YSM Issue 90.1
You also want an ePaper? Increase the reach of your titles
YUMPU automatically turns print PDFs into web optimized ePapers that Google loves.
Yale Scientific<br />
Established in 1894<br />
THE NATION’S OLDEST COLLEGE SCIENCE PUBLICATION<br />
DECEMBER 2016 VOL. 90 NO. 1 | $6.99<br />
STICKING<br />
IT TO<br />
CANCER<br />
FIGHTING TUMORS<br />
WITH NANOPARTICLES
INDIUM AND<br />
GALLIUM<br />
COMPOUNDS<br />
AND METALS<br />
49<br />
In<br />
114.818<br />
Indium Corporation’s online store allows<br />
you to browse our selection of metals,<br />
compounds, and solder products.<br />
Our ecommerce site:<br />
• Is easy to use<br />
• Accepts credit cards<br />
• Offers a wide variety<br />
of products<br />
Compounds<br />
31<br />
Ga<br />
69.723<br />
EZ-Pour ®<br />
Gallium<br />
Trichloride<br />
Contact our technical engineers today:<br />
techsupport@indium.com<br />
Learn more:<br />
www.indium.com/YALE<br />
From One Engineer<br />
To Another<br />
®<br />
www.indium.com<br />
askus@indium.com<br />
ASIA • CHINA • EUROPE • USA<br />
©2016 Indium Corporation
Yale Scientific Magazine<br />
VOL. 90 ISSUE NO. 1<br />
CONTENTS<br />
DECEMBER 2016<br />
NEWS 6<br />
FEATURES 25<br />
ON THE COVER<br />
15<br />
STICKING IT<br />
TO CANCER<br />
Yale researchers demonstrate drug<br />
delivery efficacy via a bioadhesive<br />
class of nanoparticles designed for<br />
administering cancer treatment.<br />
12<br />
A ROCKY ROAD<br />
TO THE PAST<br />
Using new analytics to understand<br />
tiny mineral crystals, a Yale G&G team<br />
discovers evidence for the effect of<br />
volcanic activities on global climate.<br />
18<br />
CANINES ARE OVER<br />
OVERIMITATION<br />
A recent Yale study supports that<br />
overimitation is distinctly human,<br />
as dogs and dingoes are more<br />
inclined to evade irrelevant actions.<br />
20<br />
PERPLEXING FOSSILS<br />
& PECULIAR FORMS<br />
Researchers from Yale and other<br />
institutions unearth the origins of<br />
the Tully Monster, a Carboniferous<br />
creature with unusual morphology.<br />
“FEELING THE SURFACE TENSION”<br />
22<br />
EXPANDING QUANTUM<br />
COMPUTING<br />
Uniting quantum mechanics and<br />
computer science, Yale researchers<br />
make progress towards constructing<br />
more powerful quantum computers.<br />
More articles available online at www.yalescientific.org<br />
December 2016<br />
Yale Scientific Magazine<br />
3
q a<br />
&<br />
CO 2<br />
Past the point of no return?<br />
►BY MATTHEW KEGLEY<br />
Climate change has been ranked a top<br />
global threat, with indicators such as carbon<br />
dioxide (CO 2<br />
) levels illustrating its<br />
rapid progression. Each year, CO 2<br />
levels<br />
are lowest in September—but this year,<br />
even at their annual minimum, CO 2<br />
levels<br />
stayed above 400 parts per million<br />
(ppm). Scientists consider 400 ppm to<br />
be the “fail-safe” ceiling for CO 2<br />
levels.<br />
Beyond this concentration means that<br />
Earth has permanently surpassed 350<br />
ppm, the highest level needed to maintain<br />
climate stability. So when the Mauna<br />
Loa Observatory, a global monitoring facility<br />
in Hawaii, discovered that CO 2<br />
levels<br />
remained unusually high this year, the<br />
news was concerning for many experts.<br />
“We won’t be seeing a monthly value<br />
below 400 ppm this year—or ever again<br />
for the indefinite future,” said Ralph<br />
Keeling, director of the Scripps Institute<br />
for Oceanography, after he analyzed the<br />
IMAGE COURTESY OF WIKIPEDIA COMMONS<br />
►Smoke is emitted from factory smokestacks<br />
beside a highway.<br />
daily Mauna Loa recordings.<br />
With global CO 2<br />
continuing to rise,<br />
has our atmosphere been irreversibly<br />
altered? Joshua Galperin, research<br />
scholar and lecturer in law at Yale Law<br />
School and the Yale School of Forestry<br />
and Environmental Studies as well as<br />
the director of the Environmental Protection<br />
Clinic, believes we can address<br />
the problem if both policymakers and<br />
citizens make changes. “[Policymakers]<br />
need to be imaginative,” Galperin said.<br />
Specifically, he promoted the elimination<br />
of coal power as a starting point<br />
for energy reformation.<br />
Galperin further suggested that citizens<br />
use their skills in economies “built<br />
on carbon” to ensure integrity as they<br />
retract from carbon. He also emphasized<br />
the need for hope at the forefront<br />
of our actions to combat climate<br />
change.<br />
Three’s a Crowd—How can a baby have three parents?<br />
►BY MILANA BOCHKUR DRATVER<br />
Modern technology has allowed for the<br />
creation of “three-parent” babies by incorporating<br />
genetic material from three individuals<br />
in the creation of a single embryo.<br />
For parents whose children are at risk of<br />
inheriting a mitochondrial disorder, genetic<br />
material from a third person can<br />
help them conceive a healthy child. Mitochondria<br />
are maternally inherited organelles,<br />
so if a mother’s mitochondrial DNA<br />
is mutated, her children are at risk of developing<br />
defects that frequently result in<br />
infant death.<br />
Researchers first attempted to prevent<br />
mitochondrial diseases in the 1990s by<br />
injecting mitochondrial DNA from a donor<br />
into another woman’s egg, along with<br />
sperm from her partner. Some of these<br />
children developed genetic disorders, and<br />
the US Food and Drug Administration<br />
stopped the procedure.<br />
IMAGE COURTESY OF WIKIPEDIA COMMONS<br />
►Sperm cells surround and fertilize a human<br />
egg as seen under a light microscope.<br />
A recently approved method now used<br />
in the United Kingdom is pronuclear<br />
transfer: the mother’s and a donor’s egg<br />
are fertilized with the father’s sperm,<br />
both nuclei are removed from their respective<br />
eggs, and the mother’s nucleus<br />
is transferred to the donor’s egg. The embryo<br />
then possesses mitochondrial DNA<br />
from the donor, as well as nuclear DNA<br />
from its parents. In this way, the child<br />
has genes from three different parents.<br />
Recent successful three-parent-births<br />
give hope to parents who have lost children<br />
to mitochondrial disorders.<br />
“Mitochondrial diseases were incurable<br />
until now. The opportunity to use<br />
mitochondrial replacement as a form of<br />
cell therapy to provide a ‘cure’ should be<br />
embraced,” explained Pasquale Patrizio,<br />
Director of Yale Fertility Center & Fertility<br />
Preservation Program.
3<br />
The year began with the thrilling discovery of gravitational waves. We said that<br />
was just the beginning, and indeed what a year it has been for science and for us<br />
at the Yale Scientific. From breakthroughs in cancer therapy in To Immunity and<br />
Beyond (89.2) to advances in quantum computing in Welcome to the Quantum Age<br />
(89.3) to new approaches to art restoration in Decko Gecko (89.4), it has been an<br />
absolute joy sharing these fascinating scientific stories with you, our readers.<br />
On this issue’s cover, we are excited to feature research conducted at Yale that<br />
harnesses nanotechnology to target drugs to cancer cells with greater potency and<br />
fewer side effects (pg. 15). Not to be outdone, another Yale team has discovered a<br />
new drug candidate for lung cancer that acts through a novel mechanism (pg. 8).<br />
Meanwhile, across the Pacific Ocean, a group of researchers in Melbourne are exploring<br />
a novel approach to treating antibiotic-resistant bacteria (pg. 30).<br />
This year also marks the 150th anniversary of the Yale Peabody Museum (pg. 25).<br />
Museums like the Peabody inspire awe with their remarkable collections of fossils<br />
and minerals. Easier to forget is the fascinating research that goes on behind the<br />
scenes. The intriguing tale of the Tully Monster, a fantastic creature that has finally<br />
been assigned its proper place in the tree of life, pays tribute to those efforts (pg. 20).<br />
In many ways, the past holds insights for the present. In this issue, we dive into<br />
the changes in carbon dioxide levels that have taken place across geologic time as<br />
volcanic activity rose and fell. What we see is troubling, with surging carbon dioxide<br />
levels driving a majority of species to extinction (pg. 12). As greenhouse gas levels<br />
continue to rise, we evaluate where we stand today (pg. 4) and report on the quest<br />
for cleaner sources of energy (pg. 10).<br />
We worry about the future of climate change research as a new administration<br />
takes over in January. Still, we take heart in the progress that scientists and engineers<br />
around the world have already made, and we remain quietly optimistic that<br />
scientists will respond to the increased urgency for clean-energy solutions with a<br />
wave of innovation.<br />
At our magazine, it is also time for us to pass on the baton to a new masthead.<br />
We are struck by their boundless energy and their refreshing ideas, and we have full<br />
confidence that they will carry this publication to greater heights.<br />
Thank you for reading these pages. It has been our privilege and pleasure.<br />
Yale Scientific<br />
Established in 1894<br />
THE NATION’S OLDEST COLLEGE SCIENCE PUBLICATION<br />
DECEMBER 2016 VOL. 90 NO. 1 | $6.99<br />
STICKING<br />
IT TO<br />
CANCER<br />
FIGHTING TUMORS<br />
WITH NANOPARTICLES<br />
F R O M T H E E D I T O R<br />
A B O U T T H E A R T<br />
Lionel Jin<br />
Editor-in-Chief<br />
The cover, designed by arts editor Ashlyn Oakes, shows<br />
the artist’s interpretation of nanoparticles as they deliver<br />
drugs to cancerous endometrial cells. Endometrial cancer<br />
is resistant to many forms of chemotherapy and must<br />
be combated using powerful drugs which often have severe<br />
side-effects. In order to relieve some of those side<br />
effects and increase drug potency, Yale researchers have<br />
developed sticky nanoparticles that attach to the surface<br />
of tumor cells, delivering drugs in a targeted fashion to<br />
the tumor and promising safer, more effective treatments<br />
to a debilitating disease.<br />
Editor-in-Chief<br />
Managing Editors<br />
News Editor<br />
Features Editor<br />
Articles Editor<br />
Online Editor<br />
Copy Editors<br />
Special Sections Editors<br />
Yale Scientific<br />
M A G A Z I N E<br />
Established in 1894<br />
DECEMBER 2016 VOL. 90 NO. 1<br />
Production Manager<br />
Layout Editor<br />
Arts Editor<br />
Photography Editor<br />
Outreach Designer<br />
Webmaster<br />
Publisher<br />
Operations Manager<br />
Advertising Manager<br />
Subscriptions Manager<br />
Alumni Outreach Coordinator<br />
Synapse President<br />
Synapse Vice President<br />
Outreach Coordinators<br />
Social Media Coordinator<br />
Staff<br />
Sarah Adams<br />
Anushree Agrawal<br />
Kevin Biju<br />
Anusha Bishop<br />
Will Burns<br />
Claire Carroll<br />
Giorgio Caturegli<br />
Urmila Chadayammuri<br />
Kevin Chang<br />
Mary Chukwu<br />
Jasper Feinberg<br />
Krisstel Gomez<br />
Emma Green<br />
Advisory Board<br />
Kurt Zilm, Chair<br />
Priyamvada Natarajan<br />
Fred Volkmar<br />
Stanley Eisenstat<br />
James Duncan<br />
Stephen Stearns<br />
Jakub Szefer<br />
Werner Wolf<br />
John Wettlaufer<br />
William Summers<br />
Scott Strobel<br />
Robert Bazell<br />
Ayaska Fernando<br />
Ivan Galea<br />
Craig Crews<br />
Paul Han<br />
George Iskander<br />
Matthew Kegley<br />
Joe Kim<br />
Noah Kravitz<br />
Theo Kuhn<br />
Yanna Lee<br />
Danya Levy<br />
Joshua Mathew<br />
Charlie Musoff<br />
Grace Niewijk<br />
Eileen Norris<br />
Andrea Ouyang<br />
Lionel Jin<br />
Allison Cheung<br />
Zachary Gardner<br />
Sonia Wang<br />
Emma Healy<br />
Genevieve Sertic<br />
Amanda Buckingham<br />
Cheryl Mai<br />
Kendrick Umstattd<br />
Emily Boring<br />
Claire Kim<br />
Aviva Abusch<br />
Erin Wang<br />
Ashlyn Oakes<br />
Natalia Zaliznyak<br />
Cerys Holstege<br />
Newlyn Joseph<br />
Kevin Hwang<br />
Chunyang Ding<br />
Cheryl Mai<br />
Dawn Chen<br />
Kevin Biju<br />
Ruiyi Gao<br />
Stephanie Smelyansky<br />
Sarah Ludwin-Peery<br />
Uche Medoh<br />
Julia Wei<br />
Milana Bochkur-Dratver<br />
Lucinda Peng<br />
Jared Peralta<br />
Diane Rafizadeh<br />
Liz Ruddy<br />
Lauren Telesz<br />
Olivia Thomas<br />
Isa del Toro<br />
Jessica Trinh<br />
Edward Wang<br />
Laurie Wang<br />
Anna Wujciak<br />
Christine Xu<br />
Cynthia Yue<br />
Chemistry<br />
Astronomy<br />
Child Study Center<br />
Computer Science<br />
Diagnostic Radiology<br />
Ecology & Evolutionary Biology<br />
Electrical Engineering<br />
Emeritus<br />
Geology & Geophysics<br />
History of Science, Medicine & Public Health<br />
Molecular Biophysics & Biochemistry<br />
Molecular, Cellular & Developmental Biology<br />
Undergraduate Admissions<br />
Yale Science & Engineering Association<br />
Molecular, Cellular & Developmental Biology<br />
The Yale Scientific Magazine (<strong>YSM</strong>) is published four times a year<br />
by Yale Scientific Publications, Inc. Third class postage paid in New<br />
Haven, CT 06520. Non-profit postage permit number 01106 paid<br />
for May 19, 1927 under the act of August 1912. ISN:0091-287. We<br />
reserve the right to edit any submissions, solicited or unsolicited,<br />
for publication. This magazine is published by Yale College students,<br />
and Yale University is not responsible for its contents. Perspectives<br />
expressed by authors do not necessarily reflect the opinions of <strong>YSM</strong>.<br />
We retain the right to reprint contributions, both text and graphics,<br />
in future issues as well as a non-exclusive right to reproduce these<br />
in electronic form. The <strong>YSM</strong> welcomes comments and feedback.<br />
Letters to the editor should be under 200 words and should include<br />
the author’s name and contact information. We reserve the right to<br />
edit letters before publication. Please send questions and comments<br />
to ysm@yale.edu.
