of mammoths.
Our childhood fantasies, when backed with genetic engineering,
could be just around the corner.
A DISGRACE TO THE PROFESSION Attacks the Man Instead of the Science
To Steyn, the Intergovernmental Panel on Climate Change (IPCC)
and all those who supported the hockey stick graph also did a disservice
to science by politicizing climate change to the extent that it gives
validity to deniers. However, Steyn may be giving these doubters yet
more ammo, because he has done nothing to de-politicize the issue.
Steyn claims that Mann has drawn his battle lines wrong — but then,
so has Steyn, by attacking Mann instead of focusing on the false science.
Steyn’s writing style is broadly appealing, but his humor underestimates
his audience. His colloquial tone could be seen as a satirical take on
what Steyn refers to as Mann’s “cartoon climatology,” but it eventually
subverts his argument by driving the same points over and over while
never fully delving into scientific details. Although Steyn champions a
nuanced view of climate science, his own nuance only goes so far as to
tell his readers that they should be less certain, because meteorology and
climate science are uncertain.
“The only constant about climate is change,” Steyn points out,
advocating for us to better understand climate and to adapt to changes as
they come. It is an important point that deserves more attention than it
gets in the book. A Disgrace to the Profession is an entertaining read that
sounds like a blogger’s rant. Steyn makes few points that are especially
compelling, but then insists on hammering them in.
IMAGE COURTESY OF PRINCETON UNIV. PRESS
4 November 2015

F R O M T H E E D I T O R
Here at the Yale Scientific Magazine, we write about science because it
inspires us. Some of the biggest responsibilities in science fall to our smallest
molecules. Miniscule proteins called ubiquitin ligases are tasked with identifying
and attacking deviant cancer cells (pg. 11). Such power can be dangerous. The
simplest proteins known to exist are capable of spinning cell growth out of
control to cause tumors (pg. 16) — dangerous, yes, but still impressive.
And the researchers we interview are inspiring, in their creative approaches
to answering questions and in their dedication to making a real-world impact.
Want to know how human metabolism has changed with the modernization of
society? Find people who continue to live as hunter-gatherers for comparison
(pg. 10). Intrigued by the level of detail in medieval manuscripts? In our cover
story, scientists take on the vast medieval corpus with an innovative and efficient
computer algorithm (pg. 22). Others are extending the reach of their research
far beyond laboratory walls. A project for a Yale engineering class turned into a
new device that better preserves human organs for transplant, which became the
company Revai (pg. 7). A collaboration between a mechanical engineer in New
Haven and a theater company in London has culminated in exciting technology
that allows the visually impaired to experience their surroundings (pg. 9).
For this issue of our publication, we asked also: What inspires these scientists?
Their research questions can stem from a single curiosity in the realm of biology
or chemistry or physics. Often, they’re motivated to improve some aspect of the
world, whether it’s human health or the environment. Scientists design solutions
to achieve these improvements. For ideas, they turn to history: An ancient
Chinese herbal remedy has resurfaced as a powerful 21st century drug (pg. 18).
Or, they look to nature: Solar panels might be more effective if they were modeled
after plant cells — after all, the basic operation of both solar cells and plant cells
is to convert sunlight into useable energy (pg. 20). Even everyday electronics can
be inspired by nature — particularly, by the inherent ability of certain materials
to self-assemble (pg. 32).
Between these covers, we’ve written about a diversity of topics in science,
bringing you stories from the lab, from the field, and from the far corners of
the universe. Whether you’re fascinated by the cosmos, natural disasters, or
advanced robots, we hope you’ll see inspiration in this issue of the Yale Scientific.
Yale Scientific
Established in 1894
THE NATION’S OLDEST COLLEGE SCIENCE PUBLICATION
NOVEMBER 2015 VOL. 88 NO. 4
Ancient Ink
MODERN SCRIPTS
A B O U T T H E A R T
Computers master medieval texts
Payal Marathe
Editor-in-Chief
The cover of this issue, designed by arts editor
Christina Zhang, features the algorithm that
identifies the number of colors on digitized
medieval manuscripts. The art depicts the
process of categorizing pixels using a binary code.
Developed by Yale computer science and graphics
professor Holly Rushmeier, this technology could
help researchers decrypt medieval texts.
Editor-in-Chief
Managing Editors
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NEWS
in brief
Banned Drug Repurposed for Diabetes
By Cheryl Mai
PHOTO BY CHERYL MAI
Rachel Perry, lead author of this
study, is a postdoctoral fellow in the
Shulman lab.
The molecule behind a weight-loss pill
banned in 1938 is making a comeback.
Professor Gerald Shulman and his research
team have made strides to reintroduce 2,4
dinitrophenol (DNP), once a toxic weight-loss
molecule, as a potential new treatment for type
2 diabetes.
Patients with type 2 diabetes are insulin
resistant, which means they continue to
produce insulin naturally, but their cells
cannot respond to it. Previous research by the
Shulman group revealed that fat accumulation
in liver cells can induce insulin resistance, nonalcoholic
fatty liver disease, and ultimately
diabetes. Shulman’s team identified DNP, which
reduces liver fat content, as a possible fix.
DNP was banned because it was causing
deadly spikes in body temperature due to
mitochondrial uncoupling. This means the
energy in glucose, usually harnessed to produce
ATP, is released as heat instead. Shulman’s
recent study offers a new solution to this old
problem: CRMP, a controlled release system
which limits the backlash of DNP on the body.
CRMP is an orally administered bead of
DNP coated with polymers that promote the
slow-release of DNP. When the pace of DNP
release is well regulated, overheating is much
less likely to occur. Thus, patients could benefit
from the active ingredients in the drug without
suffering potentially fatal side effects.
So far, findings have been promising: no
toxic effects have been observed in rats with
doses up to 100 times greater than the lethal
dose of DNP.
“When giving CRMP, you can’t even pick up
a change in temperature,” Shulman said.
Results also include a decrease in liver fat
content by 65 percent in rats and a reversal of
insulin resistance. These factors could be the
key to treating diabetes.
“Given that a third of Americans are projected
to be diabetic by 2050, we are greatly in need of
agents such as this to reverse diabetes and its
downstream sequelae,” said Rachel Perry, lead
author of the study.
ArcLight Illuminates Neuronal Networks
By Archie Rajagopalan
IMAGE COURTESY OF PIXABAY
With ArcLight, real-time imaging
of neuronal networks could lead to a
major breakthrough in understanding
the brain’s many components.
Scientists have engineered a protein that will
more accurately monitor neuron firing. The
protein, called ArcLight, serves as a fluorescent
tag for genes and measures voltage changes in
real time, offering new insight on how nerve
cells operate and communicate.
Neuron firing involves the rapid influx of
calcium ions from outside of the neuron’s
membrane. Proteins that illuminate in the
presence of increased calcium levels can
therefore track the completion of an action
potential. For this reason, calcium sensors are
commonly used as a proxy for action potential
measurements. However, because calcium
changes occur more slowly than voltage
changes, calcium sensors do not provide
precise measurements of neuron signaling.
In a recent study by Yale postdoctoral fellow
Douglas Storace, ArcLight was shown to be
a more efficient candidate for this job. In the
experiment, either ArcLight or a traditional
calcium-based probe was injected into the
olfactory bulb of a mouse. Simultaneously,
using an epifluorescence microscope, Storace
observed changes in fluorescence triggered
by the mouse sniffing an odorant. Because
ArcLight reports rapid changes in the electrical
activity of neurons, Storace and his colleagues
were able to obtain more direct measurements
of neuron firing with ArcLight compared to
ordinary calcium sensors.
In addition to monitoring voltage changes
directly, ArcLight is genetically encoded and
can be targeted to specific populations of cells.
This allows scientists to monitor the electrical
activity of different cell types and may provide
more information on how different neuronal
pathways interact.
“A more accurate way of monitoring
the voltage in neurons gives us a lot more
information about their activity,” Storace said.
“Potentially, this discovery will give us enough
information about neurons to lead to a major
breakthrough.”
6 November 2015

in brief
NEWS
New Startup Develops Organ Preservation Unit
By Newlyn Joseph
An organ transplant comes with a slew of
complications. Perhaps the most commonly
overlooked problem is the preservation of
donor tissue prior to translpant. Current means
of storing intestines before they are transplanted
involve a simple container filled with ice. Until
now, there has been little progress in developing
more effective, efficient preservation strategies.
The nascent company Revai, the result of
a collaboration between the Yale Schools of
Engineering, Medicine, and Management,
addresses the challenge of preserving intestines
for transplant. Company leaders John Geibel,
Joseph Zinter, and Jesse Rich have developed
the Intestinal Preservation Unit, a device
that perfuses the intestine’s lumen and blood
supply simultaneously and independently, at a
rate determined by the surgeon. This “smart”
device collects real-time data on temperature,
perfusion time, and pump flow rates, allowing
doctors to monitor all vital storage parameters.
The technology has the potential to extend
the lifetime of intestines in between the organ
donor and the transplant recipient.
“It’s the first time we have something new for
this particular organ,” Geibel said.
Revai has demonstrated that the preservation
unit decreases the rate of necrosis, or massive
cell death, in pig intestinal tissue. This exciting
result held up when the unit was tested on
human samples through partnerships with
New England organ banks.
“We’re the only team currently presenting
peer-reviewed data on testing with human
tissue,” said CEO Jesse Rich, proud that Revai is
a frontrunner in this area of exploration.
Students in a Yale class called Medical Device
Design and Innovation built the first functional
prototype of the Intestinal Preservation Unit
for testing. The device went on to win the
2014 BMEStart competition sponsored by the
National Collegiate Inventors and Innovators
Alliance. Revai plans to continue product
development and testing for the unit, and
will seek FDA approval to commercialize the
device.
PHOTO BY HOLLY ZHOU
Joseph Zinter and Jesse Rich look at
a model of their Intestinal Preservation
Unit.
Geologists Find Surprising Softness in Lithosphere
By Danya Levy
As a student 40 years ago, Shun-ichiro
Karato learned of the physical principles
governing grain boundaries in rocks, or
the defects that occur within mineral structures.
Now, as a Yale professor, he has applied
these same concepts to a baffling geophysical
puzzle. Karato has developed a new
model to explain an unexpected decrease in
the stiffness of the lithosphere.
Earth’s outer layers of rock include the
hard lithosphere — which scientists previously
assumed to be stiff — and the softer
asthenosphere. Seismological measurements
performed across North America
over the past several years have yielded a
surprising result.
“You should expect that the velocities [of
seismological waves] would be high in the
lithosphere and low in the asthenosphere,”
Karato said. Instead, a drop was observed
in the middle of the lithosphere, indicating
softness. With the help of colleagues Tolulope
Olugboji and Jeffrey Park, Karato came
up with a new explanation for these findings.
Recalling from his studies that grain
boundaries can slide to cause elastic deformation,
Karato made observations at a
microscopic level and showed that mineral
weakening occurs at lower temperatures
than previously thought.
Even if mineral grains themselves are
strong, the grain boundaries can weaken
at temperatures slightly below their melting
point. As a result, seismic wave observations
show increased softness even while
the rock retains large-scale strength.
Karato noted that there is still work to be
done in this area. But his research is a significant
step forward in understanding the
earth’s complex layers.
“This is what I love,” he said. “Looking at
the beauty of the earth and then introducing
some physics [sometimes] solves enigmatic
problems.”
PHOTO BY DANYA LEVY
Professor Karato, who works in
the Kline Geology Laboratory building,
makes use of some of the most advanced
high-pressure equipment.
November 2015
7

NEWS
medicine
AN UNEXPECTED DEFENSE
Lupus-causing agent shows potential for cancer therapy
BY ANSON WANG
Some of the world’s deadliest diseases occur when the body
begins to betray itself. In cancer, mutated cells proliferate
and overrun normal ones. Lupus, an autoimmune disease,
occurs when the body’s immune system begins to attack its
own cells. But what if the mechanisms of one disease could
be used to counteract another?
This thought inspired recent work by James Hansen, a Yale
professor of therapeutic radiology. Hansen transformed
lupus autoantibodies — immune system proteins that target
the body’s own proteins to cause lupus — into selective
vehicles for drug delivery and cancer therapy.
His focus was 3E10, an autoantibody associated with
lupus. Hansen and his team knew 3E10 could penetrate
a cell’s nucleus, inhibiting DNA repair and sparking
symptoms of disease. What remained a mystery was the
exact mechanism by which 3E10 accomplishes nuclear
penetration, and why the autoantibody is apparently
selective for tumor cells. Unlocking these scientific secrets
opened up new possibilities to counteract disease, namely,
by protecting against cancer.
What Hansen’s team found was that 3E10’s ability to
penetrate efficiently into a cell nucleus is dependent on
the presence of DNA outside cell walls. When solutions
absent of DNA were added to cells incubated with 3E10,
no nuclear penetration occurred. With the addition of
purified DNA to the cell solution, nuclear penetration by
3E10 was induced immediately. In fact, the addition of
solutions that included DNA increased nuclear penetration
by 100 percent. The researchers went on to show that the
actions of 3E10 also rely on ENT2, a nucleoside transporter.
Once bound to DNA outside of a cell, the autoantibody can
be transported into the nucleus of any cell via the ENT2
nucleoside transporter.
“Now that we understand how [3E10] penetrates into
the nucleus of live cells in a DNA dependent manner, we
believe we have an explanation for the specific targeting of
the antibody to damaged or malignant tissues where DNA
is released by dying cells,” Hansen said.
Because there is a greater presence of extracellular DNA
released by dying cells in the vicinity of a tumor, antibody
penetration occurs at a higher rate in cancerous tissue. This
insight holds tremendous meaning for cancer therapies.
If a lupus autoantibody were coupled with an anti-cancer
drug, scientists would have a way of targeting that drug to
tissue in need. In this way, what causes one disease could be
harnessed to treat another.
The primary biological challenge for cancer therapy
is to selectively target cancer cells while leaving healthy
ones alone. The 3E10 autoantibody is a promising solution
because it offers this specificity, a direct path to the tumor
cells that will bypass all cells functioning normally. The
molecule could carry therapeutic cargo, delivering anticancer
drugs to unhealthy cells in live tissue.
The Yale researchers were pleased with their next step as
well — they showed that these engineered molecules were
in fact tumor-specific. Tissue taken from mice injected with
flourescently tagged autoantibodies showed the presence
of the antibody in tumor cells, but not normal ones after
staining.
Now, Hansen and his colleagues are looking into using
the 3E10 and their engineered molecules to kill cancer
cells. Since some cancer cells are already sensitive to DNA
damage, inhibition of DNA-repair by 3E10 alone may
be enough to kill the cell. Normal cells with intact DNA
repair mechanisms would be likely to resist these effects,
making 3E10 nontoxic to normal tissue. The researchers are
working to optimize the binding affinity of 3E10 so that it
can penetrate cells more efficiently and can exert a greater
influence on DNA repair. The goal is to conduct a clinical
trial within the next few years.
In the search for more effective drugs against cancer,
answers can emerge from the most extraordinary places.
“Our discovery that a lupus autoantibody can potentially be
used as a weapon against cancer was completely unexpected.
3E10 and other lupus antibodies continue to surprise and
impress us, and we are very optimistic about the future of
this technology,” Hansen said.
The recent study was published in the journal Scientific
Reports.
IMAGE COURTESY OF JAMES HANSEN
James Hansen (left) pictured with postdoctoral research
associate Philip Noble.
8 November 2015