NEWS<br />
in brief<br />
Modeling Mars: Life-Supporting Earthquakes?<br />
By Isa del Toro M.<br />
IMAGE COURTESY OF WIKIPEDIA<br />
►A topography map of Mars with different<br />
color intensities indicating the depth<br />
of craters and highlighting areas of possible<br />
seismic activity on its surface.<br />
There’s a new hypothesis on the block related<br />
to the possibility of life on Mars. Research<br />
conducted by Sean McMahon of the Yale Geology<br />
and Geophysics department, in collaboration<br />
with John Parnell and Nigel Blamey,<br />
looks into Earth’s subsurface hydrogen levels<br />
and how these indicate potential microbial<br />
activity on Mars.<br />
Hydrogen serves as an energy source for<br />
certain types of organisms. Subsurface hydrogen<br />
gas is created on Earth due to the grinding<br />
of rocks along ancient earthquake fault<br />
lines. McMahon’s experiment sought to determine<br />
whether these gas levels were enough<br />
to have spurred microbial life. Using crushfast-scan,<br />
a technique that involves crushing<br />
rocks to expel the gas contained with them<br />
and measuring the released gas composition,<br />
the researchers concluded that the hydrogen<br />
contained in these rocks was sufficient to fuel<br />
anaerobic life on Earth. Many types of rocks,<br />
including the basalt found on Mars, can likewise<br />
create hydrogen, leading researchers<br />
to determine that quake activity on Mars<br />
could fuel microbial life. In 2018, NASA’s<br />
InSight mission will collect data concerning<br />
seismological activity on Mars. This data<br />
will allow the researchers to re-evaluate the<br />
“Marsquake” models they used in their conclusions<br />
and determine whether their models<br />
fit Mars’s actual surface.<br />
McMahon’s results are an exciting find.<br />
They shed light on another possibility of life<br />
on Mars, which would have important consequences<br />
on how we approach the idea of human<br />
activity on the Red Planet, as well as our<br />
understanding of how life came to be in the<br />
universe.<br />
The Gruber Cosmology Conference at Yale<br />
By Urmila Chadayammuri<br />
PHOTOGRAPHY BY URMILA CHADAYAMMURI<br />
►Professor Manuela Campanelli of<br />
the University of Rochester presents<br />
her pioneering simulations of black<br />
hole mergers.<br />
The third annual Gruber Cosmology<br />
Conference took place at Yale on October<br />
7th, honoring discoveries advancing our<br />
understanding of the universe. This year’s<br />
Gruber Prize recipients were Rainer Weiss,<br />
Kip Thorne, and Ronald Drever, the leading<br />
scientists on the LIGO collaboration, which<br />
made the groundbreaking discovery of<br />
gravitational waves. The conference began<br />
with a history of gravitational waves, after<br />
which Weiss explained how the LIGO project<br />
worked. Speakers also highlighted upcoming<br />
detectors in Europe, India and Japan, which<br />
aim to pinpoint the origin of gravitational<br />
waves.<br />
The afternoon session outlined the impact<br />
of the discovery. Thorne described the<br />
new science we can probe with the help of<br />
gravitational waves, from learning about how<br />
the very early universe grew, to understanding<br />
spinning and colliding black holes. Harvard<br />
radio astronomer Shep Doeleman closed the<br />
conference with prospects for how we can<br />
directly image black holes and their power as<br />
gravitational lenses, which bend light from<br />
sources behind them, to directly image black<br />
holes.<br />
The presenters all spoke of their work as a<br />
conversation across centuries with the father<br />
of general relativity, Albert Einstein. What<br />
would Einstein have said if he heard of the<br />
LIGO observation? Thorne guessed he would<br />
try understanding the black hole merger that<br />
caused it, while Weiss thought he would ask<br />
how the equipment worked. Doeleman took<br />
a step back. We knew general relativity was<br />
correct before the gravitational wave detection,<br />
he said, as GPS would not work without it. If<br />
we were to present a map app to Einstein, he<br />
would most likely wonder, “What is a phone?”<br />
6 Yale Scientific Magazine December 2016 www.yalescientific.org
in brief<br />
NEWS<br />
The Miller laboratory of Yale’s Department<br />
of Chemistry recently made a discovery<br />
in peptide catalysis that could change how<br />
we think about enzymes. This discovery<br />
capitalized on the laboratory’s previous<br />
discovery of two peptide catalysts. Enzymes,<br />
or protein catalysts, are characterized by high<br />
specificity. Alford, the study’s first author, and<br />
his colleagues demonstrated that two short<br />
peptides, which are comprised of protein<br />
building block called amino acids, can catalyze<br />
two distinct, complementary reactions called<br />
oxidation reactions. This remarkable capacity<br />
is presumably due to the synthetic peptide’s<br />
overall structure: by varying just a few key<br />
amino acids outside of the active site where the<br />
reaction takes place, the same active residue can<br />
switch between catalyzing two very different<br />
reactions. This control of catalytic activity by<br />
Shrinking Enzymes<br />
By Giorgio Caturegli<br />
modifying secondary structure is a hallmark<br />
of enzymes but has had limited application<br />
in organic synthesis. “This finding is a really<br />
interesting manifestation of what the [Miller]<br />
group tries to do…using tools that nature has<br />
to understand natural processes,” said Nadia<br />
Abascal, a coauthor. Synthetic reactions can<br />
be studied to gain insight into processes in<br />
nature, which may follow a similar mechanism<br />
to the reactions observed in this study.<br />
Especially notable is the fact that peptides<br />
are orders of magnitude smaller than<br />
enzymes, and their small size and precise<br />
control could allow for synthetic applications<br />
in pharmaceutical and materials research.<br />
The Miller group’s recent finding in peptide<br />
catalysis is important to both understanding<br />
natural biochemical processes and developing<br />
synthetic applications.<br />
PHOTOGRAPHY BY NATALIA ZALIZNYAK<br />
►Miller’s laboratory discovered two<br />
peptides that can catalyze two different<br />
reactions based on secondary<br />
structure and reaction conditions.<br />
A New Excuse for Playing Video Games?<br />
By Jasper Feinberg<br />
Imagine if video games were a key to<br />
improving learning. Yale psychiatry professor<br />
Bruce Wexler believes they are. A study found<br />
that a video game-based learning regimen<br />
called Activate, developed by Wexler, improved<br />
the test performance of 583 schoolchildren<br />
compared to those without the regimen and<br />
those with one-on-one tutoring. The curriculum<br />
includes computer games aimed at cognitive<br />
improvement and a five minute warm-up<br />
computer activity designed to prepare students<br />
for learning.<br />
The Activate program harnesses<br />
neuroplasticity. The structure of the brain<br />
is shaped after birth from environmental<br />
stimuli that reorganize neuronal connections.<br />
Activate stimulates areas of the brain often<br />
underdeveloped in children who grow up in<br />
poverty or have neurodevelopmental problems<br />
like attention deficit hyperactivity disorder<br />
(ADHD). To accomplish this, Wexler used<br />
neuroimaging studies to identify the regions<br />
of the brain corresponding to certain cognitive<br />
tasks. Wexler describes Activate as “a school<br />
lunch program for the brain” customized to each<br />
individual student.<br />
The social implications of this educational<br />
strategy are vast. First, Activate has the potential<br />
to close the achievement gap by helping students<br />
with different educational backgrounds. As a<br />
technology-based tool, it is cheaper than many<br />
current solutions. Wexler’s research is also an<br />
effective treatment for depression and, in some<br />
cases, ADHD.<br />
Going forward, C8 Sciences, a Yale startup<br />
dedicated to spreading Activate, hopes to<br />
increase awareness and continue improving<br />
the program. Activate has been translated into<br />
multiple languages, and appears primed to<br />
expand.<br />
IMAGE COURTESY OF BRUCE WEXLER<br />
►A student using Activate, a gamebased<br />
learning program shown to<br />
improve test performance, in her<br />
school’s computer lab.<br />
www.yalescientific.org<br />
December 2016<br />
Yale Scientific Magazine<br />
7
NEWS<br />
molecular biology<br />
BREATHE EASY<br />
New drug reduces lung cancer cell growth<br />
►BY EILEEN NORRIS<br />
Wouldn’t it be nice if killing lung cancer cells was as easy as<br />
flipping a switch? As it turns out, effectively targeting these<br />
cells is more like a dimmer rather than a switch, but it can<br />
be done, according to new research spearheaded by Joseph<br />
Contessa, associate professor of Therapeutic Radiology and<br />
Pharmacology at the Yale School of Medicine. Contessa led<br />
the discovery of a drug that reduces non-small cell lung cancer<br />
(NSCLC) tumor cell growth, proliferation, and survival,<br />
without causing toxic effects to healthy cells.<br />
NSCLC comprises about 80 to 85 percent of lung cancers and<br />
generally spreads more gradually than small cell lung cancer.<br />
Much cancer biology research surrounds the role of receptor<br />
tyrosine kinases (RTKs), cell surface receptor proteins, in the<br />
behavior of tumor cells. RTKs stimulate signals within cells<br />
that direct the cell to grow, divide, and proliferate, and can<br />
trigger survival signals in toxic environments. In cancer cells,<br />
RTK genes are overexpressed, causing more RTKs to appear<br />
on the cell surface, leading to more resilient and fastergrowing<br />
cancer cells.<br />
Contessa’s lab aimed to better understand how RTKs<br />
affect tumor growth and survival, and therefore explore how<br />
scientists can target these receptors to control tumors. Prior<br />
hypotheses extrapolate that if one can block the function of<br />
RTKs, turning them “off,” tumors can be treated with more<br />
success. Current drugs and compounds such as Gefitinib<br />
and Erlotinib target specific RTKs but do not work as well as<br />
hypotheses predict. Early in his research, Contessa postulated<br />
that these drugs failed due to redundant signaling, or the<br />
presence of dominant and backup receptors that all signal<br />
NSCLC tumor cell growth and proliferation. Therefore,<br />
drugs and compounds that only target one receptor are<br />
ineffective in treating the NSCLC tumor cells.<br />
Thus, Contessa looked for ways to target multiple<br />
receptors without creating a toxic environment for normal<br />
cells. He found that all of the receptors are glycoproteins—<br />
they have sugar chains attached to them. Contessa then<br />
hypothesized that by interrupting glycosylation—the<br />
addition of sugar chains—the function of the glycoprotein<br />
RTKs could be blocked.<br />
“What people thought before was that adding these sugar<br />
chains was a switch like a light switch, turning on and turning<br />
off. What we’ve shown is there’s actually a spot that you can<br />
hit it that’s more like a dimmer switch, where you can just<br />
turn it down. What we found is a small molecule, a drug-like<br />
compound, that can act this way—it can turn the dimmer<br />
switch down,” Contessa said.<br />
This drug, N-linked glycosylation inhibitor-1 (NGI-<br />
1), targets non-small cell lung cancer cells by inhibiting an<br />
enzyme that attaches sugar chains to RTK precursors and<br />
creates the mature glycoprotein RTKs. Contessa’s research<br />
showed that this drug reduces the expression of epidermal<br />
growth factor receptor (EGFR), a specific RTK, on the surface<br />
of the lung cell. In the drug-treated cells, the EGFRs were<br />
found inside of the cell, indicating that NGI-1 prevents the<br />
transport of RTKs to the cell surface.<br />
Contessa’s research further confirmed that NGI-1 is<br />
specific; although it inhibits RTK signaling, it does not<br />
inhibit the transport of all glycoproteins to the cell surface, so<br />
glycoproteins essential to healthy cell function are unaffected.<br />
“It means that tumor cells that are highly dependent on<br />
RTKs become very sensitive to this drug,” Contessa said.<br />
His research shows that NGI-1 arrests cellular growth and<br />
division in RTK-dependent NSCLC tumor cells.<br />
The project was not without difficulties. “The whole project<br />
was a challenge… it was a collaborative effort, and we worked<br />
with a couple different groups,” Contessa said. The process<br />
sounds easy—a step-by-step path towards a new method of<br />
battling lung cancer. In reality, this one drug resulted from<br />
five years of dedicated research and testing, screening over<br />
350,000 drugs.<br />
“You’re kind of on this detective hunt. You’re screening and<br />
you find this inhibitor, and then you don’t know exactly how<br />
it works. So you have to call on some expertise to help you,<br />
and then hopefully you get a little lucky and you figure out<br />
the mechanism and you can advance it to your experimental<br />
models,” Contessa reflected.<br />
Contessa’s detective mindset, along with the advice of<br />
many collaborators and a bit of luck, led the researchers<br />
to a potential drug candidate for battling NSCLC tumors.<br />
Contessa looks to translate their successes in laboratory cell<br />
models into successes in live animal tumor models, and we<br />
will hopefully see NGI-1 in future clinical studies.<br />
PHOTOGRAPHY BY JARED PERALTA<br />
►A member of Joseph Contessa’s lab at work at the Yale<br />
School of Medicine.<br />
8 Yale Scientific Magazine December 2016 www.yalescientific.org
computational biology<br />
NEWS<br />
SOLVING THE PROTEIN REPACKING PUZZLE<br />
Tinkering with the building blocks of life<br />
►BY KEVIN CHANG<br />
www.yalescientific.org<br />
IMAGE COURTESY OF WIKIMEDIA COMMONS<br />
►Before the advent of computational methods, biologists<br />
and biochemists had to rely on bouncing x-rays off of protein<br />
crystals in order to determine the 3D structure of a protein.<br />
Proteins play an important role in all life processes. From<br />
catalyzing reactions to protecting our body to supporting<br />
cell structure, proteins have a wide variety of functions<br />
based on each specific protein’s structure. Naturally-occurring<br />
proteins are perfectly evolved for their specific functions<br />
in each organism. Synthetically designed proteins,<br />
however, have the potential to solve the multitude of global<br />
problems facing the world today. For example, engineered<br />
bacteria can make enzymes that help decompose plastics<br />
and reduce landfill waste, or produce designer proteins that<br />
can harvest energy from sunlight for clean energy.<br />
Direct experimental methods for designing synthetic<br />
proteins can be used for creating new proteins with the<br />
desired activities, but they are expensive and labor intensive.<br />
Another strategy is to employ computer simulations,<br />
which have the potential to greatly streamline the process<br />
and reduce costs. However, despite a number of successes,<br />
computational protein design software still frequently<br />
makes inaccurate predictions of protein structure and interactions.<br />
To solve this problem, two Yale groups are combining<br />
their expertise in an interdisciplinary effort led by Corey<br />
O’Hern, an associate professor of Mechanical Engineering<br />
& Materials Science, and Lynne Regan, a professor of Molecular<br />
Biophysics & Biochemistry and Chemistry.<br />
In a recent Protein Engineering, Design, and Selection<br />
paper published in July 2016, the team of researchers described<br />
a new computational model that helps solve the<br />
“repacking” problem, allowing them to accurately predict<br />
how each amino acid side chain fits into the core of a protein.<br />
Amino acids are the fundamental building blocks of<br />
proteins, so understanding how they are positioned within<br />
proteins is crucial to understanding protein structure. “It<br />
may sound trivial, but it is not because you have to try all<br />
side chain conformations to determine which one will fit.<br />
Our simple model performed as well as the state of the art<br />
software in repacking amino acid side chains,” O’Hern said.<br />
Other approaches include all possible energetic contributions<br />
to protein structure, such as steric interactions, electrostatic<br />
effects, van der Waals attractions, and hydrogen<br />
bonding. In contrast, the O’Hern and Regan team used a<br />
somewhat unconventional approach to modeling proteins<br />
by only considering steric interactions—repulsive forces<br />
that prevent atomic overlaps. In their approach, the amino<br />
acids are modeled as 3D puzzle pieces that are arranged to<br />
fit into the protein core without overlaps. The model can<br />
accurately predict how each amino acid must be positioned<br />
to best fit into the core, just like the way Tetris pieces in<br />
the 1980s video game need to be in certain orientations to<br />
tightly fit together and not overlap.<br />
“Our intention was to determine how far we could go in<br />
protein structure prediction using the simplest model and<br />
only add in additional factors when the simplest model can<br />
no longer predict the experimentally observed data. That<br />
was our idea: a bottom-up approach rather than throwing<br />
everything in at the beginning,” Regan said. “Surprisingly,<br />
we found that our model performs extremely well simply<br />
by avoiding steric overlaps. We didn’t need to explicitly put<br />
in any attraction or hydrogen bonding [or other factors].”<br />
The team discovered that their simple model worked well<br />
on many more amino acids than they anticipated. Even<br />
so, they were able to identify its limits and simultaneously<br />
learn much about the dominant forces that determine protein<br />
structure. This point is well illustrated by comparing<br />
the two hydroxyl functional group-containing amino acids,<br />
threonine and serine, which are typically considered<br />
similar in biochemistry textbooks. Although the position<br />
of the threonine side chain can be predicted by steric interactions<br />
alone, inclusion of hydrogen bonding is required to<br />
correctly position the serine side chain. O’Hern and Regan<br />
propose that this is because the steric interactions of the<br />
additional methyl group on threonine are dominant.<br />
The team has already expanded their original studies to<br />
successfully repack multiple amino acid side chains simultaneously,<br />
and they are working on calculating the energetic<br />
cost of mutating amino acids in protein cores and at<br />
interfaces. The O’Hern and Regan team are poised to apply<br />
their novel approach and combined expertise to design<br />
proteins for sustainability, biomedical, and pharmaceutical<br />
applications.<br />
December 2016<br />
Yale Scientific Magazine<br />
9
NEWS<br />
materials science<br />
SOLAR CELLS<br />
Organic solar cells reach new heights in efficiency<br />
►BY JOE KIM<br />
The old solar cell revolution has come to a halt. The types<br />
of solar cells that are now widespread were commercialized<br />
more than 50 years ago. Despite scientific improvements and<br />
increased attention to solar energy, the cost of conventional<br />
solar cells remains high due to the high cost of silicon, which<br />
converts solar energy into electric energy by producing<br />
electrons when light hits the silicon layer in the solar cell.<br />
Understanding the negative effects of fossil fuels and the<br />
necessity for cheaper renewable energy, scientists have worked<br />
on engineering new solar cell designs using different materials.<br />
Currently, in contrast to the inorganic solar cells that dominate<br />
the field, organic polymer solar cells have been getting much<br />
attention due to their mechanical flexibility, large area, light<br />
weight, and low costs in mass-scale production. Organic<br />
polymer solar cells differ in that carbon-based polymer is used,<br />
and not the conventional silicon. The main hurdle that many<br />
researchers face in developing organic polymer solar cells is<br />
their low efficiency. Although slow improvements have been<br />
made, the most common design, single-junction cells with<br />
only one electron-producing active layer, has only an eight<br />
to ten percent power conversion efficiency—far less than the<br />
commercially required efficiency of over 20 percent.<br />
Recently, researchers in professor Andre Taylor’s<br />
transformative materials and devices lab broke through the<br />
10 percent boundary by incorporating multiple cocrystalline<br />
squaraines into the solar cell’s active layer. These cocrystalline<br />
squaraines are organic fluorescent dyes that absorb light<br />
and produce electrons, which are then picked up by the<br />
interlayer to produce a current. Tenghooi Goh, a recent PhD<br />
graduate, explained that their new design, which contains a<br />
greater number of electron donors, allows the solar cell to<br />
absorb a wider range of wavelengths, or types of light. Typical<br />
polymer cells only absorb specific types of light and waste<br />
the light outside that range, resulting in decreased efficiency.<br />
However, Goh said that incorporating more materials is<br />
extremely complicated, as undesirable interactions between<br />
incompatible chemicals can occur. “Mixing things are not as<br />
simple and direct as it may suggest. In a lot of times, if you<br />
mix two incompatible things together…they actually drive<br />
down the efficiency instead of having a positive effect,” Goh<br />
said. Even with the setback, Goh stated this was a path to a<br />
fundamental breakthrough in organic polymer solar cell<br />
efficiency. Thus, the researchers focused on minimizing this<br />
potential destructive interaction.<br />
Previously, Goh and Taylor’s team successfully combined<br />
squaraine and high efficiency polymer component, thanks<br />
to certain properties of the system. Chromophores, or lightsensitive<br />
molecules, transfer energy between an acceptor<br />
and donor molecule through Förster resonance energy<br />
transfer (FRET). Goh referred to FRET as “a mechanism like<br />
photosynthesis, with electrons jumping over non-conducting<br />
gaps.” Therefore, FRET stabilized the final mixture by allowing<br />
energy to be transferred between materials, ultimately helping<br />
the team mix together potentially incompatible components<br />
so that the wide wavelength of light was preserved. The energy<br />
transfer between two squaraines, ASSQ and DPSQ, along with<br />
high performance electron donating compounds in active<br />
layers, helped stabilize the final mixture in the active layer.<br />
The team found that photovoltaic efficiency increased<br />
by over 25 percent on average between solar cells with and<br />
without ASSQ and DPSQ incorporated. In addition, multiple<br />
FRET pairs with rapid and efficient energy transfer were<br />
observed through spectroscopy techniques, which measures<br />
rapid changes in the absorbance of certain wavelengths of light.<br />
Such observations corresponded with the abovementioned<br />
explanation validating that FRET was indeed responsible for<br />
the stable combination of components.<br />
The solar cells have their shortcomings—Goh pointed<br />
out that the organic polymer solar cells are not free from<br />
environmental consequences such as harmful solvent waste.<br />
Even so, this research can provide greater benefits by lowering<br />
costs of production, leading to more widespread usage of<br />
solar cells and decreased fossil fuel usage. The efficiency of<br />
Goh’s team’s solar cell was recorded to be up to 10.7 percent,<br />
widely considered a milestone in efficiency of organic polymer<br />
solar cells. Furthermore, he added that this is before efficiency<br />
optimization by researching and modifying the layers<br />
surrounding the active cell. Goh is very hopeful about future<br />
research. “In the future, if we combine the pinnacle of different<br />
research together, we can probably reach greater efficiency.”<br />
PHOTOGRAPHY BY JOSHUA MATHEW<br />
►Research in Andre Taylor’s lab focuses on organic solar cells, which<br />
consist of thin films with unique light-absorbing and energy-transfer<br />
properties that allow them to harness solar energy more efficiently.<br />
10 Yale Scientific Magazine December 2016 www.yalescientific.org
medicine<br />
NEWS<br />
THE FLU SEASON CRAVINGS PARADOX<br />
The connection between metabolism and disease outcome<br />
►BY MARY CHUKWU<br />
www.yalescientific.org<br />
PHOTOGRAPHY BY CHUNYANG DING<br />
►Yale researchers in Professor Ruslan Medzhitov’s lab found<br />
connections between metabolism and infection that may lead to<br />
new approaches to nutrition for the critically ill.<br />
As winter settles in, perhaps the only seasonal “foods” more iconic<br />
than hot chocolate and s’mores are cough drops and tea. Why do<br />
some people want to weather colds holding steaming bowls of comforting<br />
soup, while others suffer queasy stomachs and leave dinner<br />
plates untouched? The seemingly paradoxical appetite changes associated<br />
with sickness are a well-recognized and evolutionarily ancient<br />
trait, but up until now scientists could only speculate about<br />
their cause and purpose.<br />
Yale researchers led by Ruslan Medzhitov, professor of immunobiology<br />
at the Yale School of Medicine, have found that the answer<br />
to this puzzle lies with the causes of infection. The key insight of<br />
their research is that not all sicknesses are created the same. Fighting<br />
viral versus bacterial infections requires completely opposite<br />
nutritional needs. The findings of their research hold the potential<br />
to transform how healthcare approaches nutrition in illness.<br />
The researchers began by tracing out how anorexia, or loss of appetite,<br />
affects disease outcome in bacterial infections. Researchers<br />
infected mice with Listeria monocytogenes, a common cause of<br />
food poisoning. Mice that were fed during infection died; those<br />
who did not eat lived.<br />
Similarly, the researchers infected mice with influenza virus, the<br />
cause of the flu, and again varied caloric intake. Now the fortunes<br />
were reversed: fed mice survived viral infection while those that did<br />
not eat mostly died. These trends held true not only for infection<br />
but also when the experiments were repeated for bacterial and viral<br />
inflammation—whole body immune activation.<br />
The real story linking nutrition and disease, however, emerged in<br />
the search for the nutrient causing the outcomes. Between protein,<br />
fat, and glucose, only glucose was required to induce the complete<br />
effects of caloric intake. Moreover, blocking glucose utilization rescued<br />
bacteria-infected mice while killing virus-infected mice.<br />
Interestingly, glucose does not change the number of pathogens<br />
or the strength of the immune response. Instead, glucose<br />
shapes the role of metabolism in the body’s tolerance of the immune<br />
response. Metabolism refers to all the chemical reactions<br />
needed to sustain life; use of the immune system comes at a price.<br />
“Depending on the type of inflammation or infection, there<br />
are different metabolic processes that are necessary to survive the<br />
critical illness condition,” Medzhitov explained. Specifically, bacterial<br />
and viral infections generate different kinds of tissue damage<br />
depending on the presence of glucose.<br />
While glucose dominates metabolism in the fed state, during<br />
a fasting state the body begins breaking down fat stores to utilize<br />
molecules called ketone bodies for energy. Bacterial infections<br />
cause an immune response that releases reactive oxygen species<br />
(ROS), or “free radicals,” which kill pathogens as well as damage<br />
host cells. Glucose exacerbates this negative side effect while ketone<br />
bodies from starvation are protective. A parallel exists for<br />
viral infection.<br />
In response to the cellular damage caused by viral infection,<br />
the unfolded protein response (UPR) targets and eliminates cells<br />
producing abnormal proteins. This process is regulated by glucose—without<br />
glucose, this stress-induced response leads to excessive<br />
cell damage.<br />
“We discovered that by blocking glucose utilization in viral infections<br />
we prevented a normal response against viruses and instead<br />
caused a response that ended up being destructive for the<br />
host,” said Andrew Wang, first author and clinical fellow in medicine.<br />
Shockingly enough, the battleground where glucose decided<br />
life and death was not in the heart or the lungs, as may be expected<br />
for a pulmonary illness like the flu, but rather in the brain.<br />
PET scans and tissue studies revealed damage at critical sites in<br />
the brain following bacterial and viral infection. Absence of glucose<br />
increased neuronal damage in viral infections while for bacteria<br />
the opposite was true. The damage was once again linked to<br />
either overactivity of the UPR or overproduction of ROS.<br />
Medzhitov and his team hope that these new findings can<br />
improve nutrition for the acutely ill. Currently, all ICU patients<br />
are fed intravenous liquid food that is 30 to 60 percent carbohydrates,<br />
but Medzhitov’s study suggests that these formulations<br />
need to be adjusted based on the cause of illness. The Yale<br />
team is currently preparing clinical trials that test that premise.<br />
Future studies by the team will continue using mouse models<br />
to study different types of infections, including parasitic and<br />
fungal. Their work will contribute to new holistic models of<br />
healthcare treatment.<br />
“The general implication is that there is a certain wisdom<br />
to the body’s reactions and our preferences during illness, and<br />
many of these are protective,” Medzhitov said. In sickness at<br />
least, we can all benefit from listening to our bodies.<br />
December 2016<br />
Yale Scientific Magazine<br />
11
A ROCKY ROAD<br />
TO THE PAST<br />
BY KEVIN BIJU<br />
ART BY EMMA HEALY<br />
TWO HUNDRED AND<br />
FIFTY TWO MILLION<br />
YEARS AGO, THE WORLD<br />
WAS ENGULFED IN A<br />
NIGHTMARISH SCENARIO<br />
AKIN TO WHAT WE<br />
FEAR TODAY.