technology
NEWS
NEW DEVICE FOR THE VISUALLY IMPAIRED
Collaboration yields innovative navigation technology
BY AARON TANNENBAUM
Despite its small size and simple appearance, the Animotus
is simultaneously a feat of engineering, a work of art, and a
potentially transformative community service project.
Adam Spiers, a postdoctoral researcher in Yale University’s
department of mechanical engineering, has developed a
groundbreaking navigational device for both visually impaired
and sighted pedestrians. Dubbed Animotus, the device can
wirelessly locate indoor targets and changes shape to point
its user in the right direction towards these targets. Unlike
devices that have been created for visually impaired navigation
in the past, Spiers’ device communicates with its users by way
of gradual rotations and extensions in the shape of its body.
This subtly allows the user to remain focused on his or her
surroundings. Prior iterations of this technology communicated
largely through vibrations and sound.
Spiers created Animotus in collaboration with Extant, a
visually impaired British theater production company that
specializes in inclusive performances. The device has already
been successful in Extant’s interactive production of the novel
“Flatland,” and with further research and development the
Animotus may be able to transcend the realm of theater and
dramatically change the way in which the visually impaired
experience the world.
Haptic technology, systems that make use of our sense of
touch, is most widely recognized in the vibrations of cell phones.
The potential applications of haptics, however, are far more
complex and important than mere notifications. Spiers was
drawn to the field of haptics for the implications on medical and
assistive technology. In 2010, he first collaborated with Extant to
IMAGE COURTESY OF ADAM SPIERS
Animotus has a triangle imprinted on the top of the device to
ensure that the user is holding it in the proper direction.
apply his research in haptics to theater production.
To facilitate a production of “The Question,” an immersive
theater experience set in total darkness, Spiers created a
device called the Haptic Lotus, which grew and shrunk in the
user’s hands to notify him when he was nearing an intended
destination. The device worked well, but could only alert
users when they were nearing their targets, instead of actively
directing them to specific sites. As such, the complexity of the
show was limited.
Thanks to Spiers’ newly designed Animotus, Extant’s 2015
production of “Flatland” was far more complex. Spiers and
the production team at Extant sent four audience members at
a time into the pitch-black interactive set, which was built in
an old church in London. Each of the four theatergoers was
equipped with an Animotus device to guide her through the set
and a pair of bone-conduction headphones to narrate the plot.
The Animotus successfully guided each audience member on a
unique route through the production with remarkable accuracy.
Even more impressive, Spiers reported that the average
walking speed was 1.125 meters per second, which is only 0.275
meters per second slower than typical human walking speed.
Furthermore, walking efficiency between areas of the set was
47.5 percent, which indicates that users were generally able to
reach their destinations without excessive detours.
The success of Animotus with untrained users in “Flatland” left
Spiers optimistic about future developments and applications for
his device. If connected to GPS rather than indoor navigational
targets, perhaps the device will be able to guide users outdoors
wherever they choose to go. Of course, this introduces a host of
safety hazards that did not exist in the controlled atmosphere of
“Flatland,” but Spiers believes that with some training, visually
impaired users may one day be able to confidently navigate
outdoor streets with the help of an Animotus.
Spiers is particularly encouraged by emails he has received
from members of the visually impaired community, thanking
him for his research on this subject and urging him to continue
work on this project. “It’s very rewarding to know that you’re
giving back to society, and that people care about what you’re
doing,” Spiers said.
Though the majority of Spiers’ work has been in the realm
of assistive technologies for the visually impaired, he has also
worked to develop surgical robots to allow doctors to remotely
feel tissues and organs without actually touching them.
Spiers cautions students who focus exclusively on one area
of study, as he would not have accomplished what he has with
the Animotus without an awareness of what was going on in a
variety of fields. Luckily, for budding professionals in all fields,
opportunities for collaborations akin to Spiers’ with Extant have
never been more abundant.
November 2015
9

NEWS
health
LESSONS FROM THE HADZA
Modern hunter-gatherers reveal energy use strategies
BY JONATHAN GALKA
The World Health Organization attributes obesity in
developed countries to a decrease in exercise and energy
expenditure compared to our hunter-gatherer ancestors, who
led active lifestyles. In recent research, Yale professor Brian
Wood examined total energy expenditure and metabolism in
the Hadza population of northern Tanzania — a society of
modern hunter-gatherers.
The Hadza people continue traditional tactics of hunting
and gathering. Every day, they walk long distances to
forage, collect water and wood, and visit neighboring
groups. Individuals remain active well into middle age. Few
populations today continue to live an authentic huntergatherer
lifestyle. This made the Hadza the perfect group
for Wood and his team to research total energy expenditure,
or the number of calories the body burns per day, adjusted
for individuals who lead sedentary, moderate intensity, or
strenuous lives. This total energy expenditure is a vital metric
used to determine how much energy intake a person needs.
The researchers examined the effects that body mass, fatfree
mass, sex, and age have on total energy expenditure.
They then investigated the effects of physical activity and
daily workload. Finally, they looked at urinary biomarkers
of metabolic stress, which reflect the amount of energy the
body needs to maintain normal function.
Wood was shocked by the results he saw. Conventional
public health wisdom associates total energy expenditure
with physical activity, and thus blames lower exercise rates
for the western obesity epidemic. But his study found that
fat-free mass was the strongest predictor of total energy
expenditure. Yes, the Hadza people engage in more physical
activity per day than their western counterparts, but when
the team controlled for body size, there was no difference
in the average daily energy expenditure between the two
groups. “Neither sex nor any measure of physical activity or
workload was correlated with total energy expenditure in
analyses for fat-free mass,” Wood said.
Moreover, despite their similar total energy expenditure,
Hadza people showed higher levels of metabolic stress
compared to people in western societies today. The overall
suggestion that this data seemed to be making was that
there is more to the obesity story than a decline in physical
exercise. Wood and his colleagues have come up with an
alternative explanation.
“Adults with high levels of physical activity may adapt by
reducing energy allocation to other physical activity,” Wood
said.
It would make sense, then, that total energy expenditure
is similar across wildly different lifestyles — people who
participate in strenuous activity every day reorganize their
energy expenditure so that their total calories burned stays
in check.
To account for the higher levels of metabolic stressors
in Hadza people, Wood and his research team suggested
high rates of heavy sun exposure, tobacco use, exposure to
smoke from cooking fires, and vigorous physical activity, all
characteristic of the average Hadza adult.
Daily energy requirements and measurements of physical
activity in Hadza adults demonstrate incongruence with
current accepted models of total energy expenditure: despite
their high levels of daily activity, Hadza people show no
evidence of a greater total energy expenditure relative to
western populations.
Wood said that further work is needed in order to
determine if this phenomenon is common, particularly
among other traditional hunter-gatherers.
“Individuals may adapt to increased workloads to keep
energy requirements in check,” he said, adding that these
adaptations would have consequences for accepted models
of energy expenditure. “Particularly, estimating total energy
expenditure should be based more heavily on body size and
composition and less heavily on activity level.”
Collaborators on this research project included Herman
Pontzer of Hunter College and David Raichlen of the
University of Arizona.
IMAGE COURTESY OF BRIAN WOOD
Three hunter-gatherers who were subjects of Wood’s study
stand overlooking the plains of Tanzania, home to the Hadza
population.
10 November 2015

cell biology
NEWS
THE PROTEIN EXTERMINATORS
PROTACs offer alternative to current drug treatments
BY KEVIN BIJU
IMAGE COURTESY OF YALE UNIVERSITY
Craig Crews, Yale professor of chemistry, has developed a
variation on a class of proteins called PROTACs, which destroy
rogue proteins within cancerous cells. Crews has also founded
a company to bring his treatment idea closer to industry.
Your house is infested with flies. The exterminators try
their best to eliminate the problem, but they possess terribly
bad eyesight. If you had the chance to give eyeglasses to the
exterminators, wouldn’t you?
In some ways, cancer is similar to this insect quandary.
A cancerous cell often becomes infested with a host of
aberrant proteins. The cell’s exterminators, proteins called
E3 ubiquitin ligases, then attempt to destroy these harmful
variants, but they cannot properly identify the malevolent
proteins. The unfortunate result: both beneficial and
harmful proteins are destroyed.
How can we give eyeglasses to the E3 ubiquitin ligases?
Craig Crews, professor of chemistry at Yale University, has
found a promising solution.
According to the National Cancer Institute, some 14
percent of men develop prostate cancer during their lifetime.
This common cancer has been linked to overexpression and
mutation of a protein called the androgen receptor (AR).
Consequently, prostate cancer research focuses on reducing
AR levels. However, current inhibitory drugs are not specific
enough and may end up blocking the wrong protein.
Crews and his team have discovered an alternative. By
using PROTACs (proteolysis targeting chimeras), they have
been able to reduce AR expression levels by more than 90
percent.
“We’re hijacking E3 ubiquitin ligases to do our work,”
Crews said.
PROTACs are heterobifunctional molecules: one end
binds to AR, the bad protein, and the other end binds to
the E3 ligase, the exterminator. PROTACs use the cell’s own
quality-control machinery to destroy the harmful protein.
Crews added that PROTACs are especially promising
because they are unlikely to be needed in large doses. “The
exciting implication is we only need a small amount of the
drug to clear out the entire rogue protein population,” he
said. A lower required dose could lessen the risk of negative
side effects that accompany any medication. It could also
mean that purchasing the drug is economcally feasible for
more people.
To put his innovative research into action, Crews founded
the pharmaceutical company Arvinas. Arvinas and the
Crews Lab collaborate and research the exciting potential
of PROTACs in treating cancer. PROTACs have been
designed to target proteins associated with both colon and
breast cancer.
In addition to researching PROTACs, Crews has
unearthed other techniques to exterminate proteins.
“What I wanted to do is take a protein [AR] and add a
little ‘grease’ to the outside and engage the cell’s degradation
mechanism,” Crews said. This grease technique is called
hydrophobic tagging and is highly similar to PROTACs
in that it engages the cell’s own degradation machine to
remove the harmful protein.
Having been given eyeglasses to the E3 ligases, Crews is
looking for new ways to optimize his technique.
“My lab is still trying to fully explore what is possible with
this technology,” he said. “It’s a fun place to be.”
IMAGE COURTESY OF WIKIPEDIA
Enzymes work with ubiquitin ligases to degrade aberrant
proteins in cells.
November 2015
11

NEWS
immunology
MOSQUITOES RESISTANT TO MALARIA
Scientists investigate immune response in A. gambiae
BY JULIA WEI
Anopheles gambiae is professor Richard Baxter’s insect of
interest, and it is easy to see why: The mosquito species found
in sub-Saharan Africa excels at transmitting malaria, one of
the deadliest infectious diseases. “[Malaria] is a scourge of the
developing world,” said Baxter, a professor in Yale’s chemistry
department. Discovering a cure for malaria starts with
understanding its most potent carrier.
This is one research focus of the Baxter lab, where scientists
are probing the immune system of A. gambiae mosquitoes
for answers. Despite being ferocious in their transmission of
malaria to human populations, these insects show a remarkable
immunity against the disease themselves. With ongoing research
and inquiry, scientists could one day harness the immune power
of these mosquitoes to solve a global health crisis — rampant
malaria in developing countries.
The story of Baxter’s work actually starts with a 2006 study, a
pioneering collaboration led by professor Kenneth Vernick at
the University of Minnesota. Vernick and his team collected and
analyzed samples of this killer bug in Mali. The researchers were
surprised by what they found. Not only did offspring infected with
malaria-positive blood carry varying numbers of Plasmodium,
the parasite responsible for transmitting malaria, but a shocking
22 percent of the mosquitos sampled carried no parasite at all.
Since then, scientists have turned their attention to the complex
interplay between malaria parasites and A. gambiae’s immune
system. Vernick’s group correlated the mosquitos’ genomes with
their degree of parasite infection, and identified the gene cluster
APL1 as a significant factor in the insect’s ability to muster an
immune response.
Now, nearly a decade following Vernick’s research in Mali,
A. gambiae’s immune mechanism is better understood. Three
proteins are key players in the hypothesized immune chain of
response: APL1, TEP1, and LRIM1. TEP1 binds directly to
malaria parasites, which are then destroyed by the mosquito’s
immune system. Of course the molecule cannot complete the job
alone. TEP1 only works in combatting infection when a complex
of LRIM1 and APL1 is present in the mosquito’s blood and is
available as another line of defense.
To complicate matters, this chain of response is a mere outline
for the full complex mechanism. Gene cluster APL1 codes for
three homologous proteins named APL1A, APL1B, and APL1C.
According to Baxter, this family of proteins may serve as “a
molecular scaffold” in the immune response. Though they all
belong to the APL1 family, each individual protein may serve a
distinct purpose within A. gambiae’s immune system. Herein lies
one of Baxter’s goals — uncover the functions and mechanisms of
the individual proteins.
Prior research has elucidated the role of protein C in this
family. Scientists have observed that LRIM1 forms a complex
with APL1C, and this complex then factors in to the immune
response for the mosquito. How proteins A and B contribute to
the immune response was poorly understood.
In Baxter’s lab, confirming whether LRIM1 forms similar
complexes with APL1A and APL1B posed a challenge, namely
because both proteins are unstable. Through trial and error,
Baxter’s team found that LRIM1 does indeed form complexes
with APL1A and APL1B. The scientists also observed modest
binding to TEP1, the protein that attaches itself directly to the
malaria parasite. This finding could further explain how the
mosquito’s immune system is able to put up such a strong shield
against malaria.
Within the APL1 family, the APL1B protein still presents the
most unanswered questions. Previous studies have shown that
APL1A expression leads to phenotypes against human malaria,
and APL1C to phenotypes against rodent malaria. The role of
APL1B remains cloudy. “Being contrarian people, we decided
to look at the structure of APL1B because it’s the odd one out,”
Baxter said.
His lab discovered that purified proteins APLIA and APL1C
remain monomers in solution, while APL1B becomes a
homodimer, two identical molecules linked together. Brady
Summers, a Yale graduate student, went on to determine the
crystal structure of APL1B.
This focus on tiny molecules is all motivated by the overarching,
large-scale issue of malaria around the globe. The more
information that Baxter and other scientists can learn in the lab,
the closer doctors will be to reducing the worldwide burden of
malaria.
“Vast amounts of money are spent on malaria control, but
our methods and approaches have not changed a lot and are
susceptible to resistance by both the parasite and the mosquito
vector,” Baxter said. A better understanding of A. gambiae in
the lab is the first step towards developing innovative, effective
measures against malaria in medical practice.
IMAGE COURTESY OF RICHARD BAXTER
The APL1B protein, here in a homodimer, remains elusive.
12 November 2015

BLACK HOLE
WITH A GROWTH
PROBLEM
a supermassive black hole
challenges foundations
of modern astrophysics
by Jessica Schmerler
art by Ashlyn Oakes