environmental science<br />
FOCUS<br />
Surging carbon dioxide levels,<br />
combined with increased radiation<br />
from the Sun, dramatically increased<br />
global temperatures. Ocean surface<br />
temperatures reached upwards of 104<br />
degrees Fahrenheit. Consequently, mass<br />
extinctions occured, with marine and<br />
terrestrial life suffering huge losses in<br />
biodiversity.<br />
Until now, the scientific community<br />
has struggled to determine the relative<br />
importance of the two forces that drove<br />
the Permian-Triassic mass extinction<br />
event: volcanic activity and erosion. A<br />
study led by Ryan McKenzie, a postdoctoral<br />
associate at the Yale Department<br />
of Geology and Geophysics, has now<br />
proposed a solution. The study argues<br />
that on the time scale of the past several<br />
hundred million years, volcanoes have<br />
been the principal driver of climate<br />
change. These revolutionary findings are<br />
key to understanding long-term climate<br />
change, and thus, may prove informative<br />
in our present-day combat against global<br />
climate change.<br />
The greenhouse effect<br />
Carbon dioxide (CO 2<br />
) is a double-edged<br />
sword—both vital to life yet potentially<br />
harmful. On one hand, much of Earth’s<br />
plant life depends on CO 2<br />
to produce<br />
food for itself and consumers, like us. At<br />
the same time, increasing CO 2<br />
levels since<br />
the industrial revolution have led to rising<br />
global temperatures, which pose a risk<br />
to the global ecosystem. How does this<br />
happen?<br />
The Earth’s atmosphere normally<br />
reflects much of the Sun’s invisible<br />
infrared radiation back into space,<br />
thereby preventing surface temperatures<br />
from becoming too high. However,<br />
when sufficiently concentrated in the<br />
atmosphere, CO 2<br />
can form a blanket of<br />
sorts, which traps some of this radiation<br />
and prevents it from leaking back to space.<br />
Thus, CO 2<br />
is aptly termed a greenhouse<br />
gas.<br />
Various processes regulate the levels<br />
of CO 2<br />
in the atmosphere. Volcanic<br />
eruptions, which release gases from the<br />
Earth’s interior, contribute to atmospheric<br />
greenhouse gases and raise global<br />
temperature levels. Chemical weathering,<br />
on the other hand, has the opposite<br />
effect. When CO 2<br />
reacts with water vapor,<br />
carbonic acid is formed. This weak acid<br />
then eats away at rocks and other surfaces.<br />
Other forms of chemical weathering<br />
include burial of carbonate minerals,<br />
along with burial of organic carbon. Thus,<br />
chemical weathering is a CO 2<br />
sink and has<br />
the ultimate impact of decreasing global<br />
temperatures.<br />
The scientific community recognizes<br />
these two forces—volcanism and<br />
weathering—as the principal drivers of<br />
long-term climate change. Due to these<br />
two processes oscillating and changing<br />
pace over time, the content of CO 2<br />
in the<br />
atmosphere is in constant flux. Thus, the<br />
Earth’s temperature has risen and fallen<br />
multiple times within its history, creating<br />
various periods of global warming<br />
followed by global cooling in the form of<br />
ice ages.<br />
The unearthing begins<br />
The study began with McKenzie’s<br />
fascination with the links between climate<br />
change and biodiversity. “I became<br />
interested in the anomalies characteristic<br />
of the Cambrian period,” McKenzie said.<br />
“A lot of species extinction occurred,<br />
which many people attribute to the<br />
Cambrian having one of the highest<br />
atmospheric carbon dioxide levels of the<br />
past six hundred million years.” McKenzie<br />
set out to discover the root cause of this<br />
carbon dioxide flux.<br />
First, McKenzie and team needed to<br />
obtain a record of Earth’s volcanic history.<br />
The Earth is made up of multiple tectonic<br />
plates, which are large pieces of the Earth’s<br />
crust. When an oceanic plate collides<br />
with a continental plate, a subduction<br />
zone is formed. The oceanic plate sinks<br />
deeper into the earth, liberating water in<br />
the process. This water gradually seeps<br />
upward, melting the hot mantle rocks<br />
and forming magma in the process.<br />
This magma finally rises to the surface<br />
and forms a chain of active volcanoes.<br />
Unfortunately, however, it is often difficult<br />
to track the formation of these volcanic<br />
emissions through Earth’s history because<br />
erosion and destruction of volcanoes<br />
obscures the important data. In addition,<br />
the commonly used sea-level approach to<br />
track volcanic rates through time relies<br />
on too many vague assumptions. This is<br />
where zircons come in.<br />
Zircons, otherwise known as zirconium<br />
silicate, are grains of sedimentary rocks<br />
that crystallize from magma. Young zircon<br />
is especially prevalent in the subduction<br />
zones of continental volcanoes, such as the<br />
Andes and the Cascade volcanoes. Zircon<br />
grains are able to withstand high degrees<br />
of erosion, so they represent untampered<br />
records of volcanic activity. Fortunately,<br />
due to zircon’s uranium impurities, the<br />
age of zircon samples can be determined<br />
very precisely through radioactive<br />
isotope analysis. Thus, if one can trace an<br />
abundance of young zircon to a specific<br />
period, this period likely experienced<br />
massive continental volcanic activity.<br />
McKenzie and his team used this property<br />
of zircon to contribute to a precise record<br />
of continental volcanic activity throughout<br />
the geologic timeline. The team could now<br />
accurately map the relationships between<br />
carbon dioxide levels and volcanic activity.<br />
IMAGE COURTESY OF RYAN MCKENZIE<br />
►Dr. Ryan McKenzie stands with a fuming<br />
Mt. Bromo in Indonesia. McKenzie analyzed<br />
sedimentary rock to more closely link volcanic<br />
emissions to long-term climate change driven<br />
by carbon dioxide concentration.<br />
www.yalescientific.org<br />
December 2016<br />
Yale Scientific Magazine<br />
13
FOCUS<br />
environmental science<br />
Mapping the Earth<br />
IMAGE COURTESY OF RYAN MCKENZIE<br />
►Shown is a photo of Mt. Vesuvius in<br />
Italy. Data on sedimentary rocks in the<br />
area contributed to McKenzie’s analysis of<br />
volcanic activity.<br />
“In addition to the scientific literature,<br />
we did extensive work in India, Myanmar,<br />
and North China to fill in the existing gaps<br />
within zircon data sets,” McKenzie said.<br />
Compiling analyses of close to 120,000<br />
zircons, McKenzie’s team found a promising<br />
pattern. The Cambrian, Jurassic, and<br />
Cretaceous periods, which saw high levels<br />
of CO 2<br />
, had very high proportions of young<br />
zircons. In contrast, the Neoproterozoic,<br />
Carboniferous, early Permian, and<br />
Cenozoic periods, when CO 2<br />
levels were<br />
low, had low proportions of young zircons.<br />
“We were able to establish a crucial link<br />
between the oscillations of volcanic gas<br />
activity and the flux of greenhouse gas<br />
levels,” McKenzie said.<br />
The findings of this study fit well into the<br />
geographic framework of continental shifts.<br />
Multiple times throughout Earth’s history,<br />
continents have rifted and amalgamated.<br />
Rifting periods—times when continents<br />
separate from each other—create extensive<br />
subduction zones, which in turn fuel<br />
continental volcanic activity, increasing<br />
zircon and CO 2<br />
abundance. On the other<br />
hand, amalgamation periods—times when<br />
two continents combine—lead to a loss of<br />
subduction zones, reducing volcanic activity<br />
and therefore zircon and CO 2<br />
abundance.<br />
Thus, the results of McKenzie’s study<br />
could be verified by existing knowledge<br />
about continental shifts. Ultimately, the<br />
techniques used in this project provide<br />
strong proof of the versatility of zircon as<br />
an indicator of volcanic CO 2<br />
emissions.<br />
Thus, with this innovative zircon<br />
technique, McKenzie’s team has provided<br />
compelling evidence that volcanism has<br />
been an important driver of climate change<br />
over the past 700 million years. “Many of<br />
the specialists in this field were initially<br />
skeptical of this work, so we faced the<br />
challenge of revising popular opinion,”<br />
McKenzie said. While McKenzie and his<br />
group have primarily focused on volcanism<br />
as a key driver, they still recognize the<br />
importance of weathering in contributing<br />
to CO 2<br />
changes. However, they argue that<br />
weathering can be interpreted simply as a<br />
secondary effect of volcanoes. Volcanoes<br />
contribute the primary influx of CO 2<br />
into<br />
the atmosphere, so they exert the greatest<br />
first-order control over long-term climate<br />
change.<br />
However, volcanoes do not just act in one<br />
direction. Volcanoes result in both global<br />
warming and global cooling. According<br />
to other studies, a fuller consideration of<br />
the effect of volcanism on climate change<br />
must include the long-term effects of<br />
volcanic rocks. Indeed, volcanic activity<br />
can certainly lead to immediate increases<br />
in CO 2<br />
emissions, leading to higher<br />
temperatures. However, during periods of<br />
volcanic dormancy, the volcanoes can be<br />
weathered. This weathering removes great<br />
quantities of CO 2<br />
from the atmosphere,<br />
leading to a global cooling events. Thus,<br />
if considered on a long-term time scale,<br />
each volcano is both a carbon source and<br />
a carbon sink. Indeed, volcanism is a major<br />
force that regulates long-term climate<br />
change.<br />
Future digs<br />
Modern-day, human-driving global<br />
warming is a formidable challenge,<br />
especially given the jump in CO 2<br />
emissions<br />
in such a short period of time. But placing<br />
ourselves in geological time, we would see<br />
that global warming has occurred multiple<br />
times since the formation of the Earth’s<br />
atmosphere as CO 2<br />
levels oscillated with<br />
the rise and fall of continental volcanic<br />
activity. Global warming has defined the<br />
landscape of existing biodiversity and<br />
geography on Earth, notably during the<br />
Permian-Triassic extinction when 70<br />
percent of land species and 90 percent of<br />
marine species went extinct. Importantly,<br />
global warming of the past educates us on<br />
the critical interactions that occur between<br />
carbon sources and carbon sinks, which<br />
is a part of present-day human-driven<br />
climate change as well as the climate<br />
variation of the past.<br />
Moving forward, McKenzie’s research<br />
group refuses to be constrained to<br />
one specific goal. “Up until now, the<br />
constraints of our data have been limited,”<br />
McKenzie said. “We hope to look at more<br />
high-resolution data sets and put more<br />
real numbers to this data.” Indeed, to fully<br />
uncover the Earth’s rich history, we must<br />
be willing to constantly dig deeper.<br />
ABOUT THE AUTHOR<br />
KEVIN BIJU<br />
KEVIN BIJU is a sophomore Molecular Biophysics and Biochemistry major in<br />
Morse College. He is the Alumni Outreach Coordinator of the Yale Scientific<br />
Magazine and is interested in the cross-talk between evolution and genetics in<br />
biomedical research.<br />
THE AUTHOR WOULD LIKE TO THANK Dr. Ryan McKenzie for his thoughtful<br />
interview, as well as his research team’s dedication.<br />
FURTHER READING<br />
M. R. Burton, G. M. Sawyer, D. Granieri Deep carbon emissions from<br />
volcanoes. Rev. Mineral. Geochem. 75, 323–354 (2013).<br />
14 Yale Scientific Magazine December 2016 www.yalescientific.org
STICKING<br />
IT TO<br />
CANCER<br />
FIGHTING<br />
TUMORS WITH<br />
NANOPARTICLES<br />
BY JESSICA TRINH<br />
ART BY<br />
LAURIE WANG<br />
www.yalescientific.org<br />
December 2016<br />
Yale Scientific Magazine<br />
15
FOCUS<br />
biomedical engineering<br />
Eyes on the prize, you jump into a river, furiously swimming for the shoreline.<br />
Yet, the second you reach for it, the current pulls you away. This is the<br />
challenge cancer drugs face in the human body: rapid clearance from the<br />
treatment site. The protection and safe delivery of these drugs as they travel<br />
to their target region are important factors in the drug’s success.<br />
In order to combat this problem of rapid<br />
clearance, a group of Yale researchers<br />
has been studying therapeutic drug delivery<br />
through the use of sticky biodegradable<br />
nanoparticles. This technique targets tumors<br />
more efficiently by releasing drugs directly<br />
into the cancerous regions. The Yale study<br />
found that bioadhesive nanoparticles were<br />
capable of remaining in the tumor regions for<br />
long periods of time, demonstrating the potential<br />
for drug delivery through nanoparticles<br />
to fight cancer.<br />
Promising potential<br />
Surgery and chemotherapy are common<br />
treatments for aggressive tumors arising from<br />
the ovary and uterus. Unfortunately, many<br />
patients undergoing these therapies redevelop<br />
tumors or, in the case of chemotherapy,<br />
see their tumors become resistant to the<br />
treatment. For a little over the past decade,<br />
nanoparticles have emerged as a delivery<br />
system for agents such as drugs, targeting a<br />
larger portion of the drug to the tumor and<br />
causing less severe side effects. Nanoparticles<br />
can be engineered to enclose these drugs,<br />
protecting them on their way to the target site<br />
in the body.<br />
Nanoparticle size plays an important role in<br />
the drug’s ability to stay in the region of the<br />
tumor. Too large a particle results in the drug’s<br />
accumulation in the lower abdomen, while<br />
too small of a particle results in a greater<br />
chance of abdominal fluid clearing the drug<br />
out of the system. With successful control<br />
of nanoparticle size, however, nanoparticles<br />
have the potential to allow for safer and more<br />
effective cancer treatment.<br />
A sticky finding<br />
Mark Saltzman, a professor at the Yale<br />
School of Engineering and Applied Science,<br />
is working to harness the potential<br />
of nanoparticles. His team developed<br />
nanoparticles with an outer coating of a<br />
polymer known as hyperbranched polyglycerol<br />
(HPG). HPG nanoparticles are like<br />
branched trees, where each branch is terminated<br />
in water-loving groups that make the<br />
particles water-soluble. This specific HPG<br />
outer coating has proven to be more effective<br />
than even the most highly regarded<br />
particle coating, possessing higher stability,<br />
lower risk of absorption in the body by proteins,<br />
and longer circulation in blood.<br />
Experimenting with nanoparticles of<br />
different sizes, the team found nanoparticles<br />
measuring around 100 nanometers to<br />
be most effective in distributing throughout<br />
the body cavity and dispensing their<br />
encapsulated drug to the target site. The<br />
longer the time in the body, the longer the<br />
nanoparticles will release the therapeutic<br />
drugs into the tumors.<br />
Initially, Saltzman and his laboratory<br />
team worked with non-sticky nanoparticles<br />
that would circulate around the body<br />
for extended periods of time and eventually<br />
accumulate in the tumor. However, Yang<br />
Deng, a postdoctoral associate working in<br />
the laboratory, had an interesting finding.<br />
With organic chemistry techniques, he was<br />
able to make the nanoparticles that stick to<br />
protein-coated surfaces. This was done by<br />
using sodium periodate to transform the<br />
outer coating of the particles, generating<br />
aldehyde groups which are able to form<br />
bonds with other proteins.<br />
Once the team discovered these sticky<br />
particles, the race was on to find suitable<br />
applications. The team was able to invent<br />
a new kind of sunblock that lasted longer<br />
on the skin, taking advantage of how the<br />
nanoparticles could stick to the skin’s top<br />
layer. However, the researchers also realized<br />
they could apply these sticky nanoparticles<br />
to areas such as cancer treatment. This is<br />
where Alessandro Santin came in.<br />
Alessandro Santin, a professor at the Yale<br />
School of Medicine, treats patients with gynecological<br />
tumors with origins in the uterus<br />
and ovaries. In some cases, the tumor<br />
spreads out of the reproductive tract and<br />
into the abdomen, where it would grow in<br />
PHOTOGRAPHY BY GEORGE ISKANDER<br />
►A member of the Saltzman lab prepares<br />
reagents for her experiment. The Saltzman<br />
lab has pioneered the use of nanoparticles<br />
for drug delivery.<br />
little clusters of cells that stick to the membrane<br />
surfaces of the abdomen.<br />
Saltzman believed his sticky nanoparticles<br />
were relevant to Santin’s work for<br />
a variety of reasons. “If they’re sticky,<br />
we thought they would stick to the same<br />
membranes that the cancer cells stick to<br />
and they should get all over the abdomen,<br />
and eventually stick to the same surfaces<br />
tumor cells stick to,” Saltzman said.<br />
Saltzman and his team hypothesized that<br />
the sticky nanoparticles they had created<br />
could be applied to deliver drugs to tumors.<br />
16 Yale Scientific Magazine December 2016 www.yalescientific.org
iomedical engineering<br />
FOCUS<br />
Targeting tumors with drugs<br />
Saltzman, Santin, and their team sought<br />
to apply the their invention to cancer therapy.<br />
First, they tested how adhesive the sticky<br />
nanoparticles were compared to nonadhesive<br />
nanoparticles. To do this, they tested both<br />
particles in human umbilical cords, measuring<br />
how long they remained on the luminal<br />
surface. As a marker to quantify the level of<br />
adhesiveness, both particles were loaded with<br />
a dye, which emitted a fluorescent signal corresponding<br />
to the amount of particles in the<br />
region. The results showed that the bioadhesive<br />
nanoparticles had a longer signal time<br />
than that of their non-sticky counterparts.<br />
Now, the researchers could proceed with<br />
loading a drug into these nanoparticles.<br />
Epothilone B (EB), a drug that inhibits<br />
microtubule function, can prevent cancer<br />
cell division . The researchers chose to load<br />
EB into these sticky nanoparticles because<br />
of its efficacy against both ovarian and uterine<br />
cancers. However, the drug comes with<br />
its dangers. “The problem with this drug is<br />
that it’s so potent at killing cancer cells that<br />
it’s toxic,” Saltzman said. Therefore, a way<br />
to introduce the drug to the cancerous region<br />
gradually and more directly is crucial.<br />
Saltzman hypothesized that by injecting<br />
these EB-loaded bioadhesive nanoparticles<br />
into the space between the membranes that<br />
line the abdominal cavity, they could get<br />
the nanoparticles to form bonds with the<br />
proteins on the tissue surfaces. This would<br />
increase the length of time over which drug<br />
would be delivered to the tissue.<br />
Traditionally, nanoparticles injected in<br />
this manner would be quickly cleared from<br />
the abdominal region. With the bioadhesive<br />
nanoparticles, however, the protein bonds<br />
formed with the cells layering this region<br />
held the nanoparticles in place. “We showed<br />
that if you take the particles and you expose<br />
them to a protein-coated surface, they stick<br />
very well,” Saltzman said. If successful, this<br />
would increase the bioavailabilty of the drug.<br />
To test if this indeed happened, the researchers<br />
created a mouse model with human<br />
tumors in the abdominal region to simulate<br />
the environment in a human cancer<br />
patient. They loaded EB into the nanoparticle<br />
vectors and injected them into the mice.<br />
The results were promising: at the end of four<br />
months, the mice subjected to this treatment<br />
had a 60 percent survival rate, whereas only<br />
10 percent of mice survived in the control<br />
groups. “We showed that by putting it in our<br />
bioadhesive nanoparticles, we can keep it in<br />
the abdomen for a long time with very little<br />
toxicity, particularly compared to the drug<br />
itself,” Saltzman said.<br />
Sticking with it<br />
The results of the Yale study offer the potential<br />
for more efficient methods for delivering<br />
drugs to target tumor cells. In the<br />
future, the researchers hope to increase the<br />
efficiency of drug delivery. For example, Santin<br />
is working on designing homing peptides<br />
that would target tumors specifically. “Doing<br />
so may increase the antitumor activity of the<br />
nanoparticle treatment,” Santin said.<br />
Yet, more research needs to be done on the<br />
deliver system used in the study. Saltzman<br />
states that the researchers did not see a specific<br />
immune response when they observed<br />
general markers of immune activation, but<br />
that there are still more areas of concern to<br />
be addressed before the drug delivery system<br />
is ready to be used for cancer patient treatment.<br />
According to Santin, the researchers<br />
are working on an investigator-initiated trial<br />
using the drug. “This clinical trial will help to<br />
understand the potential of this novel agent<br />
in the treatment of chemotherapy-resistant<br />
ovarian cancer,” Santin said.<br />
The results of the team’s work indicate the<br />
potential for bioadhesive nanoparticles as<br />
drug delivery agents to cancerous tumors.<br />
With more research on safer cancer treatment<br />
methods, nanoparticles may become a<br />
powerful weapon in our arsenal against devastating<br />
cancers.<br />
ABOUT THE AUTHOR<br />
JESSICA TRINH<br />
JESSICA TRINH is a freshman and prospective biomedical engineering major<br />
in Branford. She enjoys volunteering for Synapse, Yale Scientific’s volunteer<br />
outreach program, being the Director of Operations for Resonance, Yale<br />
Scientific’s high school outreach program as well as the Communications<br />
Chair for Yale’s chapter of STEAM.<br />
THE AUTHOR WOULD LIKE TO THANK Dr. Mark Saltzman and Dr.<br />
Alessandro Santin for their time and enthusiasm.<br />
www.yalescientific.org<br />
December 2016<br />
Yale Scientific Magazine<br />
17
CANINES ARE OVER<br />
OVERIMITATION<br />
BY ANNA WUJCIAK | ART BY OLIVIA THOMAS<br />
When, as a child, we were learning<br />
to tie our shoes, we painstakingly<br />
followed the directions of our<br />
parents or a nursery rhyme. When we were<br />
picking up dining etiquette, we carefully<br />
observed the way others use the utensils.<br />
When we navigate our first day at school<br />
or at the workplace, we are quick to do as<br />
our colleagues do. Imitation is the foundation<br />
of our socialization. But sometimes,<br />
our tendency to replicate others extends<br />
beyond necessary or efficient actions, a<br />
phenomena scientists call overimitation.<br />
Overimitation is a human-specific form<br />
of social learning in which we faithfully<br />
copy irrelevant actions. It is largely responsible<br />
for the ability of our species to<br />
have so many rich cultural traditions and<br />
advanced technology because we are able<br />
to handle more information by accepting<br />
the way that other people behave.<br />
The purpose of a recent Yale study was<br />
to explore whether dogs and dingoes also<br />
display overimitation. There are many<br />
reasons to expect that dogs might follow<br />
human cues. For one, they follow human<br />
gaze and directions, and studies have repeatedly<br />
shown that dogs are prone to look<br />
for a human lead. Surprisingly, the results<br />
revealed that canines do not display this<br />
behavior, suggesting that humans are the<br />
only species to demonstrate this behavior.<br />
The merits of overimitation<br />
One of the most obvious drawbacks of<br />
overimitation is that it can cause a person<br />
to be misled. However, the benefits are<br />
much greater. Consider activities as mundane<br />
as washing your hands or brushing<br />
your teeth. It is important for health reasons<br />
that young children replicate these<br />
behaviors at a young age, regardless of<br />
whether they understand the reasoning<br />
behind the action.<br />
Thinking even further back, consider the<br />
Stone Age. Learning how to start a fire may<br />
have been more likely to persist because<br />
individuals had a tendency to overimitate<br />
the demonstrator. A stick must be spun<br />
quickly for a long time to create a spark. If<br />
the learner did not have the inclination to<br />
continue spinning the stick, despite its apparent<br />
uselessness, then they may not have<br />
been able to start a fire. Without the ability<br />
to start fire, our species would not have<br />
moved on to designing simple machines<br />
and advancing technology.<br />
Overimitation may also be particularly<br />
responsible for the depth and longevity<br />
of human culture. Other species do not<br />
have traditions. Humans maintain rituals<br />
by passing their knowledge on through<br />
generations, although it might not be<br />
necessary or relevant. Consider religious<br />
practices or decorative dressing that have<br />
survived for centuries; without overimitation,<br />
these practices could have been discarded<br />
as ornamental and extraneous.<br />
A drawback of overimitation is that it<br />
can sometimes constrain our exploration.<br />
Overimitation may dampen human trial<br />
18 Yale Scientific Magazine December 2016 www.yalescientific.org
cognitive science<br />
FOCUS<br />
ABOUT THE AUTHOR<br />
ANNA WUJCIAK<br />
ANNA WUJCIAK is a senior Biomedical Engineering Major in Saybrook<br />
College. She works in Jay Humphrey's lab studying cardiovascular<br />
biomechanics and is a member of the Women's Club Water Polo Team.<br />
THE AUTHOR WOULD LIKE TO THANK Laurie Santos, Angie Johnston,<br />
and Paul Holden for their time and passion for their research.<br />
IMAGE COURTESY OF THE DOG BREED INFO CENTER<br />
►Dingoes look very similar to dogs. Yet,<br />
there are stark differences, both physical and<br />
psychological, between the two species of<br />
canines.<br />
FURTHER READING<br />
Smith, B. & Litchfield, C. (2010). Dingoes (Canis dingo) can use human social<br />
cues to locate hidden food. Animal Cognition, 13, 367-376.<br />
and error behavior, while other species are<br />
more inclined to engage in this behavior<br />
because they do not automatically accept<br />
the information others have given them.<br />
Canine independence<br />
At the Canine Cognition Center at Yale,<br />
professor Laurie Santos, PhD candidate<br />
Angie Johnston, and research assistant<br />
Paul Holden explored whether dogs displayed<br />
overimitation. Dingoes were studied<br />
similarly at the Dingo Discovery Center<br />
(DDC) in Australia. Dogs were then<br />
compared to dingoes, a closely related but<br />
non-domesticated species, in an effort to<br />
explore the role of domestication.<br />
In four different trials, animals were<br />
tasked with opening a box to retrieve the<br />
treat inside. These boxes, which Holden<br />
designed at the Yale Center for Engineering<br />
Innovation and Design, were equipped<br />
with a lever on the side and a treat underneath<br />
a flip lid. Although the flip lid was<br />
necessary for getting the treat, the lever<br />
was completely ineffective. At the beginning<br />
of each test, a human completed both<br />
the relevant and irrelevant steps in the<br />
process of opening the box three times<br />
as a display for the animal. The box was<br />
considered solved if the animal was able to<br />
retrieve the treat.<br />
Results showed the dogs and dingoes<br />
filtered out the irrelevant lever action,<br />
even though it was demonstrated to them.<br />
With each of the four tries the test subjects<br />
had with the box, the rate of using the irrelevant<br />
lever decreased and the rate of<br />
solving the box increased. This indicated<br />
that both species of canines were learning<br />
which actions were relevant and which actions<br />
were not based on their own learning<br />
experiences.<br />
Although neither canine species displayed<br />
overimitation, there were differences<br />
in the two species. “Dingoes were<br />
using the lever less than dogs,” Holden<br />
said. “At first glance, dogs and dingoes<br />
look quite similar, but they’re actually very<br />
different.” Dingoes are clever problem<br />
solvers because they are more attentive<br />
and independent, Johnston added. Dogs<br />
have become domesticated over time due<br />
to their companionship with humans, and<br />
therefore they tend to look toward their<br />
human more often when a problem arises.<br />
As dogs have come to rely on humans<br />
more, they may have also become less<br />
adept at independent problem solving,<br />
which might explain why they used the lever<br />
more frequently than dingoes.<br />
A human behavior<br />
The brain mechanism behind overimitation<br />
is not yet well understood. Although<br />
it is outside the scope of Santos’s psychology<br />
lab, other researchers are exploring the<br />
complex brain processes that control decision-making<br />
and overimitation.<br />
Unfortunately, outside of dogs, dingoes,<br />
and chimpanzees, not many species have<br />
been tested for overimitation behavior.<br />
Dogs were selected as a species to study<br />
specifically at Yale because they are highly<br />
social. Chimpanzees have previously been<br />
studied because of their high intelligence<br />
and social tendencies. Scientists assume<br />
that since the closest relative to the human,<br />