A long, long time
ago in a galaxy far,
far away…
the largest black holes discovered to
date was formed. While working on a
project to map out ancient moderate-
of international researchers stumbled
across an unusual supermassive black
hole (SMBH). This group included
Munson professor of astrophysics.
was surprised to learn that certain
qualities of the black hole seem to
challenge widely accepted theories
about the formation of galaxies.
The astrophysical theory of co-evolution
suggests that galaxies pre-date their
black holes. But certain characteristics
of the supermassive black hole located in
CID-947 do not fit this timeline. As Urry
put it: “If this object is representative [of the
evolution of galaxies], it shows that black
holes grow before their galaxies — backwards
from what the standard picture says.”
The researchers published their remarkable
findings in July in the journal Science. Not only
was this an important paper for astrophysicists
everywhere, but it also reinforced the mysterious
nature of black holes. Much remains unknown
about galaxies, black holes, and their place
in the history of the universe — current theories
may not be sufficient to explain new observations.
The ordinary and the supermassive
Contrary to what their name might suggest,
black holes are not giant expanses of empty space.
They are physical objects that create a gravitational
field so strong that nothing, not even light, can escape.
As explained by Einstein’s theory of relativity,
black holes can bend the fabric of space and time.
An ordinary black hole forms when a star reaches
the end of its life cycle and collapses inward — this
sparks a burst of growth for the black hole as it absorbs
surrounding masses. Supermassive black holes,
on the other hand, are too large to be formed by a single
star alone. There are two prevailing theories regarding
their formation: They form when two black
holes combine during a merging of galaxies, or they are
generated from a cluster of stars in the early universe.
If black holes trap light, the logical question that follows is
how astrophysicists can even find them. The answer: they find
them indirectly. Black holes are so massive that light around
them behaves in characteristic, detectable ways. When orbiting
masses are caught in the black hole’s gravitational field,
they accelerate so rapidly that they emit large amounts of radiation
— mainly X-ray flares — that can be detected by special
telescopes. This radiation appears as a large, luminous circle
known as the accretion disc around the center of the black hole.
Active galactic nuclei are black holes that are actively forming,
and they show a high concentration of circulating mass in their
accretion discs, which in turn emits high concentrations of light.
The faster a black hole is growing, the brighter the accretion disc.
With this principle in mind, astrophysicists can collect relevant information
about black holes, such as size and speed of formation.
The theory of co-evolution
Nearly all known galaxies have at their center a moderate to supermassive
black hole. In the mid-1990s, researchers began to notice
that these central black holes tended to relate to the size and shape of

astronomy
FOCUS
their host galaxies. Astrophysicists proposed
that galaxies and supermassive
black holes evolve together, each one
determining the size of the other. This
idea, known as the theory of co-evolution,
became widely accepted in 2003.
In an attempt to explain the underlying
process, theoretical physicists have proposed
that there are three distinct phases of
co-evolution: the “Starburst Period,” when
the galaxy expands, the “SMBH Prime
Period,” when the black hole expands,
and the “Quiescent Elliptical Galaxy,”
when the masses of both the galaxy and
the black hole stabilize and stop growing.
The supermassive black hole at the center
of the galaxy CID-947 weighs in at seven
billion solar masses — seven billion times
the size of our sun (which, for reference, has
a radius 109 times that of the earth). Apart
from its enormous size, what makes this
black hole so remarkable are the size and
character of the galaxy that surrounds it.
Current data from surveys observing
galaxies across the universe indicates that
the total mass distributes between the
black hole and the galaxy in an approximate
ratio of 2:1,000, called the Magorrian
relation. A typical supermassive black
hole is about 0.2 percent of the mass of its
host galaxy. Based on this mathematical
relationship, the theory of co-evolution
predicts that the CID-947 galaxy would
be one of the largest galaxies ever discovered,
but in reality CID-947 is quite ordinary
in size. This system does not come
close to conforming to the Magorrian relation,
as the central black hole is a startling
10 percent of the mass of the galaxy.
An additional piece of the theory of
co-evolution is that the growth of the
supermassive black hole prevents star
formation. Stars form when extremely
cold gas clusters together, and the resultant
high pressure causes an outward
explosion, or a supernova. But when
a supermassive black hole is growing,
the energy from radiation creates a tremendous
amount of heat — something
that should interrupt star formation.
Here, CID-947 once again defies expectations.
Despite its extraordinary size, the
supermassive black hole did not curtail the
creation of new stars. Astrophysicists clearly
observed radiation signatures consistent
with star formation in the spectra captured
IMAGE COURTESY OF WIKIMEDIA COMMONS
The W.M. Keck Observatory rests at the
summit of Mauna Kea in Hawaii.
at the W.M. Keck Observatory in Hawaii.
The discovery of the CID-947 supermassive
black hole calls into question
the foundations of the theory of co-evolution.
That stars are still forming indicates
that the galaxy is still growing,
which means CID-947 could eventually
reach a size in accordance with the Magorrian
relation. Even so, the evolution of
this galaxy still contradicts the theory of
co-evolution, which states that the growth
of the galaxy precedes and therefore dictates
the growth of its central black hole.
New frontiers in astrophysics
Astrophysicists are used to looking
back in time. The images in a telescope
are formed by light emitted long before
the moment of observation, which means
the observer views events that occurred
millions or even billions of years in the
past. To see galaxies as they were at early
epochs, you would have to observe them
at great distances, since the light we see
today has traveled billions of years, and
was thus emitted billions of years ago.
The team of astrophysicists that discovered
the CID-947 black hole was observing
for two nights at the Keck telescope in order
to measure supermassive black holes in active
galaxies as they existed some 12 billion
years ago. The researchers did not expect
to find large black holes, which are rare
for this distance in space and time. Where
they do exist, they usually belong to active
galactic nuclei that are extremely bright.
But of course the observers noticed the
CID-947 supermassive black hole, which
is comparable in size to the largest black
holes in the local universe. Its low luminosity
indicates that it is growing quite slowly.
“Most black holes grow with low accretion
rates such that they gain mass slowly.
To have this big a black hole this early
in the universe means it had to grow very
rapidly at some earlier point,” Urry said.
In fact, if it had been growing at the observed
rate, a black hole this size would
have to be older than the universe itself.
What do these contradictions mean for
the field of astrophysics? Urry and her
colleagues suggest that if CID-947 does in
fact grow to meet the Magorrian relation
relative to its supermassive black hole, this
ancient galaxy could be a model for the
precursors of some of the most massive
galaxies in the universe, such as NGC 1277
of the Perseus constellation. Moreover, this
research opens doors to better understanding
black holes, galaxies, and the universe.
ABOUT THE AUTHOR
JESSICA SCHMERLER
JESSICA SCHMERLER is a junior in Jonathan Edwards College majoring
in molecular, cellular, and developmental biology. She is a member of the
magazine, and contributes to several on-campus publications.
enthusiasm about this fascinating discovery.
Cambridge University Press, 2004.
November 2015
15

FOCUS
biotechnology
By Emma Healy • Art by Christina Zhang
What constitutes a protein? At
first, the answer seems simple
to anyone with a background
in basic biology. Amino acids join together
into chains that fold into the unique
three-dimensional structures we call proteins.
Size matters in proteomics, the scientific
study of proteins. These molecules
are typically complex, comprised of hundreds,
if not thousands, of amino acids.
A protein with demonstrated biological
function usually contains no fewer than
300 amino acids. But findings from a recent
study conducted at the Yale School of
Medicine are challenging the notion that
proteins need to be long chains in order
to serve biological roles. Small size might
not be an end-all for proteins.
The recent research was headed by the
laboratory of Yale genetics professor Daniel
DiMaio. First author Erin Heim, a PhD
student in the lab, and her colleagues conducted
a genetic screen to isolate a set of
functional proteins with the most minimal
set of amino acids ever described.
The chains are short and simple, yet they
exert power over cell growth and tumor
formation. Few scientists would have predicted
that such simple molecules could
have such huge implications for oncology,
and for our basic understanding of proteins
and amino acids.
Engineering the world’s simplest
proteins
There are 20 commonly cited amino acids,
and their order in a chain determines
the structure and function of the resulting
protein. Most proteins consist of many different
amino acids. In contrast, the proteins
identified in this study, aptly named
LIL proteins, were made up entirely of two
amino acids: leucine and isoleucine.
Both of these amino acids are hydrophobic,
meaning they fear water. The scientists
at DiMaio’s lab were deliberately searching
for hydrophobic qualities in proteins. An
entirely hydrophobic protein is limited in
where it can be located within the cell and
what shapes it can assume. To maintain a
safe distance from water, a hydrophobic
protein would situate itself in the interior
of a cell membrane, protected on both
sides by equally water-fearing molecules
called lipids. Moreover, the hydrophobic
property reduces protein complexity by
limiting the potential for interactions between
the polar side chains of hydrophilic,
or water-loving, amino acids. These polar
side chains are prone to electron shuffling
and other modifications, adding considerable
complexity to the protein’s function.
Heim and her group wanted to keep
things simple — a protein that is completely
hydrophobic is more predictable, and is
thus easier to investigate as a research focus.
“It’s rare that a protein is composed
entirely of hydrophobic amino acids,” said
Ross Federman, another PhD student in
the DiMaio lab and another author on the
recent paper.
The LIL proteins were rare and incredibly
valuable. “[Using these proteins] takes
away most of the complication by knowing
where they are and what they look like,”
Heim said. In terms of both chemical reactivity
and amino acid composition, she
said the LIL proteins truly are the simplest
to be engineered to have a biological function.
Small proteins, big functions
What was the consequential biological
function? Through their research, the
scientists were able to link their tiny LIL
proteins to cell growth, proliferation, and
cancer.
The team started with a library of more
than three million random LIL sequences
and incorporated them into retroviruses,
or viruses that infect by embedding their
viral DNA into the host cell’s DNA. “We
manipulate viruses to do our dirty work,
essentially,” Heim said. “One or two viruses
will get into every single cell, integrate
into the cell’s DNA, and the cell will make
that protein.”
16 November 2015

proteomics
FOCUS
As cells with embedded viral DNA started
to produce different proteins, the researchers
watched for biological functions.
In the end, they found a total of 11
functional LIL proteins, all able to activate
cell growth.
Of course this sounds like a good thing,
but uncontrolled cell growth can cause a
proliferation of cancerous cells and tumors.
The LIL proteins in this study affected
cell growth by interacting with the
receptor for platelet-derived growth factor
beta, or PDGFβ. This protein is involved
in the processes of cell proliferation, maturation,
and movement. When the PDG-
Fβ receptor gene is mutated, the protein’s
involvement in cell growth is derailed, resulting
in uncontrolled replication and tumor
formation. By activating the PDGFβ
receptor, the LIL proteins in this study
grant cells independence from growth factor,
meaning they can multiply freely and
can potentially transform into cancerous
cells.
While this particular study engineered
proteins that activated PDGFβ, Heim said
that other work in the lab has turned similar
proteins into inhibitors of the cancer-causing
receptor. By finding proteins
to block activation of PDGFβ, it may be
possible to devise a new method against
one origin of cancer. Even though the biological
function in their most recent paper
was malignant, Heim and her group are
hopeful that these LIL proteins can also be
applied to solve problems in genetics.
Reevaluating perceptions of a protein
No other protein is known to exist with
sequences as simple as those within the
LIL molecules. Other mini-proteins have
been discovered, but none on record have
been documented to display biological activity.
For example, Trp-cage was previously
identified as the smallest mini-protein
in existence, recognized for its ability to
spontaneously fold into a globular structure.
Experiments on this molecule have
been designed to improve understanding
of protein folding dynamics. While Trpcage
and similar mini-proteins serve an
important purpose in research, they do
not measure up to LIL proteins with regard
to biological function.
The recent study at the DiMaio lab pursued
a question beyond basic, conceptual
science: The team looked at the biological
function of small proteins, not just their
physical characteristics.
The discovery of LIL molecules and the
role they can play has significant implications
for the way scientists think about
proteins. In proteomics, researchers do
not usually expect to find proteins with
extraordinarily short or simple sequences.
For this reason, these sequences tend
to be overlooked or ignored during genome
scans. “This paper shows that both
[short and simple proteins] might actually
be really important, so when somebody is
scanning the genome and cutting out all
of those possibilities, they’re losing a lot,”
Heim said.
Additionally, by limiting the amino acid
diversity of these proteins, researchers
were able to better understand the underlying
mechanisms of amino acid variation.
“If you want to gain insight into the heart
of some mechanism, the more you can isolate
variables, the better your results will
be,” Federman said.
This is especially true for proteins. These
molecules are highly complex, possessing
different energetic stabilities, varying conformations,
and the potential for substantial
differences in amino acid sequence. By
studying LIL proteins, researchers at the
DiMaio lab were able to isolate the effects
of specific amino acid changes at the molecular
level. This is critical information
for protein engineers, who tend to view
most hydrophobic amino acids similarly.
This study contradicted that notion: “Leucine
and isoleucine have very distinct activities,”
Heim said. “Even when two amino
acids look alike, they can actually have
very dissimilar biology.”
Daniel DiMaio is a professor of genetics at
the Yale School of Medicine.
Another ongoing project at the lab involves
screening preexisting cancer databases
in search of short-sequence proteins.
According to Heim, it is possible that scientists
will eventually find naturally occurring
cancers containing similar structures
to the LIL proteins isolated in this
study. This continuing study would further
elucidate the cancer-causing potential
of tiny LIL molecules.
To take their recent work to the next
step, researchers in this group are looking
to create proteins with functions that did
not arise by evolution. The ability to build
proteins with entirely new functions is an
exciting and promising prospect. It presents
an entirely new way of approaching
protein research. The extent of insight into
proteins is no longer bound by the trajectory
of molecular evolution. Instead, scientific
knowledge of proteins is being expanded
daily in the hands of researchers
like Heim and Federman.
November 2015
IMAGE COURTESY OF YALE SCHOOL OF MEDICINE
ABOUT THE AUTHOR
EMMA HEALY
EMMA HEALY is a sophomore in Ezra Stiles college and a prospective
molecular, cellular, and developmental biology major.
THE AUTHOR WOULD LIKE TO THANK the staff at the DiMaio laboratory,
with a special thanks to Erin Heim and Ross Federman for their time and
enthusiasm.
FURTHER READING
Cammett, T. J., Jun, S. J., Cohen, E. B., Barrera, F. N., Engelman, D. M., &
DiMaio, D. (2010). Construction and genetic selection of small transmembrane
proteins that activate the human erythropoietin receptor. Proceedings of the
National Academy of Sciences, 107(8), 3447-3452.
17