the chimpanzee, does not display<br />
this behavior, it is human specific. The absence<br />
of overimitation in chimpanzee behavior<br />
also indicates that humans evolved<br />
this trait sometime within the last seven<br />
million years since our species diverged.<br />
Corvid species, which include birds and<br />
crows, may be valuable to explore next,<br />
as they are also very intelligent creatures.<br />
“Most animals exhibit innate behaviors<br />
that they’ve developed over many years<br />
of evolution,” Johnston said. For example,<br />
think of squirrels who bury nuts every<br />
winter.<br />
If not from overimitation, how do other<br />
species pass on information? Johnston<br />
explained that animals learn through observation,<br />
as opposed to the intentional<br />
instruction method of passing information<br />
like humans. Some information, such<br />
as locomotion, is instinctual. “It’s not that<br />
other animals can’t imitate, it’s just that<br />
they only do it when they need to, whereas<br />
humans tend to do it much more often<br />
than necessary. Animals are better at<br />
prioritizing the information they really<br />
need,” Johnston said. While humans have<br />
complex technology and intricate cultural<br />
practices, other species have more basic<br />
tasks that they can typically address on<br />
their own. Our species is the only one<br />
with a culture that forces us to rely on others.<br />
There are two general hypotheses about<br />
the driver of human overimitation. The<br />
first is that humans can’t help but overimitate.<br />
The second is that humans assume<br />
that the actions they observe are the culturally<br />
appropriate way to behave. “My<br />
thoughts are that it’s really a combination<br />
of both of these hypotheses that cause humans<br />
to overimitate,” Santos said.<br />
Overimitation, for better or worse,<br />
seems to be a distinctly human behavior.<br />
It assists our species to pass on complex<br />
cultural information and maintain a high<br />
degree of advanced technology. It certainly<br />
appears that overimitation is one of the<br />
reasons that humans differ so greatly from<br />
all other species.<br />
www.yalescientific.org<br />
December 2016<br />
Yale Scientific Magazine<br />
19
FOCUS<br />
evolutionary biology<br />
PERPLEXING<br />
FOSSILS &<br />
PECULIAR<br />
FORMS<br />
MAPPING THE TULLY<br />
MONSTER ONTO THE<br />
TREE OF LIFE<br />
by Andrea Ouyang | art by Emma Green<br />
One of the miracles of science is its<br />
ability to extend human memory. As<br />
our computational and technological<br />
capabilities expand, the searchlight of history<br />
broadens our vision into our past and uncovers<br />
new revelations and mysteries alike. Few fields,<br />
then, provide more fascinating applications of<br />
science than the tireless efforts to trace the evolutionary<br />
relationships of creatures, dead and<br />
alive, who populate the tree of life.<br />
Enter Tullimonstrum gregarium.<br />
In the 1950s, Francis Tully discovered a bizarre<br />
fossil in Mazon Creek, Illinois—a site<br />
known for the quality and diversity of creatures<br />
preserved in its deposits, formed 300 million<br />
years ago in the Carboniferous period. For half<br />
a century, no one was quite sure what to make<br />
of the fossil, dubbed the Tully Monster and<br />
declared the state fossil of Illinois in 1989. This<br />
oddly shaped sea creature did not fall under<br />
any neat category, with its pair of cuttlefish-like<br />
fins, long proboscis, and small sharp teeth. Indeed,<br />
paleontologists variously suggested the<br />
organism belonged to animal groups ranging<br />
from wormlike animals to mollusk-like creatures<br />
and even to fish.<br />
A Yale-led research team, led by then graduate<br />
student Victoria McCoy, has at last identified<br />
the Tully Monster. Combining morphological<br />
analysis and close examination of<br />
features resulting from the fossilization process,<br />
the researchers found that the Tully Monster<br />
was most likely a vertebrate with lamprey-like<br />
features. The study, published in April, has put<br />
to rest the mystery of the Tully Monster while<br />
also opening new avenues to further explore<br />
the life of this extraordinary animal.<br />
The exemplary enigma<br />
For a long time, the phylogenetic origins of<br />
the Tully Monster were unknown.<br />
“It’s a classic example of what we generically<br />
call a ‘problematic fossil,’ which is a way of<br />
saying we don’t really know, or didn’t know,<br />
what it was or where it sat in the grand scheme<br />
of things,” said co-author Derek Briggs, a professor<br />
of Geology and Geophysics at Yale and<br />
curator at the Yale Peabody Museum. "There<br />
were a number of these problematic fossils in<br />
older rocks, particularly during the Cambrian<br />
explosion 530 million years ago," Briggs said.<br />
This explosion of life saw the evolution of<br />
animals that would look alien to us today, but<br />
which were actually early offshoots of lineages<br />
leading to modern groups. Subsequently, most<br />
of these peculiar-looking fossils disappeared,<br />
replaced by groups more recognizable to paleontologists<br />
today.<br />
“What we see in the fossil record later on are<br />
generally things that we can identify, or at least<br />
relate to living groups,” Briggs said. “The Tully<br />
Monster was one of those exceptions.” Present<br />
in Carboniferous rocks dating from about 300<br />
million years ago, the Tully Monster was considered<br />
one of the problematica, or fossils that<br />
are difficult to classify. Besides its aquatic environment,<br />
no one really knew anything about it.<br />
Previous solutions to this “problem of the<br />
problematica” included simply classifying the<br />
problematica as phyla that went extinct—in<br />
other words, they were considered a long, divergent<br />
branch of the evolutionary tree of life<br />
that had been cut short, rather than a branch<br />
more closely nested in ancestral animal groups.<br />
Though modern computational approaches to<br />
20 Yale Scientific Magazine December 2016 www.yalescientific.org
evolutionary biology<br />
FOCUS<br />
classification have resolved lingering questions<br />
about many previously problematic fossils, the<br />
Tully Monster had largely resisted phylogenic<br />
placement.<br />
The mission begins<br />
In 2015, McCoy was leading the Briggs lab<br />
group’s annual project, on which all the researchers<br />
in the group were collaborating.<br />
“The Field Museum independently thought<br />
that they would want someone to look at the<br />
Tully Monster, so I independently met with<br />
the Field Museum and curators and collection<br />
managers at the Geological Society of America<br />
meeting,” McCoy said. “We both kind of<br />
simultaneously said we’d like to work on the<br />
Tully Monster.”<br />
The Field Museum, in Illinois, is the closest<br />
major museum to Mazon Creek, where the<br />
majority of Tully Monster fossils have been<br />
unearthed. Its close relationship with local collectors<br />
has helped it acquire a vast collection<br />
of Tully Monster fossils—at over 2,000 specimens,<br />
the largest in the world—which made it<br />
the ideal location to work on the project, according<br />
to Briggs.<br />
It’s elemental, not elementary<br />
Part of what helped the Yale team succeed<br />
where others had failed was meticulous attention<br />
to detail. The fossilization process, though<br />
permitting long-term preservation, can make<br />
morphological features difficult to decipher as<br />
organisms decay and fossilize.<br />
In total, the researchers examined around<br />
1,200 Tullimonstrum specimens, organ by organ,<br />
for general morphological features. As an<br />
example, at the end of the Tully Monster’s proboscis,<br />
the team counted and measured teeth<br />
structures and studied how they were situated<br />
in the Tully Monster’s claw structure. They also<br />
looked at features such as whether the eye bar<br />
sat at the top of the head or went through the<br />
center of the body.<br />
The second component of the research involved<br />
studying features of preservation where<br />
the Tully Monster was discovered. The fossils<br />
were preserved as a discolored film on surrounding<br />
rock where the organism had been<br />
buried, and what appear to be morphological<br />
features sometimes are merely discoloration<br />
from the fossilization process.<br />
This combined analysis of morphological<br />
and preservational features in the Tully Monster<br />
helped McCoy and the team conclude that<br />
the Tully Monster had a notochord, a cartilaginous<br />
skeletal rod and evolutionary precursor<br />
to the spine that classified the fossil as vertebrate.<br />
The researchers had noticed a long line<br />
running down the middle of specimens, previously<br />
identified as the gut of the organism.<br />
While it was entirely possible that the line was<br />
the fossil imprint of either a gut or a notochord,<br />
examining preservation in conjunction with<br />
morphology allowed the researchers to determine<br />
which feature it was.<br />
To further test the vertebrate hypothesis,<br />
the researchers took specimen samples to Argonne<br />
National Laboratory for synchrotron<br />
analysis, a technique that allowed the team to<br />
determine which elements in a sample were<br />
enriched, what differences existed in the elemental<br />
composition of different tissues, and<br />
when they were preserved in the fossil. The<br />
synchrotron data indicated that Tully Monster<br />
eyes were often preserved in pyrite mineral, a<br />
preservational feature shared only by the fish<br />
—the other chordates—at the fossil site. This<br />
was particularly strong evidence that the Tully<br />
Monster was preserved similarly to fish, rather<br />
than other proposed animal groups, such as<br />
worms or mollusks.<br />
The researchers also found that Tully Monster<br />
teeth had a distinct composition from that<br />
of the rest of the bifurcated, claw-like structure<br />
at the end of its proboscis. This discovery also<br />
pointed to chordate affinity, since arthropods,<br />
another previously proposed position for the<br />
Tully Monster, have teeth-like spikes made of<br />
the same material as their claw. Fish teeth, on<br />
the other hand, are biomineralized—minerals<br />
were produced in those tissues to harden them,<br />
making teeth tissue distinct from the rest of the<br />
fish’s mouth.<br />
The teeth were pyritized, or replaced with<br />
iron sulfide, suggesting they were composed<br />
of sulfur-rich material, but not biomineralized,<br />
in contrast to most cartilaginous fishes,<br />
like sharks, whose fossils typically contain<br />
calcium or phosphate compounds. The sulfur-rich<br />
soft tissue was likely made of keratin,<br />
a sulfur-containing protein that is the main<br />
component of fingernails. Interestingly, keratin<br />
is also a component of hagfish and lamprey<br />
teeth, which do not biomineralize, so the<br />
researchers could conclude not only that the<br />
Tully Monster was a chordate, but also that<br />
it preserved similarly to soft-bodied fish like<br />
lampreys and hagfish.<br />
A fossil’s future<br />
Future studies of the Tully Monster include<br />
understanding its ecology and interactions<br />
with its environment and other organisms of<br />
the Carboniferous. It is unknown whether it<br />
was a parasite (like modern lampreys) or a<br />
scavenger, an ambush predator or one that<br />
could sustain periods of continuous swimming.<br />
Its many morphological oddities make<br />
it particularly compelling to study, according<br />
to McCoy.<br />
Luckily for researchers, the Field Museum<br />
recently acquired more Tullimonstrum fossils,<br />
a collector’s gift that could provide researchers<br />
the opportunity to explore and refine<br />
their findings against the new specimens. An<br />
important step, according to Briggs, is to examine<br />
the new collection and see whether it<br />
supports the team’s conclusions. While the<br />
Tully Monster may be long dead and gone,<br />
the story of its existence is sure to fascinate<br />
generations to come.<br />
ABOUT THE AUTHOR<br />
ANDREA OUYANG<br />
ANDREA OUYANG is a sophomore and prospective MCDB major in<br />
Davenport College.<br />
THE AUTHOR WOULD LIKE TO THANK Dr. Victoria McCoy and Professor<br />
Derek Briggs for their time and enthusiasm in speaking about their work.<br />
FURTHER READING<br />
Clements, T. “The Eyes of Tullimonstrum reveal a vertebrate affinity.” Nature<br />
532, 500-503, 2016.<br />
Richardson, E.S. “Wormlike Fossil From the Pennsylvanian of Illinois.”<br />
Science 151 (3706), 75-76, 1966.<br />
www.yalescientific.org<br />
December 2016<br />
Yale Scientific Magazine<br />
21
FOCUS<br />
physics<br />
E X P A N D I N G<br />
the Quantum Computing Toolbox<br />
By Noah Kravitz<br />
Art by Yanna Lee<br />
22 Yale Scientific Magazine December 2016 www.yalescientific.org
physics<br />
FOCUS<br />
In 2011, Canadian tech company<br />
D-Wave stunned the world by announcing<br />
that it would market a<br />
functioning quantum computer. Soon,<br />
companies ranging from Google to NASA<br />
bought versions of the device, and scientists<br />
began scrambling to evaluate what<br />
potentially was the biggest technological<br />
breakthrough of the century. One<br />
third-party test, in which the new quantum<br />
computer solved a complex math<br />
problem 3,600 times faster than a cutting-edge<br />
IBM supercomputer, seemed<br />
to substantiate D-Wave’s claims of quantum<br />
computation. Other tests found<br />
no evidence of quantum activity at all.<br />
Quantum computing, an idea which has<br />
captivated physicists and computer scientists<br />
alike since its conception in the 1980s,<br />
has proven difficult to realize in practice.<br />
Because quantum computers rely on the<br />
uncertainty built into the laws of quantum<br />
physics, they are extremely sensitive to<br />
their environments. A small imperfection<br />
in even a single component of the design<br />
can be devastating. One technical challenge<br />
is that heat energy can disrupt the<br />
fragile quantum states, so quantum technology<br />
is usually cooled almost to absolute<br />
zero (-273 degrees Celsius). D-Wave’s<br />
quantum computer is small enough to<br />
hold in the palm of your hand but has to<br />
be housed in a 10-foot-tall refrigerator.<br />
Yale researchers, led by Professor of<br />
Electrical Engineering and Physics Hong<br />
Tang, have developed a new version of a<br />
device called a piezo-optomechanical resonator<br />
that could allow quantum computers<br />
to operate at higher temperatures. The<br />
paper, which is co-authored by graduate<br />
students Xu Han and Chang-Ling Zou, describes<br />
an improved method of connecting<br />