FOCUS biotechnology
EAST MEETS WEST IN CANCER TREATMENT
Ancient herbal remedies prove their worth in clinical trials
By Milana Bochkur Dratver
Art By Alex Allen
Does grandma’s chicken soup really
chase a cold away? Do cayenne and
lemon really scare away a sore throat?
Some doctors and scientists are skeptical of
old wives’ tale remedies, and some of this
skepticism is justified. But Yung-Chi Cheng
advocates for an open-minded approach to
medical treatment. The end goal, after all, is
to give patients the best care possible, and
that means no potential treatment should be
overlooked.
Had Cheng been close-minded to eastern
medicine, ignoring remedies from ancient
China, he would not have come across a new
drug with exciting promise for cancer therapy.
With PHY906 — a four-herb recipe that for
2,000 years treated diarrhea, nausea, and
vomiting in China — Cheng is transforming
the paradigm of cancer treatment. Cancer is
a relatively modern medical condition, but
cancer treatments could use some support
from traditional recipes.
Cheng is a Henry Bronson professor of
pharmacology at the Yale School of Medicine.
Members of his lab have standardized the
PHY906 concoction, emphasizing good
manufacturing practice to circumvent some
of the criticisms of traditional herbal remedies.
In 2003, Cheng started the Consortium
for the Globalization of Chinese Medicine,
linking 147 institutions and 18 industrial
companies. “It is the biggest non-political
nonprofit with no bias or discrimination in
promoting traditional medicine,” Cheng said.
The story of Cheng’s career showcases this
belief in learning from some of the earliest
approaches to fixing human ailments.
PHY906 is currently awaiting FDA approval,
but researchers at multiple institutions across
the country are collecting data to support
its effectiveness. Results so far have been
promising: this herbal remedy seems not only
to diminish the nasty side effects of cancer
treatments, but enhances the efficiency of the
treatments as well.
Passing tests with flying colors
PHY906 is based on the historic Huang
Qin Tang formula, pronounced “hwong chin
tong.” The four ingredients are Chinese peony,
Chinese jujube, baikal skullcap, and Chinese
licorice. Some of the strongest evidence has
come out of studies in mouse models, which
show that all four ingredients are necessary in
order for PHY906 to be maximally effective.
When any one ingredient was left out, the
recipe was not as successful in treating mice
with liver cancer.
Even without the tools of modern scientific
research at their disposal, healers in ancient
China devised a scientifically sound solution
for a health problem. Cheng and his colleagues
support the examining of many different types
of historical texts for cultural remedies. Despite
scientific advancement, researchers can still
learn from the past.
Still, scientists want more than an interesting
idea grounded in history and culture — they
expect reproducible and quantifiable results.
PHY906 has so far measured up to the stringent
standards of modern research. The experiment
in mice used PHY906 in combination with
Sorafenib, the only FDA-approved drug for
the treatment of this specific liver cancer. Not
only did the addition of PHY906 decrease
unwanted side effects, but it also enhanced the
efficacy of Sorafenib.
Ongoing research involves deciphering if
PHY906 produces similar results in treating
other cancers and in different treatment
combinations. The drug is proceeding through
several levels of clinical trials as it seeks
FDA approval for human use. This involves
testing the compound in combination with
other conventional cancer therapies, such as
radiation treatment.
The ultimate goal is to bring PHY906 to
the U.S. as a prescription drug to supplement
chemotherapy, which is notorious for its
terrible side effects.
Early inspiration
Cheng has long been interested in side
effects, and in ways to eliminate them. His
independent scientific career began in 1974,
when he investigated viral-specified replication
systems. At the time, few people thought there
would be a way to selectively target viruses using
specialized compounds, but this soon became a
reality. Using the herpes virus as a model system,
Cheng found that virus-specific proteins could
in fact be susceptible to healing agents. That is,
you could introduce a compound that targets
viruses without harming other cells in its wake.
Less than a decade later, Cheng discovered
a compound to combat cytomegalovirus, a
major cause of infant mortality. The same
compound worked to treat people infected
with HIV in the 1980s. This breakthrough
in treatments for viral diseases motivated
many scientists to search for drug-based
treatments for a variety of health conditions,
including cancer. (In fact, this was the point
when medicine saw the early development
of cancer drugs.) The new drug compounds
were effective in targeting diseases, but they
simultaneously caused detrimental side effects.
The question that followed was how to
eliminate negative side effects without reducing
the beneficial effects of a drug. Cheng decided
to probe the mechanism of action of these
drugs. He found that side effects stemmed
from toxification of the mitochondria —
these organelles are energy powerhouses, and
they were suffering damage and declining in
number. Cheng’s findings made the next step in
drug development exceedingly clear: treating
diseases would require a targeted approach,
one that attacked the disease-causing agents
but kept all other cell parts working normally.
When he zoomed in his focus on cancer,
Cheng realized it was unlikely that a single
chemical would be sufficient. Cancerous
tissue is heterogeneous, which means one
compound is unlikely to affect an entire
18 March 2015

medicine
FOCUS
population of cancer cells. “It was clear that
a new paradigm needed to be developed
as to how to fundamentally address cancer
treatment,” Cheng said.
His solution was to turn to the human body’s
immune system, which shifted the focus from
treating cancer from without to exploiting the
body’s own internal mechanisms of healing
and defense.
With this more holistic view of cancer,
Cheng thought that multiple targeting agents
would be needed in combination, since it was
improbable that one compound would succeed
on its own in killing the mixed cancer tissue.
Identical treatments often had varying degrees
of effectiveness in different patients, leading
Cheng to look to historical medical practices
for clues that would hint at better treatment
options. While reading about ancient remedies
still in use today, Cheng discovered that
Chinese medicine had been using the multiple
target approach for generations.
Armed with this insight, he investigated
roughly 20 herbal combinations that are
still in use but have ancient roots. These
home remedies have been used to address
symptoms such as diarrhea and nausea, and
Cheng believed they could also prove useful
in reducing the side effects of cancer treatment
without disturbing the important work of
chemotherapy.
Mechanism behind the magic
Cheng’s lab is also working to understand
why and how the combination of herbs in
PHY906 is so effective. Current data points to
two primary mechanisms.
The first proposal suggests that the recipe
works as an inflammation inhibitor. All three
major inflammatory pathways in the body
seem to be affected by the presence of PHY906,
suggesting that the herbs have multiple sites
of action within the body. By addressing all
three pathways, the results of PHY906 are
better than any anti-inflammatory drug on the
market today.
Interestingly, there was one class of
ancient Chinese diseases that translates to
“heat.” Diseases in this subset were related to
inflammation. When traditional remedies
prescribed to treat “heat” diseases were
screened against six well-characterized
inflammation pathways, more than 80 percent
of the herbs in this treatment category showed
activity against at least one pathway. When
a different class of herbs was tested against
inflammatory pathways, only 20 percent
showed any relation. The oral tradition seems
to correlate with strong scientific results.
The other mechanism of action for PHY906
could be that the herbal combination enhances
the recovery of damaged tissue by increasing
the rate of propagation for stem cells and
progenitor cells. Both cells tend to differentiate
into different target cell types depending on
what is needed. By activating the expression of
genes in charge of the stem cell and progenitor
cell pathways, PHY906 can accelerate the
proliferation of new cells to fix damaged tissue.
These scientific suggestions for the magic
behind PHY906 offer some hope that the drug
could one day be applied to treat other diseases
besides cancer. In keeping inflammation in
check, for example, the ancient herbal remedy
could prove useful in mitigating symptoms of
colon inflammatory disease.
Bridging the East-West gap
Another significant impact of PHY906, one
that Cheng hopes continues growing in the
future, is its role in the convergence of modern
and traditional medicine. An integrative
approach to treatment considers all options
and explores the potential of compounds
new and old. Cheng’s work is one example of
a shift in perspective that may be essential in
unlocking mysteries of modern medicine.
Traditional remedies cannot be discounted.
They would not have survived generations
without proving efficacy time and time
again. As medicine is forced to confront
increasingly complicated diseases — from
neurodegeneration, to diabetes, to metabolic
syndromes — it is imperative that medical
professionals explore all avenues, including
those that already exist but need to resurface.
“The etiology of these complex syndromes
and illnesses is not singular; they are caused
by many different genetic and environmental
factors,” Cheng said. “Thus, it is impractical to
[have a singular focus] as we pursue solutions.”
There are certainly concerns to be raised
over the application of ancient home remedies
in medical practice, but Cheng’s lab keeps all
research up to stringent standards. The team
operates under good manufacturing practice,
ensuring that each batch of PHY906 maintains
the same chemical properties. One of the key
issues with natural medicine is deviation in
ingredients — each is grown from the earth
and not in the lab, which means it may have
a slightly different chemical composition every
time it is used. Good manufacturing practice is
a precise process that specifies exact minutes,
concentrations, and temperatures for each step
in drug development.
What makes Cheng’s product unique is
that no other pharmacological institution has
created such precise rules and regulations for
the manufacture of a traditional remedy.
And it is a remedy he truly believes in. “It is
our job to figure out the right combinations
to solve our problems,” Cheng said. PHY906
could be a leap forward in cancer treatment,
and it only came to light through openminded
research. Cheng’s Consortium for the
Globalization of Chinese Medicine emphasizes
collaboration. Consortium members come
together in dealing with the challenges of
working with traditional treatments and share
quality control regulations as well as sources of
herbs.
Cheng is devoted to PHY906 and to
integrating eastern medical remedies with
western research practices. “Moving forward,”
he said, “scientists need to take advantage of
the naturally occurring library of chemicals
that Mother Nature has provided us.”
ABOUT THE AUTHOR
MILANA BOCHKUR DRATVER
MILANA BOCHKUR DRATVER is a sophomore mollecular, cellular, and
developmental biology major in Jonathan Edwards College. She serves
as the volunteer coordinator for Synapse.
THE AUTHOR WOULD LIKE TO THANK professor Cheng for his time
and enthusiasm about sharing his research.
FURTHER READING
Lam, et al. “PHY906(KD018), an Adjuvant Based on a 1800-year-old Chinese
Medicine, Enhanced the Anti-tumor Activity of Sorafenib by Changing the
November 2015
19

Nature's
BLUEPRINT
BY GENEVIEVE SERTIC
Solar cells inspired by plant cells
Art by Chanthia Ma
At first glance, nature and technology
may seem like opposites. Leaves
stand in contrast to circuits, birds to
airplanes, and mountains to skyscrapers. But
technology has a history of taking cues from
nature. Velcro was inspired by burdock burrs,
while aircraft were modeled after bird wings.
The Shinkansen Bullet Train was constructed
with the kingfisher’s beak in mind. A closer
lens on nature unlocks tremendous potential
for technological innovation, and plant cells
are no exception.
Yale researchers are now looking to plant
cells in order to improve the design of solar
power, touted as a carbon-free alternative energy
source. At the heart of solar power are solar
cells, which, like plant cells, aim to absorb sunlight
and turn it into a useable form of energy.
André Taylor, associate professor of chemical
and environmental engineering, and Tenghooi
Goh, a graduate student in the School of Engineering
and Applied Science, worked with
their team to develop an organic solar cell that
mimics the chemistry of plant cells.
Most solar power today relies on silicon solar
cells, which do not precisely parallel plant
cells. When sunlight hits a silicon solar cell, an
electron jumps across the material and moves
through a wire to generate electricity. Plant
cells instead take the light energy and transfer
it to a protein through a chemical process.
These cells from nature can inform optimal
materials for use in organic solar cells, as the
Yale group discovered. Organic solar cells are
relatively new in the field of solar energy. There
are many different types, but generally speaking,
organic solar cells are lighter, less costly,
and have more environmentally-friendly manufacturing
processes than their traditional silicon
counterparts.
At this point, the choice of a solar cell probably
seems obvious. But organic solar cells come
with one major drawback: efficiency. Solar cell
efficiency refers to the amount of electricity
generated relative to the input of sunlight energy.
While silicon cells have achieved efficiencies
of more than 20 percent, organic cells are
lagging behind.
Taylor and his team sought to increase this
efficiency while maintaining the advantages
of organic solar cells. They blended together
two polymers with complementary properties,
aligning them to make them compatible. Together,
these polymers can absorb light from
much of the visible spectrum, which explains
their greater combined efficiency. The Yale
researchers managed to increase efficiency of
this particular type of solar cell by almost 25
percent.
The key to better solar energy, as it turns out,
lies in nature.
A three-part design
To turn light energy into electrical energy,
organic solar cells need a material that gives up
an electron — a donor — and a material that
takes that electron — an acceptor. However,
the donor polymer can only absorb a certain
range of light wavelengths. Wavelengths outside
of this range are wasted. The recent development
from Yale scientists allows an organic
solar cell to absorb a wider range: Adding another
donor that accepts a different but complementary
range of light wavelengths gets at
the efficiency problem directly.
These new types of solar cells are called ternary
cells, and they have three components:
two donors, one acceptor. Unfortunately, more
often than not, the two donors conflict with
each other and lower the overall efficiency of
energy conversion.
Polymers P3HT and PTB7 are two such incompatible
donors. They align in completely
different directions, with P3HT standing vertically
and PTB7 lying horizontally. In poorly-aligned
structures, charge recombination
occurs, wherein an electron meant to generate
electricity is reabsorbed into a hole in the material,
or a place where an electron could exist
but does not.
But not all hope was lost for P3HT and
PTB7. Taylor’s team noticed that the wavelengths
of light absorbed by the polymers are
in fact complementary — P3HT takes in bluegreen
light, while PTB7 is best at absorbing
light in the yellow-red spectrum. Overcoming
their incompatibility would allow for a much
more efficient ternary cell, and this is exactly
what Taylor’s team set out to do.
Finding agreement in incompatibility
In order to reduce the interference between
the two donor polymers, the team focused on

environmental engineering
FOCUS
a couple methods, including Förster resonance
energy transfer (FRET). FRET is a mechanism
by which two light-sensitive molecules, or
chromophores, transmit energy. This process
helps primarily in biological studies to trace
proteins as they travel through cells. It is also
one of the primary mechanisms in energy
conversion within a plant cell, and in fact, is
one of the reasons that leaves are so efficient
in converting sunlight into chemical energy.
FRET is not a topic normally brought up when
discussing solar technology, however. “It’s been
heavily used in biology, but never in polymer
solar cells,” Taylor said.
In this study, the researchers focused on
FRET between their two chromophores,
polymers P3HT and PTB7. Individually,
the efficiency of each polymer is not
particularly powerful. However, combining
the polymers facilitates FRET
and allows them to complement
each other, resulting in an efficiency
of 8.2 percent — quite high
for a ternary organic solar cell.
Other groups have also
used various polymers in
conjunction, but never in
a way that forces the
polymers to interact.
Taylor’s team combined
P3HT and
PTB7 and created
a collaborationn.
One polymer
picks up emissions
from the
other. “We’re
the first group
to show that you can actually put these components,
these multiple donors, together, and
have them act synergistically,” Taylor said. The
polymers are complementary — one can recover
lost energy from the other, and together,
they can take in a much wider range of light.
This was among the most pivotal findings in
PHOTO BY GENEVIEVE SERTIC
The red solar cell, incorporating P3HT,
absorbs blue-green light, while the blue solar
cell, made using PTB7, best takes in light
from yellow to red on the visible spectrum.
The natural alignment of the two polymers
a single cell.
the Yale study.
To improve efficiency further, the researchers
focused on adjusting the incompatible
alignment of the polymers. Electron flow is impeded
between P3HT and PTB7. “If organics
align in a conflicting way, they will not allow
electrons to flow in a favorable direction,” Goh
said. A second method the team used, called
solvent vapor annealing, can fix that. The researchers
exposed the solar films containing
the incompatible polymers to vapor to help
the structures relax and smooth out. With
this technique on top of the special attention
to FRET, the organic solar cells achieved a remarkable
efficiency of 8.7 percent.
Strategizing for the future
This research is not only significant because
of increased efficiency. It also describes an innovative
process for overcoming mechanical
difficulties within organic solar cells. Even
after Taylor’s improvements to ternary cells,
organic-based solar power does not match the
efficiency of silicon-based solar power. However,
using their methods as a launching pad,
there is great potential to increase efficiency of
organic solar cells even further in the future.
“As people develop newer polymers, they
can use this study as a road map to create higher-efficiency
devices,” Taylor said.
This study shows that polymers labeled as
incompatible can be re-engineered to complement
each other and to increase solar cell efficiency.
It also illustrates that nature’s answers to
technological challenges are as relevant as ever.
Beyond their basic function of turning sunlight
into useable energy, plant and solar cells
might not seem related at first. Plant cells
convert sunlight into chemical energy, while
solar cells convert sunlight into electricity. But
the mechanisms by which plant cells absorb a
wide range of solar radiation are, as it turns out,
readily applicable to the choice of polymers in
organic solar cells. In fact, plant cells provide a
model that the Yale group found to be incredibly
helpful. The story of solar cells inspired by
plant cells introduces not only new technology,
but a new way of thinking about solar cell
efficiency that reflects our natural world.
ABOUT THE AUTHOR
GENEVIEVE SERTIC
GENEVIEVE SERTIC is a sophomore prospective electrical engineering
major and Energy Studies Undergraduate Scholar in Pierson College. She is
a copy editor for this magazine and works through Project Bright to promote
solar power on Yale’s campus.
THE AUTHOR WOULD LIKE TO THANK Dr. André Taylor and Tenghooi
Goh for their time and enthusiasm about their research.
FURTHER READING
Huang, Jing-Shun et al. 2013. “Polymer bulk heterojunction solar cells
employing Förster resonance energy transfer.” Nature Photonics 7: 479-485.
doi: 10.1038/nphoton.2013.82
November 2015
21

Computers master medieval texts
By Amanda Buckingham
Art By Chanthia Ma
Reading a medieval manuscript is like
getting a glimpse at another reality. Like a
window into another time, words written
centuries ago teleport the reader into the past. But
merely looking at words on a page would barely
scratch the surface of all there is to learn from a
medieval manuscript. How did the scribe write?
What inks were used? What is in the foreground,
versus the background? What makes studying
these texts especially challenging is the fact
that worn and aged manuscripts are extremely
delicate.
Bridging the gap between past and present,
however, is a thoroughly modern field: computer
science. Now, by merely opening another sort
of window — a web browser — you can access
millions of digitized images of manuscripts.
Advances in machine learning have allowed
computers to move beyond simply presenting
images of texts to quite literally reading them.
With a tool like optical character recognition,
a computer program can identify text within
images.
Still, computers are not medievalists. Medieval
manuscripts pose a particular problem for
computer-assisted research — the handwriting
style and state of preservation of the text
both limit the accuracy of optical character
recognition. In addition, recording the material
properties of a medieval manuscript is incredibly
time-consuming. The materiality of manuscripts
may obscure text over time, but it also betrays
the secrets of books: how they were made, and
by whom. Scientists and historians alike are thus
interested in discerning material properties of
old texts, and they need efficient, non-invasive
techniques that can handle the sheer size of the
medieval corpus.
To this end, Yale researchers have developed an
algorithm capable of sifting through thousands
of images to discern how many inks were used
in the scribing of each and every page of a
manuscript. Led by Yale professor of computer
science Holly Rushmeier, this project is one
component of an interdisciplinary collaboration
with Stanford University, known as Digitally
Enabled Scholarship with Medieval Manuscripts.
This algorithm in particular is driven by the
fundamental principle of clustering, which
groups pixels into specific categories. It gets at the
number of inks used in individual manuscripts,
but also offers efficiency in analyzing large
databases of images with quickness and accuracy.
While there are other computer platforms relevant
to the topic of medieval manuscripts, most focus
on simple methods such as word spotting and few
can efficiently capture material properties.
The question might seem simple on its surface
— how many colors did this scribe use thousands
of years ago — but the answer is quite telling.
A better understanding of what went into the
creation of medieval manuscripts can reveal
new details about cultures and societies of the
past. Rushmeier’s research takes a technical
approach to history, using computer science
and mathematical formulas to reach conclusions
about medieval texts. She hopes her findings will
aid both scientific and historical scholarship in
22 November 2015

computer science
FOCUS
years to come. Her work stands at the
intersection of science and history, and
tells a compelling story about texts of the
past and programs of the future.
Uncovering a manuscript’s true colors
Scholars have long been interested in
the colors used in medieval manuscripts.
In the past, researchers discerned variations
in the colors used in individual
and small groups of pages. But for an entire
manuscript, or in large comparative
studies, quantifying color usage by visual
inspection is not feasible. Computers, on
the other hand, can wade through thousands
of images without tiring.
Computers can assign values to different
colors, and can then group similar colors
into clusters. The K value, or number
of distinct inks on a page, can then be
determined. For many years, scientists
have been able to manually count
independent inks to obtain approximate
K values. In contrast, the algorithm
developed by Rushmeier’s team is an
automatic method of estimating K, which
is more efficient than prior eyeballing
techniques.
The computer scientists clustered three
types of pixels: decorations, background
pixels, and foreground pixels. Decorations
included foreground pixels that
were not specifically part of text, while
foreground pixels referred to words
written on the page. To test the quality
of their clustering method, namely its
accuracy in determining the number of
inks used per manuscript, the researchers
practiced on 2,198 images of manuscript
pages from the Institute for the Preservation
of Cultural Heritage at Yale.
To evaluate accuracy, the researchers
compared K values produced by the
algorithm to K values obtained manually.
In an analysis of 1,027 RGB images
of medieval manuscripts, which have
red, green, and blue color channels, 70
percent of the initial K values produced
by the computer matched the number
of inks counted manually. When the
value of K was updated after checking
for potential errors, the algorithm’s value
either matched the value determined
by eye or deviated by only one color 89
percent of the time. The scientists were
pleased to see such high accuracy in
their algorithm, and also realized the
importance of updating K to produce
results closer to reality.
Checking for errors is necessary because
even computers make mistakes,
and finding the K value for a medieval
manuscript page is no small feat. For
one, even a single ink color can display
a tremendous amount of variation. The
degradation of organic compounds in
the ink causes variations in the intensity
of pigment to multiply over time. Even
at the time of writing, the scribe could
have applied different densities of ink to
the page. “There’s the potential for seeing
differences that could just be from using
a different bottle of the same ink,” Rushmeier
said.
A computer runs the risk of overestimating
the number of distinct color
groups on a page. Without a proper
check, Rushmeier’s algorithm would produce
a K value higher than what is truly
reflected in the manuscript. Natural
variations in pigment color should not be
construed as separate inks.
What constitutes a cluster?
Medieval manuscripts have a high proportion
of background and foreground
text pixels relative to decorations. Before
the computer carried out clustering,
only the non-text, foreground pixels were
isolated. Differentiating between foreground
and background pixels required a
technique called image binarization. This
was the crucial first step in designing an
algorithm to calculate a K value, according
to postdoctoral associate Ying Yang,
who worked on the project.
The color image of the manuscript
page was converted into a gray scale
that had 256 different color intensities.
The number of pixels for each of the
intensities was sorted into a distribution,
and pixel values within the peak of
the distribution were deemed to be
foreground, while the rest were labeled as
background noise. In the resulting binary
image, foreground pixels were assigned
a zero, while background pixels were
assigned a one.
After the foreground had been differentiated
from the background, text had
to be separated from non-text pixels.
Incidentally, the handwriting in medieval
manuscripts lends itself to this task.
Yang noted that in medieval Western
Europe, text was written in straight bars.
“It’s as if they deliberately tried to make
each letter look like every other letter,”
Rushmeier said. Though this makes computer-assisted
research more difficult in
some respects, the team of Yale scientists
used the similarity of text strokes to their
IMAGE COURTESY OF HOLLY RUSHMEIER
In one step of the Yale study, foreground text pixels were detected and eliminated so that only the non-text pixels remained.
November 2015
23

FOCUS
computer science
These red rectangles indicate text ornamentation that was located and extracted from the images.
IMAGE COURTESY OF HOLLY RUSHMEIER
advantage.
Since the bar-like writing technique
of medieval scribes makes for fairly
uniform letters, the scientists used a resizeable,
rectangular template to match
and identify each pen stroke. First,
they gathered information about text
height and width from the binary image.
Once the size of the template had been
established, it was used to match with
text. Only strokes of a similar size to
the rectangle were given high matching
scores. Since ornately designed capital
letters were not of a similar size compared
to the rest of the text, they received low
matching scores.
Pixels with low matching scores that
were also valued at zero in the binary
image were deemed to be foreground,
non-text pixels that were candidates for
clustering. Once the candidates were
identified, they could finally be classified
into clusters. Of course this method meant
that high matching text was overlooked.
The algorithm had a built-in remedy:
the computer automatically added one
to the total number of clusters derived
from candidate pixels, which resulted
in the initial value of K. This ensured
that the text-cluster, itself representative
of the primary ink used in writing the
manuscript, was counted.
Of course this addition would have
lead to an overestimation of the K value
whenever any text pixels were erroneously
considered candidates for clustering. The
Yale team devised a clever solution to this
problem. The scientists compared the
color data for each of the K clusters with
the color of the text. A striking similarity
between one of these clusters and the
text would indicate that the cluster was
derived from misrouted text pixels.
The color of the text had yet to be
determined. To obtain this piece, the team
performed another round of clustering.
This time, all foreground pixels — text
and non-text — were deemed to be
candidates. Given the large quantity of
text pixels, the text-cluster was fairly easy
to spot. While the only new information
generated in this round of clustering was
the pixel color values of the text-cluster,
this detail was essential in ensuring an
accurate count of inks used on a page.
Importantly, the computer algorithm
had checks in place to add and subtract
from the K value depending on risk of
over or underestimation. It worked efficiently,
but did not sacrifice thoroughness.
In the end, the computer revealed
a well-kept secret of the medieval manuscript
by outputting an accurate value
for K.
The bigger picture
The algorithm was used to analyze
more than 2,000 manuscript images, including
RGB images and multispectral
images, which convey data beyond visible
light in the electromagnetic spectrum.
By calculating K more quickly, this program
offers a more directed research experience.
For example, scholars curious
about decorative elements — say, elaborately
designed initials and line fillers
within a manuscript — can focus on pages
with relatively high K values instead of
spending copious amounts of time filtering
through long lists of manuscripts. In
general, once K has been determined, the
non-text clusters can be used for further
applications. In detecting features such
as ornately drawn capital letters and line
fillers, the team had 98.36 percent accuracy,
which was an incredible, exciting
result.
Though the team is nearing the end of
current allotted funding, provided by the
Mellon Foundation, Rushmeier said the
group has more ideas regarding the impact
K could have on scholarly research. For
instance, with some modifications, the
algorithm could reach beyond books and
be repurposed for other heritage objects.
According to Rushmeier, in exploring
the material properties of medieval
manuscripts with computer science, we
have only “scratched the surface.”
ABOUT THE AUTHOR
AMANDA BUCKINGHAM
A junior in Berkeley College, Amanda Buckingham is double majoring in
molecular biology and English. She studies CRISPR/Cas9 at the Yale
Center for Molecular Discovery and oversees stockholdings in the healthcare
sector for Smart Woman Securities’ Investment Board. She also manages
subscriptions for this magazine.
THE AUTHOR WOULD LIKE TO THANK Dr. Holly Rushmeier and Dr.
Ying Yang for their enthusiastic and lucid discussion of a fascinating,
interdisciplinary topic!
FURTHER READING
Yang, Ying, Ruggero Pintus, Enrico Gobbetti, and Holly Rushmeier.
“Automated Color Clustering for Medieval Manuscript Analysis.”
24 November 2015

environment
FEATURE
ICELAND’S VOLCANIC ACTIVITY
TO INCREASE WITH CLIMATE CHANGE
BY ELLIE HANDLER
PHOTO BY STEPHEN LE BRETON
The Vatnajökull ice cap is the largest glacier in Iceland,
covering eight percent of the country’s landmass.
In 2010, there was a buzzworthy eruption of the Icelandic
volcano, Eyjafjallajökull. Its ash cloud caused a huge disruption
to air traffic, cancelling thousands of European flights for five
days.
In Iceland, the legacies of volcanoes and glaciers are
largely intertwined. Telling a story about one depends on an
understanding of the other. This was certainly true for the 2010
volcanic eruption, and it has great implications for the future. As
the planet suffers increasing climate change, a rise in Iceland’s
magma levels could spike volcanic activity.
How do volcanoes and glaciers — a dichotomy of hot and cold
— affect one another? Scientists can look at levels of magma,
or melted rock inside the earth, to predict whether a volcano
will erupt. Magma levels are a key indicator of underground
unrest. Although rocks melt at different temperatures based on
composition, rocks held at low pressures tend to melt at lower
temperatures. The massive weight of glaciers causes significant
pressure on the earth below, compressing the crust and pushing
down through the mantle, where magma forms. As glaciers melt
and their volumes decrease, they exert less downward pressure,
which allows the rock beneath to melt into magma more quickly.
Then, the increase in magma beneath the earth’s surface can have
a substantial impact on the volcanic activity above ground.
Several studies over the past decade have examined the rate of
magma formation as a result of deglaciation in Iceland. Located
along an Atlantic Ocean fault line and above a hot spot, Iceland
is a powerful source of volcanic activity. Glaciers are prominent
above its volcanic areas, posing a complicated geological problem
as deglaciation pushes forward with climate change. Warming
contributes to a faster melting of glaciers, a subsequent faster
melting of rock into magma, and the potential for more volcanic
eruptions. Climate change could spark such a series of events.
The first suggestion at a connection between deglaciation and
increased magma production in Iceland came in 1991. Two
scientists, Hardarson and Fitton, looked into deglaciation of the
late Pleistocene age and found a distinct correlation between ice
melting and magma formation. Another of the earlier studies,
published in 2008, focused on the Vatnajökull ice cap, the
largest ice cap in Iceland. The researchers found that the glacier’s
thinning and retreating caused roughly 0.014 cubic kilometers
of magma to form each year. As a result of this magma growth,
the researchers predicted an increase in volcanic activity under
the ice cap.
More recently, a 2013 study examined a larger area of the
mantle under Iceland’s crust. Led by Peter Schmidt of Uppsala
University in Sweden, the team used updated mathematical
models to understand how the mantle melts. The scientists
concluded that 0.2 cubic kilometers of magma melts each year
under Iceland’s crust — a figure that correlates to 0.045 cubic
kilometers of magma melting per year under the Vatnajökull
ice cap. These studies are not necessarily inconsistent. Rather,
the increase between their figures is due to an improved
understanding of how the mantle melts into magma.
According to Yale geology and geophysics professor Jeffrey
Park, the explosivity of a volcano is determined by the magma’s
chemical composition. Rocks with volatile compounds, such as
water, carbon dioxide, sulfur, and silica, melt and form magma
containing pockets of gas or liquid that cause explosive eruptions
with large ash clouds. Eyjafjallajökull’s eruption was dramatically
explosive because it included silica-rich magma that had been
sitting in the crust of the earth for hundreds of years. In contrast,
this year’s eruption of Bardarbunga, a volcano underneath the
Vatnajökull ice cap, has emitted about eight times as much
magma as Eyjafjallajökull, but without a massive ash cloud or an
explosive eruption due to variations in magma composition.
Many unanswered questions remain about how Iceland’s
volcanoes react to deglaciation. “We don’t know how much of the
magma being generated is reaching the surface,” Schmidt said,
referencing the difficulty of estimating the probability of future
eruptions. Moreover, the distribution of magma underneath
Iceland is still unclear to researchers, who know how much
magma is produced, but not where it goes. How long magma
remains magma is also uncertain, as it will eventually solidify to
become part of the earth’s crust. Finally, researchers are unable
to thoroughly predict the composition of magma in a chamber,
making it challenging for them to know which types of eruptions
to anticipate.
Deglaciation in Iceland is causing the melting of more magma
and increasing the likelihood of volcanic activity in Iceland. But
researchers are not sure exactly how the increase in magma
volume will affect the frequency or power of eruptions. For
now, scientists remain uncertain whether an eruption with the
magnitude of Eyjafjallajökull’s in 2010 will happen again in a few
years or a few decades. What they do know is that another major
eruption is surely on its way.
November 2015
25