information in physical and electrical<br />
domains. This advance could be used as<br />
the basis for reliable memory storage for<br />
quantum computers—an important step<br />
towards stronger quantum computing.<br />
From Schrodinger’s cat to national<br />
security<br />
Quantum computing fundamentally<br />
differs from classical computing in that<br />
it relies on the non-intuitive quantum<br />
properties of light and matter. In familiar<br />
classical computation, information is<br />
stored as bits which can take on the values<br />
0 and 1—they are simple on/off electrical<br />
switches, and it is easy to check their<br />
positions. The computer then performs<br />
tasks using sequences of logical operations<br />
on the bits. For example, it might<br />
say that if bit A is 0, then bit B should<br />
be set to 0, but if bit A is 1, then bit B<br />
should be set to 1; or that bit C should be<br />
set to 1 only if bits A and B are different.<br />
In quantum computing, by contrast, the<br />
situation is not so straightforward. First of<br />
all, information is stored in qubits (short<br />
for “quantum bits”) which have more than<br />
two possible values: 0, 1, and a combination<br />
of 0 and 1. These qubits are particles<br />
with distinct measurable quantum states<br />
corresponding to “0” and “1,” but one of<br />
the principles of quantum physics is that<br />
sometimes we can predict the result of<br />
a measurement only in terms of probabilities.<br />
So in quantum mechanics, even<br />
though sometimes we might know that<br />
we will always measure the particle as “0,”<br />
there can also exist a scenario in which<br />
there is a 50 percent chance of finding the<br />
particle in the “0” state and a 50 percent<br />
chance of finding it in the “1” state. The<br />
surprising part is that, mathematically<br />
speaking, the latter particle is actually in<br />
both states equally until we measure it as<br />
being in one or the other, and it is meaningful<br />
to think of such a qubit as having<br />
value ½ representing a “mixed” state even<br />
though ½ is not a possible measurement.<br />
Another useful property of quantum<br />
mechanics called entanglement links the<br />
measurements of different particles. For<br />
example, if particles A and B are entangled,<br />
then we might know that whenever<br />
we measure both particles, we will get one<br />
“0” and one “1.” In this case, measuring<br />
one qubit immediately determines the<br />
value of the other, and it is possible to use<br />
this property to “teleport” information!<br />
The unique logical underpinnings of<br />
quantum computation allow quantum<br />
computer to approach old problems in<br />
new ways. Since qubits are more complex<br />
than regular bits, quantum algorithms are<br />
often more streamlined than their classical<br />
counterparts, especially when searching<br />
for optimal solutions to problems. For<br />
example, if we want to find a car that is<br />
hidden behind one door out of a million, a<br />
classical computer would have to check the<br />
doors one by one, and, in the worst-case<br />
scenario, it would have to make a million<br />
queries. A quantum computer, by contrast,<br />
can use a probabilistic algorithm to find<br />
the car in at most only a thousand queries.<br />
Quantum computation has potential applications<br />
in many problems that would<br />
take classical computers longer than the<br />
age of the Earth. In the best-known example<br />
of this principle of “quantum speedup,”<br />
computer scientists have created a quantum<br />
algorithm that can factor large numbers<br />
(essentially a needle-in-a-haystack<br />
problem like the car example above) exponentially<br />
faster than is possible for any<br />
classical algorithm. Although this problem<br />
may not seem very exciting, it in fact underlies<br />
many more complex processes such<br />
as cryptography. Similar principles apply<br />
to choosing cost-effective combinations of<br />
building materials and even to identifying<br />
keywords for news articles. Unsurprisingly,<br />
quantum computation is often the best<br />
way to model complex natural systems.<br />
We have made significant progress over<br />
the past few decades towards meeting the<br />
challenges of quantum computing. As early<br />
as the mid-1990s, we have manipulated<br />
qubits and written codes to correct spontaneous<br />
errors in quantum computers. In<br />
the 2000s, we demonstrated long-distance<br />
entanglement. In 2013, Hong Tang and his<br />
team contributed to the corpus of knowledge<br />
when they determined a method<br />
for measuring quantum systems without<br />
permanently altering them. Now, in 2016,<br />
the Tang Lab at Yale has once again expanded<br />
the quantum computing toolbox,<br />
this time in the stubbornly challenging<br />
field of information storage and transfer.<br />
A new approach to quantum memory<br />
You probably carry around in your<br />
pocket a crucial piece of the new Yale<br />
device: Smartphones contain the materials<br />
that Tang and his team used to bridge<br />
the mechanical-electrical gap. Piezoelectrics<br />
are materials, usually crystals, that<br />
accumulate charge when compressed,<br />
twisted or bent. For instance, when<br />
a piezoelectric sheet is creased, a net<br />
negative charge forms at the fold, and<br />
net positive charges form at the ends.<br />
Conversely, when an external magnetic<br />
field causes charges in a piezoelectric to<br />
www.yalescientific.org<br />
December 2016<br />
Yale Scientific Magazine<br />
23
FOCUS<br />
physics<br />
IMAGE COURTESY OF HONG TANG<br />
►Professor Hong Tang (right), along with graduate students Chang-Ling Zou (left) and Xu Han<br />
(not pictured), developed a piezo-optomechanical resonator that has applications to quantum<br />
memory storage.<br />
move, the object responds by changing<br />
shape physically. In this way, vibrations<br />
in physical objects and electrical fields<br />
can easily be connected, or, as physicists<br />
say, coupled. Piezoelectrics in smartphones<br />
often power tiny speakers— they<br />
convert electrical signals into sound<br />
waves, which arise from physical pulses.<br />
The Yale piezo-optomechanical device<br />
consists of a pair of tiny resonators:<br />
a silicon wafer and a wire loop situated<br />
above it. “It is useful to think of a resonator<br />
like a tuning fork because it responds<br />
most powerfully to a particular resonant<br />
frequency,” said Han, an electrical engineering<br />
Ph.D candidate who worked on<br />
the project. The two ends of the wire<br />
loop do not quite connect, so electrical<br />
charges tend to bounce back and forth<br />
around the circle, which functions as an<br />
electrical resonator in the microwave region<br />
of the electromagnetic spectrum.<br />
The wafer, which is about as thick as five<br />
sheets of paper, functions as an acoustic,<br />
or mechanical, resonator. This resonator<br />
is coated with a thin layer of aluminum<br />
nitride, a piezoelectric material,<br />
which facilitates the exchange of oscillations—and<br />
energy— between mechanical<br />
and electrical components. “If you<br />
want to transfer information between<br />
two systems, it is necessary to have an<br />
efficient coupling mechanism,” Han said.<br />
The idea of coupling between mechanical<br />
and microwave electrical domains<br />
is not new; the Yale team’s innovation<br />
is achieving stronger coupling on a<br />
smaller scale. The key is using resonators<br />
with a higher frequency: Whereas<br />
other designs have used frequencies on<br />
the order of a few million oscillations<br />
per second, the Yale design runs at ten<br />
billion oscillations per second. As a result,<br />
the device is solidly in the so-called<br />
strong-coupling regime —meaning that<br />
the rate of information transfer is greater<br />
than the natural energy dissipation<br />
rates of the individual systems—and<br />
transmitted signals are clearer and longer-lasting.<br />
Yet high frequency comes at<br />
the cost of increased construction difficulties.<br />
“Since the device is small, it<br />
is more susceptible to perturbations in<br />
the environment,” Tang said. As a result,<br />
the design carefully balances considerations<br />
of compactness and robustness.<br />
The researchers believe that applications<br />
of their breakthrough lie mostly in the far<br />
future. “This is fundamental research, so<br />
it’s not immediately pertinent to daily life,”<br />
Han said. Instead, the piezo-optomechanical<br />
resonator’s real value is as a component<br />
of more complex systems. Because of the<br />
strong coupling achieved, it is well suited<br />
for quantum uses where “noise” from ambient<br />
heat (analogous to TV static) would<br />
otherwise be disruptive. “For high-frequency<br />
devices, the temperature requirement is<br />
not as low,” Han said. Chang-Ling Zou, a<br />
postdoctoral student in Tang’s lab, hopes to<br />
develop this strength into a basis for quantum<br />
memory storage, which is currently<br />
unfeasible at most temperatures. Small<br />
vibrating crystals would serve as physical<br />
memory, and the resonators would convert<br />
between these crystals and the computational<br />
part of the computer, which would<br />
likely operate in the microwave domain.<br />
The Yale team is also looking to incorporate<br />
visible light into their design. “The<br />
next step is integrating an optical resonator<br />
and using the acoustic resonator<br />
as an intermediary between microwave<br />
and optics,” Han said. Accomplishing<br />
this feat could improve computer signal<br />
processing, radio receiving efficiency,<br />
and information transmission across<br />
long distances via optical fiber cables.<br />
Given its versatility, the piezo-optomechanical<br />
resonator may find its way into<br />
all kinds of applications. From analyzing<br />
the stock market to sending trans-Atlantic<br />
messages, you can expect to hear more about<br />
this small device in big-time situations.<br />
ABOUT THE AUTHOR<br />
NOAH KRAVITZ<br />
NOAH KRAVITZ is a freshman in Calhoun College. He is interested in<br />
studying math, music, physics and philosophy.<br />
THE AUTHOR WOULD LIKE TO THANK Xu Han, Chang-Ling Zou, and<br />
Professor Hong Tang for explaining their research.<br />
FURTHER READING<br />
Li, Mo, W.H.P. Pernice, and H.X. Tang. “Ultrahigh-Frequency Nano-<br />
Optomechanical Resonators in Slot Waveguide Ring Cavities.” Applied<br />
Physics Letters 07 (2010).<br />
24 Yale Scientific Magazine December 2016 www.yalescientific.org
evolutionary biology<br />
FEATURE<br />
A WORLD OF WONDER<br />
Opening the David Friend Hall at the Peabody Museum<br />
►BY CHUNYANG DING<br />
Nearly every observed galaxy has a giant black hole at<br />
its center. Step into the Peabody’s new David Friend Hall<br />
and it might take a minute for your eyes to adjust to the<br />
darkness—and then another hour for your mind to adjust<br />
to the dazzling marvels that surround you. From the<br />
2000-pound, single-quartz crystal from Namibia to the<br />
30-million-year-old sandstone concretion with smooth<br />
undulating curves, each object in the hall aims to wows<br />
visitors. Curators carefully chose every detail—from the<br />
lighting to the case design—to showcase the world-class<br />
treasures here in New Haven, Connecticut.<br />
Dramatic lighting highlights specimens with dazzling<br />
clarity and draws attention to the kaleidoscope of colors<br />
filling the hall. This focus on showmanship was well<br />
developed; David Friend (YC ’69), who donated three<br />
million dollars for the exhibit, hoped to fill people with<br />
a sense of wonder. “The function of a museum is not so<br />
much to teach but to inspire a desire to learn,” Friend<br />
said shortly before he cut the ribbon to officially open<br />
the exhibit.<br />
It is fitting for Yale to host this transformative mineral<br />
exhibit, since modern mineralogy originated here. Just<br />
as Carl Linneaus brought order to the natural world<br />
by classifying plants and animals, Yale professor James<br />
Dwight Dana brought order to the world of rocks and<br />
minerals with a classification scheme that is still used<br />
today. Geology has always been strong at Yale; Benjamin<br />
Silliman, Yale’s first science professor, started the<br />
American Journal of Science in 1818. Not only is the AJS<br />
IMAGE COURTESY OF MICHAEL MARSLAND<br />
►Prominent members of the Yale and New Haven communities<br />
attended the ribbon cutting ceremony with David Friend (YC<br />
’69). The opening speeches set the tone for an exhibit that<br />
would wow visitors.<br />
the oldest scientific journal in the United States, it is one<br />
of the most influential journals in the fields of geology<br />
and mineralogy.<br />
The Peabody Museum continues to challenge the<br />
expectations for natural history museums with the David<br />
Friend Hall. Rather than bombard visitors with text, the<br />
exhibit isolates the singular beauty of sparkling minerals.<br />
Educational materials for the displays are captured by a<br />
smartphone application, where visitors can access and<br />
browse background information. In addition, the gallery<br />
will feature rotating exhibits: many gems are on loan from<br />
private collectors, so new treasures can be featured in the<br />
future. Although art galleries often feature loaned art,<br />
the David Friend Hall is one of the first natural history<br />
exhibits to do the same.<br />
And the treasures are dazzling, indeed. Beside the<br />
2000-pound quartz stands a giant geode from Uruguay,<br />
completely encrusted by deep purple amethyst shards.<br />
Nearby, a white-board-sized fossil of a fan-like frond<br />
flanked by ancient fish demands your attention. The<br />
crystals, ranging from a five-by-four-foot fluorite from<br />
China to miniature “thumbnail” specimens in a display<br />
case, vary in size, shape, and geographic origin. “If<br />
you go around and look at every single crystal, they’re<br />
from all over the world,” said Dave Skelly, the Director<br />
of the Peabody Museum. Stefan Nicolescu, head of the<br />
Peabody’s minerology collections, guided the selection<br />
of minerals, consulting private collections throughout<br />
the region and selecting specimens for their wow factor.<br />
“The interest is to stir curiosity and to make people want<br />
to know more about these things,” said Nicolescu.<br />
The recent ribbon cutting ceremony thoroughly<br />
explored this theme of curiosity and inspiration: “The<br />
goal is to capture people’s imagination, particularly the<br />
imaginations of budding young scientists, to get them<br />
fascinated by the natural world,” said Jay Ague, chair of<br />
Yale’s Geology and Geophysics department. They hope<br />
to reach far beyond New Haven. Since its conception<br />