An estimated 0.7 percent of power plants today use nuclear
power to sustain a whopping 5.7 percent of the world’s energy
and 13 percent of the world’s electricity. Despite the clear importance
of nuclear power plants, they do not operate without
risk. Indeed, on-site explosions can release radiation equivalent
to that of multiple atomic bombs — radiation that persists,
seemingly without end, for thousands of years.
Though nuclear plant explosions are uncommon, several
have occurred in recent decades. One of the most infamous
examples occurred in 1986, when a nuclear reactor exploded
in Chernobyl, spewing massive amounts of radioactive material
into the atmosphere. Shockingly, scientists estimate that
this explosion alone released a hundred times more radiation
than the atomic bombs dropped on Hiroshima and Nagasaki.
The explosion at Chernobyl is well known, but what is less
clear is exactly what makes radioactive matter so deadly. Radioactive
materials often come in the form of high-energy
photons, or tiny packets of energy, that can permeate through
matter impermeable to ordinary, less-energetic photons. Human
health is at stake when radioactive elements work their
way into cells. This dangerous material can cause deaths, deformities,
and cancers when it encounters bodily tissue, depending
on the type and amount of radiation released. The infamous
Chernobyl disaster, the deadliest unintentional release
of radioactive matter in history, accounts for just shy of one
IMAGE COURTESY OF REBECCA ABERGEL
Rebecca Abergel stands with her team of researchers.
million deaths to date.
Until recently, scientists have known little to nothing about
how cells take in high-energy radioactive materials. This past
July, a team led by Rebecca Abergel of the Lawrence Berkeley
National Laboratory in collaboration with Roland Strong
of the Fred Hutchinson Cancer Research Center discerned a
pathway for the cellular uptake of radioactive matter. With
this new insight, the researchers hope to bring a drug counteracting
radioactive health effects to the clinic. A solution that
assuages the bodily damage caused by high-energy photons
would aid those suffering from the aftermath of disasters like
Chernobyl. While it may be impossible to eliminate all radioactive
catastrophes, the goal for Abergel, Strong, and their colleagues
is to find better ways to respond to future disasters.
During nuclear reactions, many heavy elements autonomously
emit radiation. The fact that these heavy metals spontaneously
spew out photons of energy makes them highly
dangerous and intractable. The pathway identified by Abergel’s
team concerns heavy metals such as americium and plutonium,
classified in a group called actinides. The researchers
made a cluster of new discoveries, but most importantly, they
determined that a known antibacterial protein called siderocalin
is capable of carrying actinides into the cell.
Abergel and her group have a history of achievement in this
area. Before their discoveries about siderocalin, they had already
developed a molecule to isolate and subsequently remove
actinides from the body, which currently awaits approval
from the FDA. In a pill, the molecule may help to remove
some actinides from the body. However, its efficacy is limited
because it works mostly for metals that are still circulating,
not for metals that have already been imported into the intracellular
space. There was a gap in scientific knowledge of how
radioactive elements enter the inside of a cell, and Abergel was
determined to fill it. The limitation she noticed in her drug
helped motivate her group’s efforts to decipher a more mechanistic
understanding of how cells are contaminated with radioactivity.
Determining the precise role that siderocalin plays in the
cascade of events leading to actinide absorption was a challenging
task. The researchers combined experimental techniques
spanning different disciplines, from heavy-metal inor-
26 November 2015

ganic chemistry to structural biology. They hypothesized that
siderocalin might be a good protein to investigate because of
its known role in the sequestration of iron, a lighter metal,
in the cell. However, they were uncertain whether siderocalin
could carry heavier metals such as actinides — no structures
of protein-heavy metal ion complexes have ever been cited in
scientific literature.
But the team hypothesized correctly, and found that siderocalin
can indeed transport metals heavier than iron. First,
Abergel’s group created crystals that each contained many
identical snapshots of siderocalin in the action of carrying an
actinide ion. Next, the team took its crystals to the Advanced
Light Source, a synchrotron X-ray source owned by the Department
of Energy and located at Berkeley Lab. There, the
researchers fired X-rays — high-energy photons — at their
crystals.
Because the wavelength of an X-ray is approximately the distance
between the atoms in these crystals, X-rays were unable
to pass through untouched. Instead, they were bent, or diffracted,
by the varying electron densities at different points in
the crystal. The extent to which these rays were bent created
what is known as a diffraction pattern that contained an abundance
of exploitable information about the crystal’s structure.
With further mathematical analysis of their diffraction patterns,
Abergel and her team inferred the original regions of
high and low electron density in their crystals. From this data,
the group constructed atomic models that specify the original
structures of siderocalin attached to different heavy metal ion
complexes. These atomic models help to explain the mechanism
for cellular uptake of actinides. In general, the structures
suggest that first, smaller molecules recognize actinides in the
cell and form complexes around the heavy metal ions. Then,
siderocalin recognizes these complexes and shuttles them further
into the cell to be absorbed.
The group’s discoveries did not stop there. While searching
for a mechanism for the cellular uptake of heavy metals, Abergel
and her team also found a way to readily identify the
presence of these metals in vitro, or in a test tube rather than
a living cell. It was truly a testament to science and serendipity.
The researchers discovered that the crystals they originally
prepared actually luminesced under exposure to ultraviolet
ART BY HANNAH KAZIS-TAYLOR
light. Through a series of follow-up tests, the team demonstrated
that siderocalin can also act as a synergistic antenna
that causes heavy metals to glow much more brightly than they
would if exposed to ultraviolet light in their bare form. This
discovery highlights potential applications for siderocalin in
the field of bioimaging, which relies on luminescent signals in
a variety of scenarios.
With new knowledge about siderocalin and actinides, Abergel’s
team hopes to improve the lives of many who have been
exposed to radioactive materials.
November 2015
27

FEATURE
robotics
Robots
with
Electronic
By Caroline Ayinon
Art By Ashlyn Oakes
Skin
The race to develop viable, efficient robotic skin is on.
Such a technological triumph could make robots more
durable for use in a variety of settings, and could
even pave the way for improvements in human prosthetics.
Currently, an innovative and versatile material called graphene
appears to be the front-runner in this race. A research team at
the University of Exeter has developed a new way to produce
graphene that could allow for the creation of electronic skin.
Graphene is an incredibly versatile material that is just one
carbon atom thick — so thin that researchers consider it twodimensional.
An ultra-thin graphene sheet is transparent,
absorbing just 2.3 percent of the light that hits it. Graphene
is also an excellent conductor of electricity. Since electrons
are able to travel through it with virtually no interruption,
it conducts electricity up to 200 times faster than silicon, a
material it commonly substitutes. And while graphene can be
easily engineered into a soft powdery substance such as pencil
graphite, its flat honeycomb pattern also makes it the strongest
material in the world.
While scientists began to study the concept of graphene as
early as the 1940s, many then believed that the isolation of a
two-dimensional material was physically impossible. Graphene
did not come to the forefront of research initiatives until 2004
and 2005, when papers from the University of Manchester and
Columbia University published descriptions of its versatile
properties. Soon after, a team at Manchester isolated layers
of the material 10 carbon atoms thick from graphite using
a mundane product: tape. Later, the same team refined this
method to isolate a single layer using more advanced tools.
With the ability to synthesize graphene into layers, researchers
began to discover rich possibilities for the material. Graphene
layers stacked on top of each other and rolled to form carbon
nanotubes are starting to appear in tennis rackets, bicycles,
and 3D printed organs. When these same layers are wrapped
around each other, graphene can form spherical carbon
molecules called fullerenes, which are currently the focus of
While graphene can be
easily engineered into a
soft powdery substance
such as pencil graphite,
its flat honeycomb pattern
also makes it the strongest
material in the world.
many research studies because of their use in drug delivery.
Since graphene’s structure contains flexible carbon bonds, it
can bend and stretch in a multitude of ways without breaking,
opening up further possibilities for its use in devices such as
phone screens and plasma televisions.
Now, a group of University of Exeter researchers led by
28 November 2015

obotics
FEATURE
Monica Craciun has discovered a new technique for graphene
synthesis that could revolutionize the use of this material.
Recently published in Advanced Materials, the new method —
called resistive-heating cold-wall chemical vapor deposition —
is an improved version of the currently used regular chemical
vapor deposition technique, or CVD. Traditional CVD relies
on the use of a specific substrate to collect a deposit of gaseous
reactants. This process involves heating coils of copper inside
a quartz furnace to about 1,000 degrees Celsius for several
hours, which requires a lot of energy and produces a lot of
methane gas. CVD has been used and modified for several
years, but up to this point, the process has been too costly and
painstaking to be widely used.
The new resistive-heating cold-wall CVD is a simplified
version of the time-tested CVD method. Craciun and her team
were able to modify the process to selectively heat just the
copper foils, eliminating the need for hydrocarbons required
in the older version. This method shortens the entire reaction
and erases the dangerous output of methane gas.
Since resistive-heating cold-wall CVD hinges on a concept
that has already been used with much of the same equipment
to manufacture other materials, it could be employed
economically. Manufacturers entering the graphene industry
would not have to spend money on new facilities and would
instead be able to mass-produce the material with machinery
that is already available. Furthermore, Craciun’s technique is
a much simpler process and synthesizes graphene of the same
quality at a rate that is 100 times faster and 99 percent cheaper.
Using their improved graphene synthesis technique, Craciun
and her colleagues developed the world’s first flexible,
transparent touch sensor. Working with another Exeter team
led by Saverio Russo, they found that molecules of ferric
chloride inserted between two layers of graphene enable a
transparent conductor system that could replace silicon and
other materials in flexible electronics such as touch screens
and LCDs. In these devices, touch sensors provide the main
interface for detecting human input. When compared to the
touch sensors widely used today, the graphene-based sensors
developed by Craciun’s teams have exhibited some of the fastest
response times and most acute sensitivity to human touch.
Improvements in graphene synthesis could also enable
researchers to create flexible, sensitive skin that would
transform robotics technology. The machines that we associate
with the term “robot” most typically have rigid, metal shells.
While these hard-skinned robots have enormous capabilities
in a wide range of fields such as space exploration and warfare,
their inflexibility makes them susceptible to damage such as
breaks and scratches. To avoid such damage, researchers have
recently begun to develop robots made from softer materials
such as plastic and rubber, which allow robots greater
flexibility in avoiding obstacles and navigating through tight
spaces. However, these softer materials are fragile and have
also proven to be relatively inefficient in protecting robots
from damage.
This is where the graphene-based touch sensor skin would
come in. Similar to human skin, it would offer a great balance
between protection and flexibility and would allow the robots
a vast range of movement. Additionally, it could respond to
external stimuli from the environment and could guide the
robot’s responses just as neurons in our skin do. Specific
algorithms would govern the robot’s responses to various
physical stimuli, extending its perceptual capabilities. The
algorithms would interpret and analyze the information
received by touch sensor skin and would use it to guide the
robot’s resulting actions.
With soft, electronic skin, robots could prove more useful
in areas such as search-and-rescue missions, where hazardous
and unpredictable environments pose a threat to both humans
and currently available robots. Robots with tough artificial
skin could survive large jumps or falls, bend or stretch as
necessary to make it through difficult openings, and avoid
major harm in the process. For similar reasons, these next
generation robots could also see a potential application in the
exploration of the moon and space.
Another even more powerful application of Craciun’s
discovery is the potential use of her new method in research
pertaining to the development of artificial skin in human
prosthetics. Materials currently used in prosthetics have been
unable to replicate the hysteresis curve of human skin — the
way skin reacts to pressure forces. Graphene-based touch
sensor technology may just hold the answer.
An innovative concept, resistive-heating cold-wall CVD
has attracted a lot of attention from engineers and scientists
around the world. With its simplified production process, it
may just prove to be the future of many fields of technology
and engineering. What awaits is a world of extremely precise
touch screen electronics and robots with skin as sensitive and
intelligent as ours.
November 2015
29

FEATURE
computer science
COMPUTER ANALYSES PREDICT
ONSET OF PSYCHOSIS
BY KENDRICK MOSS UMSTATTD
Many view mathematics and language as two distinct areas of
study. But what if math could shed light on the significance of
the speech patterns of someone at risk of developing psychosis?
A recent computer algorithm developed by Guillermo Cecchi
of IBM and Cheryl Corcoran and Gillinder Bedi of Columbia
University demonstrates that mathematical speech analysis
can lead to some fascinating findings.
Schizophrenia, which afflicts approximately one percent of
Americans, is one such disease that can be better understood
with the use of speech analysis. The condition is characterized
by a number of symptoms, including psychosis — a feeling
of being detached from reality — and speech that deviates
from normal patterns. People with schizophrenia often have a
difficult time staying on one train of thought, instead jumping
from one topic to another as they speak.
Although psychologists have made great strides to better
understand the composition of a brain with schizophrenia,
there has been a comparative lack of information about the
behavior of those at risk of developing psychosis later in life.
Currently, the primary interviewing method for predicting
psychosis relies on human analysis of speech patterns. With
a 79 percent accuracy rate, this method is fairly reliable — but
what if its accuracy could be increased to 100 percent?
As the most objective and meticulous of analyzers, computers
could achieve this perfect record in predicting psychosis from
speech. Corcoran, who has a background in schizophrenia
prognosis, said that although a researcher speaking to a group
of teenagers cannot tell who will develop schizophrenia, a
computer can pick up subtle language differences among the
group. In a study of 34 people, computer analyses of speech
patterns in interviews perfectly predicted which five of the
patients would later develop psychosis.
To conduct this computer analysis of speech, researchers
first had to establish a paradigm of normal speech patterns.
They studied word relations from famous works of literature,
including Charles Darwin’s On the Origin of Species and Jane
Austen’s Pride and Prejudice. For example, the words “chair”
and “table” were classified as related because they often
appeared in close proximity in writing and speech, whereas
“chair” and “dragon” were not related because these words
almost never appeared together.
Using this understanding of word relations, a computer
could analyze the speech from patient interviews to examine
complexity and semantic coherence, or the relation of adjacent
words in a sentence. The computer analysis then created what
Cecchi describes as a syntactic tree of the patients’ speech
patterns. The more cohesive and complex the speech, the more
elaborate the tree — and the more likely that the patient would
continue to behave normally. However, choppy, tangential
speech — represented by a short tree with underdeveloped
branches — indicated that the patient had a relatively high
likelihood of later developing psychosis. This speech analysis,
coupled with examination of the patient’s behavior, could
provide researchers with a more holistic understanding of
psychosis.
The next step for these researchers is to validate the
results with a larger sample size. Once this is completed, the
possibilities for implementing the research are broad. The
study’s results not only shed light on the condition of those who
suffer from psychosis, but also provide a better understanding
of the general population’s mental state. “[Psychosis is] just
one end of the spectrum,” Cecchi said. “We all express these
conditions, and they form part of our mental life.”
With this knowledge, artificially intelligent robots could be
designed to more accurately represent the way people think
and act. The research could also be applied in medical care:
While search engines are optimized for individuals and social
media pages offer streams of personalized updates, there is not
yet an app that provides diagnoses for users based on whether
their speech is slurred. Beyond behavioral tracking, cell
phones could also be equipped with physiological-monitoring
capabilities to better track users’ heart rates or record their
brainwave activity.
This research could be meaningful in scientific efforts to
understand other elements of the human condition. The next
step is to determine what questions about speech patterns
need to be answered, and which speech variables can answer
these questions. Intonation or cadence, for example, may
be missing links in our understanding of a psychological
condition. Where will the results take us? If math continues to
be used as a key to unlocking the patterns behind behavior, the
possibilities seem endless.
ART BY ALEX ALLEN
30 November 2015

I
DEBUNK NG
SC ENCE
BY RAUL MONRAZ
Last spring, an M9.6 earthquake wreaked havoc in California. The
long overdue, gargantuan quake leveled the cities along the infamous San
Andreas Fault line. Los Angeles, San Francisco, and their surroundings
were plunged into chaos. Unleashing violent tremors from deep beneath
the earth, the disaster triggered fires, power outages, and the mother of
all tsunamis.
Rather than being petrified in fear, our Californian peers can assure
us that they witnessed this catastrophe over popcorn and soda from the
safe vantage points of darkened movie theaters, confident that Dwayne
“The Rock” Johnson would save the day. San Andreas, Hollywood’s
latest natural disaster blockbuster, played on the anxieties of many West
Coast denizens by offering a glimpse of what is to come when the next
anticipated mega-earthquake actually hits.
Not counting Johnson’s unlikely stunts, the film got most of the
generalities of emergency protocol right. As disasters strike throughout the
film, characters know to drop immediately to the ground and hide below
sturdy objects. Characters recognize the sea’s drawing in as a predictor of
an incoming tsunami. Early warning systems cry loud across the coast,
saving many lives by goading people up to higher ground. Fans watching
San Andreas get a rudimentary course in emergency management:
“What to do when Seismic Hazards, Inundations, and Tsunami hit you.”
Nevertheless, this film would probably not be a box office hit without
some well-done, albeit hugely exaggerated, CGI. The dramatic implications
of unrealistic events are enough to cause moviegoers to gawk in awe.
With the aid of movie magic, the film perpetuates three big scientific
inaccuracies: the magnitude of the earthquake and its consequences, the
size and very occurrence of the tsunami, and the existence of a high-tech
magnetic pulse model for predicting earthquakes.
In the movie, even the first earthquakes — between 7.0 and 8.0 on the
Richter scale — produce much more damage than they would in reality.
Additionally, seismic waves in the film violently shake and collapse the
majority of city buildings; with gross inaccuracy, an M7.1 quake obliterates
the Hoover Dam. In 2008, a panel of U.S. Geological Service experts
modeled the impact of a big earthquake in the southern California area.
The project predicted major structural damage, but mostly on buildings
that fail to comply with building codes or that have not been adapted to
withstand earthquakes. In all, few buildings would come to the point of
total collapse, and most would be within 15 miles of the San Andreas
Fault, rather than spread far and wide.
Still, viewers who have not experienced a major earthquake themselves
may take the destruction simulated in San Andreas at face value, since
real-world media outlets similarly dramatize disaster damage. In their
coverage, the buildings shown are typically those that have sustained
the most damage during earthquakes, rather than those that have been
left mostly unscathed. Even the most devastating earthquakes, such
as an M7.9 one that afflicted Nepal last April, did not cause a majority
of buildings to collapse. A survey by the Nepali Engineers Association
found that only 20 percent of buildings sustained major damages from
the quake. About 60 percent of the buildings struck down in the area
were masonry-built and lacked steel structures, construction methods
outlawed in California since 1933.
The film really starts to wander into fiction when Paul Giamatti’s
character, a purported geological expert, goes on national television to
announce the onset of a “swarm event,” a string of unfolding earthquakes
rippling from Nevada to San Francisco. According to his “magnetic
earthquake prediction model,” the geologist warns Americans that “The
Big One” will ultimately strike San Francisco with magnitude 9.6. Its force,
he says, will be such that “the earth will literally crack open.”
Earthquake swarms are real, several earthquakes may in fact occur
within a relatively short period of time. However, swarm event earthquakes
typically fall within a given magnitude and do not have a distinguishable,
main earthquake. While a swarm could account for the multiple quakes
in the movie, the San Andreas quakes have magnitudes far higher than
those typical of real-life swarm earthquakes. For comparison: a swarm of
101 earthquakes took place from July to November in Nevada last year,
with a maximum magnitude of 4.6 — far milder than the M9.6 quake
predicted in San Andreas.
When it comes to tsunamis, even a small one is extremely unlikely to
happen. The San Andreas Fault is located inland, far away from the coast.
An earthquake must occur in the ocean floor or at least close to the sea for
a tsunami to occur. Finally, the magnetic pulse predicting model is so far
— unfortunately — only science fiction. If such a model existed, it would
have been implemented already, as predicting these natural disasters
would surely save many lives.
While we can appreciate San Andreas’ wake up call for preparedness,
its science is implausible. The movie crosses into science fiction by
greatly exaggerating the destructive power of a natural phenomenon and
blatantly conjuring up impossible scenarios. Californians, you need not be
Hollywood superstars to weather The Big One — just educate yourselves
on earthquake safety and be ready.
IMAGE COURTESY OF NEW LINE CINEMA
Dwayne “The Rock” Johnson stars in the 2015 summer blockbuster
San Andreas. The movie was a dramatic take on what would
happen if a major earthquake struck the West Coast, complete with
November 2015
31

FEATURE
electronics
Sørensen’s and his team were after a substance that naturally
organizes into well-defined layers. They wanted something that
would not only sandwich thin films of electronic components, but
would also align these components in the same direction. Here,
they turned to soap.
This may seem like a surprising choice, since day-to-day experiof
electronics
BY NAAMAN MEHTA
Throw a potpourri of transistors into the bathtub, add some
soap, and out comes a fully formed nanocomputer. Science
fiction? Maybe not. Nanoscientists dream of coaxing
electronic components to self-assemble into complex systems.
In fact, researchers at the University of Copenhagen have taken a
major step towards making self-assembling electronics a reality.
In August, the researchers — many of whom were first-year
undergraduate students at the time of the work — reported that
they had successfully induced randomly oriented molecular
components to organize themselves into uniform sheets. At a time
when electronic components are so small that it is a formidable
challenge to position them accurately, self-assembly presents an
elegant solution. Soap was the key ingredient to their success,
forming thin films that sandwich the target molecules and precisely
guide their orientation.
“Imagine you have a billion nanocomputers but they are all
randomly oriented. You can’t harness the incredible computing
power, nor can you ‘plug in’ the keyboard, the mouse, or the screen,”
said Thomas Just Sørensen, leading investigator on the study and an
associate professor at the University of Copenhagen. “We need [the
nanocomputers] to be orientated in the right way to each other, and
that’s what our work seeks to accomplish.”
The promise of self-assembly
Nature provides inspiration for the flurry of work on selfassembly.
From the aggregation of phospholipid molecules
into cell membranes to the association of protein subunits into
nanomachines that churn out energy when we metabolize sugars,
nature creates elegant and intricate structures. These structures
form spontaneously, without outside intervention — the tendency
to self-assemble derives from the nature of the materials themselves.
Self-assembly holds great appeal given that electronic components
have become incredibly small. Currently, the transistors that make
up computer chips are positioned and wired together on circuit
boards using light, but this top-down approach is limited by the
light’s wavelength. With bottom-up nanoscience and the right
materials, the building blocks could do the hard work of assembly
themselves.
Besides, self-assembling materials are more resilient than their
traditional counterparts. If they can self-assemble once, it is
generally safe to assume that they can self-assemble again upon
suffering any damage. “If you break part of the material, there will
be some kind of self-healing effect,” Sørensen said.
According to Sørensen, display technology is one field where selfassembling
electronics promise a big splash. “All the technology in
our smartphone is remarkably robust except for the screen,” he said.
“There are no movable parts really. So you can hit it with a hammer,
and if the screen doesn’t break, probably nothing else will.”
Soap: The magic ingredient
32 November 2015

technology
FEATURE
ence suggests that mixing soap and circuitry is a bad idea. But the
molecules that make up soap are excellent at forming layers (think:
soap films). The water-loving ends of these molecules tend to stick
together, as do their water-fearing tails. These films, the researchers
hoped, would provide a regular template to guide the orientation of
all molecular components added.
Not just any type of soap will work. As the team found, soap
molecules found in common items such as shampoo and toothpaste
lack the required rigidity to hold the molecular components tightly
in place. Eventually, the group settled on a more grease-loving soap,
benzalkonium chloride, which also happens to be an anti-fungal
drug.
The team produced impeccably organized structures simply by
mixing these soap particles with a range of dye molecules. The soap
molecules quickly sought out other soap molecules and organized
into thin films that effectively glued together layers of dye molecules.
Even more impressive: the dye molecules oriented themselves in a
common direction, lying flat on their sides just as a layer of bricks
would pave a walkway.
Still, Sørensen estimates that self-assembling electronics may be
more than ten years away. In this proof-of-concept experiment,
the researchers did not work with actual electronic components.
Instead, they substituted similarly sized dye molecules. The
nanomaterials they produced do provide insight into how soap
organizes other molecular components. These materials may have
interesting conducting properties in their own right — but they are
not functioning electronic parts.
Even so, finding a material that can interact with other molecules
to produce these elegant sheets is a leap forward, Sørensen said.
Better yet, the scientists have already replicated their results.
Working with a range of dyes with many different shapes, the team
has observed self-assembly in 16 different nanomaterials. The
Copenhagen scientists, among other researchers, are now chasing
the next big break: translating these results to make functioning
electronic parts.
A different philosophy to science education
The Copenhagen team’s work represents a breakthrough in
science education as much as it does a breakthrough in science.
This research grew out of coursework completed by first-year
undergraduates as part of a laboratory class. Instead of conducting
run-of-the-mill experiments, these freshmen enrolled in the
university’s nanoscience program and had the opportunity to
dedicate themselves to a modern engineering problem.
For Ida Boye, who took part in the fourth year of this research
and who will be graduating this year, it was thrilling to realize that
no one yet knew the answer to the questions that the team was
tackling. “You have to think for yourself and try to come up with
ideas, because there is no textbook telling you what is right and
wrong,” Boye said.
Aske Gejl, one of the second batch of students now completing
his master’s degree in nanoscience, credited this experience for his
continued passion for research and inquiry. “The project still stands
as one of the most important during my time at the university,
as this was the first time I was trusted and enabled to aid in the
progress of real scientific work. This only fueled my desire to strive
for an academic career,” Gejl said.
Getting first-year students involved in research, pushing them
to confront important questions, and having them see their work
published in journals was a major achievement for the university
staff, Sørensen said.
“The university is not just a teaching institute but also a research
institute, and it’s important that [students] get to see this other side
of the university,” he said.
Towards functional electronics
IMAGE COURTESY OF JES ANDERSEN/UNIVERSITY OF COPENHAGEN
Sørensen is already looking ahead. As the classroom experiment
moves into its sixth iteration, he hopes that the incoming batch of
students will be able to build upon the existing work and produce
functional self-assembling electronics.
Research teams elsewhere are hard at work trying to produce
these layered devices by self-assembly. These groups typically work
with larger compounds known as polymers instead of the smaller
soap molecules that have worked so well for the Copenhagen teams.
Sørensen explained that it might be easier to plug electrodes into
materials made using long polymer strands, which take the form of
boiled angel hair pasta: Each strand serves as a conducting wire, and
it suffices to use an alligator clip that contacts the material at any
two points. Soap films, on the other hand, require contacts small
enough to pinch each individual film layer — just nanometers thick
— and engineers have not yet developed electrodes that small.
Sørensen’s class, however, will continue to work with soap. He
believes that there is value in pursuing this different path, especially
for the first-year students who can afford to take bigger risks because
they have less at stake.
One way or another, Sørensen said, self-assembly will deliver.
“One day, we’ll be able to spread a thin layer of solar cells on the
window and start generating solar power,” he said.
Self-assembling computers may still be a nanoscientist’s fantasy for
now, Sørensen conceded. But as these remarkable films effortlessly
organize tiny components with a dexterity that has eluded man’s
best efforts, he is content to look on in wonder, marveling at how
soap and self-assembly could shape the future of our most advanced
electronics.
November 2015
33

FEATURE
engineering
WHO LIVES ON A DRY SURFACE
UNDER THE SEA?
BY AVIVA ABUSCH
April showers bring May flowers — and a host of other
problems. After donning what is marketed as a water
resistant rain jacket and wielding an umbrella to battle
the elements, there is nothing quite as disheartening as
feeling rain soak into a dry layer of clothing, or knowing
your thin backpack containing several textbooks and a
computer is being slowly saturated. What if rain gear
was scientifically incapable of getting wet, and was
actually able to repel water? Researchers at Northwestern
University are exploring this question as they work to
develop a material that stays dry underwater.
The research team, led by Northwestern mechanical
engineering professor Neelesh Patankar, began by looking
for properties that would allow a surface to be immersed
in water but emerge completely dry. Drawing inspiration
from water bugs, whose fine leg hairs repel water by
retaining gas pockets, the scientists began constructing
a material that keeps water away using microscopic or
nanoscopic ridges. The goal of their research was to
harness this fantastic feat of natural engineering.
First, they had to find the critical roughness scale for
gas trapping in a man-made material — the correct width
and spacing for ridges on a textured surface such that
they could trap gaseous air and water vapor in between.
This design would force water to cling to the peaks,
rather than touching the material itself.
Of course nothing in science is ever quite so simple,
as the team found in attempting to engineer a perfect
texture. There was little to no research available on how
to create an effective surface roughness to deflect water.
And for the material to stay dry, the gas contained in
the valleys of the ridges would have to remain trapped
indefinitely. As pioneers in their field, Patankar and his
fellow researchers went through a series of experiments
to find the optimal distance between ridges.
Initially, their sample materials containing microscopic
ridges lost their ability to deflect water after only a few
days. By putting several samples through aging and
degassing trials, they discovered that their ideal material
needed even smaller ridges — on the nanoscopic scale.
In fact, the material that successfully withstood the
degassing trials had ridges roughly 10 times smaller than
the width of a strand of spider silk.
The discovery that they needed to work on the nanoscale
was a turning point for the researchers. According to
Patankar, they noticed that once the valleys dipped below
one micron in width, the pockets of water vapor created
due to underwater evaporation and effervescence finally
withstood the test of time. The trapped gas continued to
successfully deflect water, even after the scientists made
multiple attempts to dislodge it.
Beyond a future of water-repellant backpacks and
umbrellas, the material created by Patankar’s team has
the potential to change and economize major world
industries. Because water cannot stick to this surface,
it could revolutionize plumbing, especially in big cities.
In pipes lined with the material, the drag that currently
occurs due to the interaction between the interior of
the pipe and the fluids within it would be eliminated,
meaning water and liquid waste could be transported
much faster. Additionally, the material could be used to
make more weatherproof roof tiles and house sidings.
This would greatly reduce the frequency with which
homeowners have to undergo costly renovations for
basic maintenance, and could have a lasting impact on
both architecture and realty.
These tiny ridges offer tremendous possibilities. Their
applications are limited only by engineers’ imaginations.
Understanding water deflection could improve footwear,
kitchen appliances, outdoors supplies, aquatic sports
equipment, underwater research capabilities, and more.
Researchers can use ever-dry surfaces to achieve big
projects — provided that they first remember to think
small.
IMAGE COURTESY OF DARTHMOUTH COLLEGE
Patankar’s research ideas were derived from the water
deflection capabilities of water bug legs. These bugs are one
example of how nature can inspire next generation technology.
34 November 2015

Science or
Science Fiction?
BY AMANDA MEI
Telepathy and Mind Control
Imagine stepping into a room and catching the eye of
someone inside. You exchange no words, you give no
smile. But somehow, you both know you’re saying “hi.”
It’s like telepathy — your brains are in sync.
What if you were in India, and the other person in
France? Would brain-to-brain communication still be
possible?
According to research done by scientists in
Barcelona, Boston, and Strasbourg, the answer is yes.
The study marked the first time conscious thoughts
were transmitted directly between individuals. By
recording the brain signals of one person in India with a
computer system, converting them into electrical brain
stimulations, and relaying them to recipients in France,
the research team developed a noninvasive method of
brain-to-brain communication. The transmissions were
simple greetings: “hola” in Spanish and “ciao” in Italian.
“This represented the first time a human knew what
another was thinking in such a direct way,” said Giulio
Ruffini, CEO of Starlab Barcelona and author of this
study.
To achieve brain-to-brain communication, the team relied
on a process called synaptic transmission. Chemical
signals are transmitted between neurons through spaces
called synapses, generating electric impulses in the receiving
neurons. These impulses drive brain function for
activities including motor skills and sensory perception.
In the experiment, the non-invasive technologies electroencephalography
(EEG) and transcranial magnetic
stimulation (TMS) were used as interfaces with neuronal
synaptic signaling. EEG works with the sender of a message:
the technology uses a helmet-like device with electrodes
to record electrical activity from firing neurons
in a participant’s brain. Then, TMS takes this communication
to the recipient: the technology electrically stimulates
parts of the recipient’s brain to produce impulses
that can be perceived.
On the sending side, otherwise known as the brain
computer interface, researchers encoded the words on
a computer in binary code. The computer cued one
subject in Thiruvananthapuram, India to think about
moving either his hands for transmission of one or his
feet for zero. Then, the subject’s conscious thoughts were
recorded by EEG, decoded by a computer as a one or a
zero, and emailed to researchers in Strasbourg, France.
At the recipient computer brain interface, the EEG
PHOTO BY AYDIN AKYOL
signals received by email were converted for real time use
in TMS. This stimulation was then delivered to at least
three subjects, all healthy and between the ages of 28 and
50. TMS technology applied pulses to a recipient’s right
occipital cortex, which process visual information. Then,
with her vision darkened by a blindfold, the recipient was
able to perceive flashes of light called phosphenes in her
peripheral vision. For the binary signal one, TMS induced
phosphenes, whereas for the binary signal zero, TMS was
manipulated so that there were no visual signals. Finally,
the recipients and the research team could decode the
binary signals back into the original words.
Some previous studies have also used electrical
impulses in brain-to-brain contact, and researchers
have demonstrated human-to-rat and rat-to-rat brain
communication. In 2013, researchers at the University of
Washington induced human-to-human brain interfacing
for the first time. One man playing a video game imagined
pushing a button, causing another man in a different
room to subconsciously press the button. The results
from this experiment suggest new research directions for
noninvasive brain-to-brain communication, including
the transmission of emotions and feelings. “As we see it,
brain-to-brain interfaces are full of possibilities…. Most
of the world-changing tech innovations in mankind were
innovations of communication,” said Andrea Stocco, one
of the authors of the University of Washington paper.
Still, scientists who conduct brain-to-brain research
warn the public not to interpret brain-to-brain communication
as either telepathy or mind control. Telepathy
implies the exchange of information without any of our
sensory channels or physical interactions — we usually
imagine people sending thoughts to each other through
thin air. Scientists talk instead of hyperinteraction, or the
transmission of information from one brain to another
using non-invasive but still physical mechanisms.
As for mind control, Ruffini said he has no idea how
we could begin to achieve it. “There is no magic in our
work. It is based on hard-core science and technology
and mainly on Maxwell’s equations,” he said.
Despite what science fiction says, you cannot influence
the minds of other people or exchange thoughts with
them without both your senses and technology. People
might be 5,000 miles away or only a few steps across
the room, but unless they agree to wear helmets and
blindfolds, “hi” (or “hola” or “ciao”) is just a fantasy.
November 2015 35

UNDERGRADUATE PROFILE
GREG MEYER (MC ‘16)
CLIMBING MOUNTAINS, CONQUERING PHYSICS
BY GLORIA DEL ROSARIO CASTEÑEDA
Growing up surrounded by the beautiful landscapes of Vermont,
Greg Meyer (MC ’16) had a passion for motion. He remembers
how, as a child, he would play with sand for hours, watching it
change shape in his fingers and developing a basic intuition for
how things work. High school brought outdoor sports loaded
with terrifying thrills: kayak racing, 40-foot dives, and mountain
biking with his friends. “A basic understanding for a lot of
scientific things can come from just experiencing them and just
playing with them,” Meyer said. His early passion for hands-on
encounters would propel him into physics research at Yale, CERN,
and the National Institute of Standards and Technology.
When he started at Yale, Meyer’s dedication to FOOT took
root easily. He participated as a freshman and would continue to
be involved throughout his four years. At first, he took courses
spanning a smorgasbord of scientific disciplines — engineering,
neuroscience, and physics. Meyer soon settled on physics: It was
the most fun, an extension of his childhood curiosity about how
things work.
During his first two summers as an undergraduate, Meyer
conducted research in high-energy particle physics at CERN,
in Meyrin, Switzerland. While working at the laboratory, Meyer
lived in a small French town called St. Genis-Pouilly at the base
of the Jura Mountains. Living in France, it turned out, was not
only more affordable than Switzerland, but also presented some
interesting options for hiking.
While at CERN, Meyer conducted his thesis research on
supersymmetry — a system of mathematical predictions used to
anticipate and fix problems that arise with the Standard Model.
The Standard Model represents our current understanding of how
physical matter is made. Supersymmetry suggests that particles
already known in the Standard Model have partner particles. The
properties of these partner particles lead to cancellations that
could fix problems with the Standard Model, such as the question
of why the Higgs boson has the mass that it does.
In his thesis research, Meyer was searching for the stop quark,
the partner of the top quark in the Standard Model. To investigate
the stop quark’s existence, researchers examine the products
of decay events — processes in which unstable particles are
converted into energy or smaller masses. They look for events that
could be attributed to the quark. Still, many more trials are needed
to see sufficient statistical evidence that the stop quark exists. And
if it does, it would be rare.
Although Meyer no longer works with the supersymmetry
researchers at CERN, their project is ongoing: Another trial at a
higher energy is currently underway in search of better evidence
IMAGE COURTESY OF GREG MEYER
During a trip to Volcanoes National Park in Hawaii, Meyer hiked
to a volcano crater.
for the stop quark and for supersymmetry. Meyer’s thesis predicts
that if support for supersymmetry is not found during this higherenergy
run, the evidence may actually contradict the theory
behind supersymmetry. Thus far, supersymmetry has been elusive
even to the most dedicated physicists, and all evidence in support
of the theory has been indirect.
This past summer, Meyer sought a more hands-on project to
continue his work in physics. At the National Institute of Standards
and Technology (NIST) in Colorado, his research concerned
atomic clocks, which use electromagnetic radiation from atomic
transitions to keep track of time. Meyer created a computerprogrammed
device to account for the effects of magnetic fields
on the clocks at NIST. This research reprised a familiar theme —
his determination to put his talents towards better understanding
and experiencing the world.
Meyer continues to expand his knowledge of physics at Yale. As
a junior, he joined the Drop Team, which conducts microgravity
research. As he considers the future, he weighs his many areas
of interest, and looks forward to attending graduate school in
physics.
Of course, Meyer also makes time for outdoor activities —
Ultimate Frisbee, mountain biking, FOOT, and slacklining. “I love
doing physics and thinking, but sometimes it’s just nice to let your
cerebellum take over,” he said.
He did have one more thing to add, summing up his lively
nature: “Shout-out to my FOOTies!”
36 November 2015

ALUMNI PROFILE
MICHELE SWANSON (YC ‘82)
MICROBIOLOGIST AND MENTOR
BY PATRICK DEMKOWICZ
As a young woman, Michele Swanson ’82 did not anticipate
attending an Ivy League college. “I was one of six kids growing
up in Ohio. My dad was the first in his family to go to college,”
she said. Now, Swanson is a professor of microbiology at the
University of Michigan Medical School and a leader in the
American Society for Microbiology.
Swanson credits her success to the mentors who saw her
potential as a young adult. Following their examples, she now
mentors and advocates for young scientists herself. She believes
in the importance of public education on topics in science, and
even co-hosts a podcast to spread knowledge of microbiology.
Swanson’s journey to New Haven began when she met the
Yale field hockey coach at a summer camp in Michigan. Soon,
she was playing varsity field hockey and softball at Yale. She
also held a campus job and served as a freshman counselor for
Davenport College. Her senior year, she took an inspirational
class in developmental biology. “Professor John Trinkaus taught
with such passion that I really got interested in thinking like an
experimentalist,” Swanson said. Although it was too late for her
to get involved in research on campus, she secured a job as a lab
technician at Rockefeller University upon graduation.
Swanson reflects warmly on her early years in the laboratory.
At the time, she was content to assist graduate students, but
realized many of their exciting scientific discussions were
beyond her reach. She remembers the day when she asked her
laboratory head, Samuel C. Silverstein, for a recommendation
letter to apply for master’s degree programs, only to have her
initial request denied. “Instead, he sat me down and said, ‘I want
you to apply for PhD programs. I want you to think big and get
the best training you can at each stage of your career,’” she said.
Shortly thereafter, Swanson began graduate school at Columbia
University before moving with her husband, also a graduate
student, to Harvard. There, she would earn a PhD in genetics
with Fred Winston while also starting a family.
In 1986, Harvard was a difficult place to be a mother and
scientist. Swanson recalled the social pressure she faced as she
tried to excel at the lab bench while raising two children: “People
have a tendency to measure how deeply you are committed to
your research by the number of hours you spend at the lab. Any
working parent knows we have to care twice as much about our
careers to put in the same number of hours.”
In spite of the obstacles she faced as a mother, Swanson
persisted, with encouragement from her thesis advisor and other
faculty. After taking a year off to spend time with her children,
Swanson completed her postdoctoral training and was recruited
to the faculty at the University of Michigan, which jointly hired
her husband. There, she began a research program on how
Legionella pneumophila, the bacterium that causes Legionnaire’s
disease, thrives in immune cells. Her lab continues to make
significant contributions to our understanding of microbial
infections and immunity.
Remembering her own mentors, Swanson works to support
other young scientists. To this end, she has served in many
leadership positions at the University of Michigan. She is
currently the director of the Office of Postdoctoral Studies. She
has also been a member of the President’s Advisory Commission
on Women’s Issues, which develops policies, practices, and
procedures to enhance gender and racial equity. “I want to make
sure that other talented people, and women in particular, have
the same opportunities I had,” Swanson said.
Apart from her work at the University of Michigan, Swanson
is involved in the American Society for Microbiology, which
publishes journals, hosts professional events, and guides public
outreach efforts to advance the microbial sciences. She was
recently appointed as chair of the Board of Governors of the
American Academy for Microbiology. She also co-hosts a podcast
entitled This Week in Microbiology. The podcast has aired since
2011, garnering 1.2 million downloads over the course of 111
episodes. Swanson sees this podcast as an important effort to
educate the public on how microbes influence our lives.
Swanson believes that her experience at Yale reinforced in her
the values she lives by today, especially her desire to give back.
“I really believe the culture
at Yale strives to instill
that spirit in the community,
that we’re privileged to
be there but also have an
obligation to step up and
take leadership roles and
give back,” she said. Swanson
models these values
through her mentorship,
leadership, and commitment
to public outreach.
Her path to Yale and academia
shows that the difference
between chance
and fate is often decided by
one’s own passion and persistence.
November 2015
IMAGE COURTESY OF MICHELE SWANSON
Swanson is a professor at the University
of Michigan Medical School.
37

q a
&
BY ISABEL WOLFE
The satisfying crunch that accompanies
the first bite into a crisp apple is a quintessential
fall experience. Although we may
not realize it, this crunch affects the delicious
flavor we perceive.
Do we eat with our ears? Perhaps. Recent
research from Oxford University explores
how sounds impact our perception and enjoyment
of flavor.
Scientists have recognized that flavor is
a multi-sensory experience in which taste,
appearance, scent, texture, and sound are
all important ingredients. Indeed, Yale epidemiology
and psychology professor Lawrence
Marks acknowledges that it is difficult
to separate the components influencing flavor.
“The different [sensory] systems are always
integrating information,” Marks said.
Sounds perceived by the ear are converted
to electrical signals and are processed in the
Do you eat with your ears?
IMAGE COURTESY OF FREESTOCKPHOTOS
Experience the satisfying crunch of a
fall apple. Research shows that sound may
influence taste.
auditory cortex of the brain. However, scientists
are unsure exactly how the brain associates
these sensory signals with flavor.
In recent research, Oxford psychology
professor Charles Spence investigated this
phenomenon. Study participants ate and
described the taste of uniformly-flavored
chips while listening to crunching sounds.
Surprisingly, 75 percent thought the chips
tasted differently depending on which
sounds were played. When the volume of
crunching sounds increased, participants
rated potato chips as crispier and fresher.
Sounds produced by “quiet” foods and
drinks can also affect the perception of flavor
— participants reported that soda tasted
better when the volume and frequency
of bubbles was increased to produce a more
rapid fizzing sound.
So, the next time your mother tells you
to chew more softly, tell her the apple tastes
better when you make noise!
BY SUZANNE XU
Organisms have evolved to possess a
wide range of useful abilities: flight, poison
production, and even light emission.
Although humans never evolved the necessary
mechanisms to glow themselves,
some bioluminescent species can in fact
emit their own light. The trick? A specific
type of chemical reaction, which happens
to have many practical applications.
The basic mechanism for bioluminescence
is the same for most glowing species.
An enzyme, generically called luciferase,
interacts with luciferin, a molecule
that organisms may ingest or produce
themselves. This interaction yields two
products: a substance called oxyluciferin
and a photon of light, which can be observed
as glow.
Not all creatures stop there. Crystal jellies,
for example, emit photons of blue
light that are absorbed by their own green
How do some organisms glow in the dark?
fluorescent proteins and are emitted back
at a lower wavelength. This re-emission of
light produces a secondary type of glow
called biofluorescence.
IMAGE COURTESY OF WIKIMEDIA COMMONS
The fungi Panellus stipticus is an example
of a bioluminescent species.
To glow in the dark may seem impressive
in itself, but bioluminescence has
many practical uses as well. Approximately
80 percent of bioluminescent species
live in the deep sea, where they may glow
to attract prey or to distract predators.
Above water, species can use light to entice
mates or to make themselves seem larger
to predators. Bioluminescence also has applications
in the laboratory. For example,
professor Vincent Pieribone at the Yale
School of Medicine works on bioluminescent
methods to study action potentials in
neurons, which enable brain cells to communicate
with one another. He hopes that
these techniques will help scientists study
neural pathways in living subjects.
The next time you see a firefly or jellyfish
glowing in the dark, be sure to appreciate
the chemical processes that give them this
special talent.
38 November 2015

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