150 years ago, the Peabody Museum has served as the<br />
archetype for many natural history museums. The<br />
curators of the David Friend Hall hope that their setup<br />
will also set an example that diffuses globally.<br />
For New Haven residents and Yale University students,<br />
the hall breathes new life into an already brilliant<br />
collection of natural history. “I think this exhibit will<br />
certainly bring more students up [to the Peabody],”<br />
said Dean Jonathan Holloway. The brilliant jewels may<br />
prompt curiosity for understanding our world.<br />
www.yalescientific.org<br />
December 2016<br />
Yale Scientific Magazine<br />
25
FEATURE<br />
human evolution<br />
THE EXISTENTIAL CRISIS OF THE<br />
FEMALE ORGASM<br />
►BY KRISSTEL GOMEZ<br />
The female orgasm has always provoked biologist’s curiosity.<br />
From an evolutionary perspective, the male orgasm has a<br />
clear purpose: it is required for ejaculation and the subsequent<br />
transfer of sperm. Explaining the female orgasm is more difficult,<br />
since fertilization and reproduction will occur whether<br />
or not a female orgasm occurs. In fact, female orgasms occur<br />
more frequently during masturbation or homosexual intercourse<br />
than during heterosexual intercourse. Natural selection,<br />
the driving process of evolution, favors traits that yield a<br />
survival or reproductive advantage to a species, so why has the<br />
female orgasm evolved if it provides no apparent survival or<br />
reproductive advantage?<br />
Yale’s Günter Wagner and his colleague, Mihaela Pavlicev,<br />
recently identified that the female orgasm—like the male orgasm—predates<br />
the primate lineage. Thus, the human female<br />
orgasm likely evolved from an older, functional trait and was<br />
passed down through generations. Here, we will explore the<br />
history of this trait and how its function has changed since it<br />
originated.<br />
For species whose ovulation is induced by copulation, it is<br />
thought that orgasms stimulate the release of hormones such<br />
us prolactin and oxytocin, triggering ovulation. In contrast,<br />
women are spontaneous ovulators. Although they too release<br />
prolactin and oxytocin during orgasm, their ovulation cycles<br />
do not depend on these hormones.<br />
Differences in ovulation cycles between species may have<br />
evolved in tandem with anatomical differences. Wagner’s<br />
study predicted that for spontaneously ovulating animals, the<br />
distance between the clitoris and the vaginal opening can be<br />
larger than for animals with copulation-induced ovulation,<br />
whose clitorises should be within (or near) their vaginal openings.<br />
In accordance with this prediction, external, non-penile<br />
stimulation of the clitoris is required for many women to<br />
achieve orgasm, because the clitoris is relatively far from the<br />
vaginal canal.<br />
Looking deeper into anatomical evolution, Wagner and his<br />
colleague studied databases of veterinary literature comparing<br />
female animal anatomy. In spite of a dearth of accurate studies<br />
on female genitalia, they found enough data to support<br />
their hypothesis. They discovered that in most species of reptiles,<br />
birds, and mammals, a single canal is used for urination<br />
and copulation. In these animals, the clitoris is often within or<br />
nearby the copulatory canal. However, in the ancestors of humans<br />
and other primates, the urogenital canal–the canal used<br />
for urination and copulation–shortened until the urethra became<br />
an entirely independent canal. As these two canals separated,<br />
the distance between the copulatory canal and the clitoris<br />
also increased.<br />
Wagner realized copulation-induced ovulation occurred<br />
most often in animals in which the clitoris was located within<br />
or near the copulatory canal. Spontaneous ovulators, in contrast,<br />
evolved to separate the clitoris and vagina. Together,<br />
this information suggests that the common ancestor of many<br />
mammals was a copulation-induced ovulator. However, as<br />
spontaneous ovulation evolved in humans and primates, clitoral<br />
stimulation as a means to induce ovulation became useless,<br />
and evolution distanced the clitoris from the copulatory canal.<br />
Though researchers have yet to prove that copulation-induced<br />
ovulation is triggered by clitoral stimulation and orgasm,<br />
the theory is pharmacologically testable. Future studies<br />
could use drug-induced anorgasmia–the inability to achieve<br />
orgasm–and the subsequent monitoring of an animal’s ovulation<br />
cycle, to begin to answer this question.<br />
In the context of spontaneous ovulation, clitoral stimulation<br />
leading to female orgasm may serve another purpose. For example,<br />
orgasm might improve pair bonding. Wagner emphasized<br />
that, although the female orgasm may not make a clear<br />
contribution to reproductive fitness, this does not reflect its<br />
modern importance. “Maybe the way to think about the female<br />
orgasm is as a type of art . . . which doesn’t have to have<br />
a specific purpose but still has value,” Wagner explained, referencing<br />
the way we value our ability to admire art despite its<br />
non-existent connection with reproduction or fitness.<br />
Wagner’s research has powerful and liberating implications<br />
for both men and women, freeing them from preconceived<br />
notions about the meaning of female orgasm during heterosexual<br />
intercourse. The research will hopefully discourage unhealthy<br />
notions, such as Sigmund Freud’s labeling of the clitoral<br />
orgasm as “infantile,” or theories that claim the female<br />
orgasm occurs more frequently with higher-quality males as<br />
a mechanism for retaining larger quantities of their sperm.<br />
Wagner and Pavlicev explain the difficulties associated with<br />
achieving female orgasm during heterosexual intercourse as<br />
an effect of evolution without any intrinsic implications regarding<br />
the male’s value.<br />
IMAGE COURTESY OF WIKIMEDIA COMMONS<br />
►The female orgasm releases the hormones prolactin and<br />
oxytocin, which are theorized to trigger ovulation and fertilization.<br />
26 Yale Scientific Magazine December 2016 www.yalescientific.org
materials science<br />
FEATURE<br />
PLASTIC PREYS ON DEEP-SEA<br />
ORGANISMS<br />
►BY DIANE RAFIZADEH<br />
IMAGE COURTESY OF WIKMEDIA COMMONS<br />
►Marine debris, the result of human plastic waste, on the<br />
beaches of Dar es Salaam, Tanzania. These large plastic<br />
pieces are shredded by weathering into more dangerous, easily<br />
ingestible microplastics.<br />
The dangers of oceanic plastic pollution are well known:<br />
throughout social media, trending videos portray turtles<br />
trapped in plastic netting and decomposed birds with<br />
plastic in their stomachs. The reality of plastic pollution is<br />
heart-wrenching, and researchers are continuously producing<br />
more evidence to demonstrate the extent of the problem.<br />
Discoveries from the past 20 years have revealed that organisms<br />
living in shallow waters and the middle layers of<br />
the ocean ingest copious amounts of plastic. Most recently,<br />
however, researchers at the University of Oxford discovered<br />
that deep-sea organisms—rarely studied in this context until<br />
now—are also consuming plastic at alarming rates. Their<br />
finding is particularly concerning because it demonstrates<br />
the vast impact of human plastic pollution: our trash has<br />
reached one of the Earth’s most remote and fragile environments.<br />
Conducted primarily by Michelle Taylor and Lucy Woodall<br />
at Oxford, the research concentrates on microfibers, the<br />
most common type of microplastic found in the environment.<br />
Microplastics are small plastic pieces, usually less than<br />
five millimeters in diameter (the width of a thumbtack), that<br />
are created when larger plastic debris is weathered and broken<br />
apart, while microfibers are a sub-class of fiber-shaped<br />
microplastics that often come from fibers on clothing. They<br />
are particularly dangerous for aquatic wildlife because they<br />
can easily get trapped in an animal’s digestive track or gills,<br />
lessening its feeding ability, damaging its digestive track, and<br />
often leading to its starvation. Organisms also face contamination<br />
by concentrated organic pollutants and metals that<br />
are harbored by the plastics.<br />
Taylor and Woodall’s research was inspired by earlier findings<br />
that discovered microplastics in deep-ocean sediments.<br />
“We were discussing what deep-sea animals eat, which is<br />
mostly particle matter falling from shallower waters—something<br />
called marine snow, and if this snow would have microplastics<br />
in it,” said Taylor, a senior postdoc at Oxford.<br />
The researchers explored deep-sea organisms in the equatorial<br />
mid-Atlantic and southwest Indian Ocean by sending<br />
a robot to the seafloor to scoop up organism samples. Reaching<br />
such depths was a major challenge, but the research team<br />
had access to a UK research ship and the Remote Operated<br />
Vehicle Isis robot, which can reach depths of 6000 meters.<br />
From their collected samples, they studied three distinct<br />
phyla: Cnidaria (such as jellyfish and corals), Echinodermata<br />
(such as starfish and sea cucumbers), and Arthropoda (such<br />
as crustaceans). The researchers recorded the depth where<br />
each organism was found, the type of microplastic it had interacted<br />
with, and the microplastic’s location on or within<br />
the organism. Most of the studied organisms, such as squat<br />
lobsters, corals, and sea cucumbers, contained microplastics<br />
in their oral areas, stomachs, and gills, indicating that<br />
the plastics were either ingested or inhaled. For example, the<br />
researchers found microplastics made of polypropylene, a<br />
polymer that can carry compounds such as DDE, a pesticide.<br />
The logical follow-up question is what we can do about human<br />
plastic pollution, but the answer is difficult because of<br />
the sheer prevalence of plastics in daily life. “It’s surprising<br />
how much clothing we wear is made up entirely of acrylic or<br />
polyester—I challenge you to check yours now,” said Taylor.<br />
Scientists are currently designing safer plastics. Paul Anastas,<br />
the Director of Yale’s Center for Green Chemistry and<br />
Green Engineering, says research should focus on developing<br />
biodegradable plastics that do not persist in the environment.<br />
“There is a worldwide network of people producing<br />
these solutions, and they need to be implemented much<br />
more rapidly.” The twelve principles of green chemistry include<br />
designing safer chemicals, using safer solvents, and reducing<br />
energy use.<br />
Governments, too, are taking measures to reduce the<br />
amount of plastic waste released into marine environments.<br />
In December of 2015, President Obama signed the Microbead-Free<br />
Waters Act, banning the cosmetics industry from using<br />
plastic microbeads, such as the exfoliating beads in facial<br />
soaps that are washed down the drain and released into the<br />
ocean.<br />
The public also has a responsibility to keep plastics out of<br />
our oceans. We can trash the “throw-away” mentality that<br />
leads us to use disposable plastic cups and utensils and opt<br />
for reusable options like cloth bags at the grocery store. In the<br />
meantime, Taylor hopes to see further research that probes<br />
deep-sea plastic pollution.<br />
www.yalescientific.org<br />
December 2016<br />
Yale Scientific Magazine<br />
27
FEATURE<br />
medicine<br />
insight into<br />
EYESIGHT<br />
REAWAKENING RETINAL STEM CELLS<br />
by CHRISTINE XU<br />
art by YANNA LEE<br />
28 Yale Scientific Magazine December 2016 www.yalescientific.org
A<br />
lizard escaping from a predator can lose its tail as a defense<br />
mechanism—while the detached tail writhes on the ground<br />
and confuses the predator, the lizard scurries away. During<br />
the following months, the lizard grows back a new tail. How does<br />
this regeneration occur? The answer lies in the behavior of stem<br />
cells, specialized cells that can both renew themselves and generate<br />
various other cell types.<br />
Humans have stem cells, too, although they behave differently<br />
from those in the lizard’s tail. Many distinct populations of stem<br />
cells reside within each of us. Neural stem cells in our brains, for<br />
instance, can become new neurons or glial cells. Blood stem cells<br />
in our bone marrow can turn into new white blood cells, red blood<br />
cells, or platelets coursing through our bloodstream. Since stem cells<br />
are extremely versatile and can generate a number of new cell types,<br />
a recent goal of researchers and clinicians has been to harness their<br />
regenerative abilities for replacement therapies—restoring lost organs<br />
and tissues in human patients.<br />
Bo Chen, associate professor of Ophthalmology at Yale, studies<br />
human retinal stem cells. Recently, his team figured out how to<br />
reawaken the stem cell ability of a special group of dormant cells,<br />
called Muller glial cells (MGs). MGs are found in the retina, a tissue<br />
at the back of the eye that detects visual information in the form of<br />
light. While MGs in humans are not true stem cells, they can behave<br />
like stem cells under certain circumstances, such as extreme injury.<br />
MGs are normally asleep, in an inactive state, but injury can reawaken<br />
them and cause them to reenter the cell cycle and develop regenerative<br />
stem cell abilities. Chen and his research team discovered<br />
how to wake up MGs and cause them to proliferate without injuring<br />
them, a strategy that could potentially help to restore retinal cells<br />
damaged by disease.<br />
In invertebrates, such as zebrafish, MGs are permanently active<br />
retinal stem cells capable of regenerating damaged and lost cells. In<br />
mammals, however, MGs typically remain dormant and incapable<br />
of spontaneously re-entering the cell cycle without outside intervention.<br />
While past studies have shown that severe retinal injuries<br />
can stimulate MG proliferation and stem cell activation, Chen found<br />
that injuring MGs was counterproductive to the goal of regeneration.<br />
“We wanted to do something different: activating these cells<br />
without inflicting any damage to the retina. Our goal was to make<br />
neurons without having to kill any neurons in the first place,” Chen<br />
said.<br />
The cell’s decision to remain dormant or become active depends<br />
on a network of signaling pathways that is poorly understood.<br />
Chen’s team suspected that the Wnt signaling pathway was involved,<br />
since this pathway is also involved in embryonic development and<br />
the regulation of stem cell behavior. Thus, the researchers decided<br />
to test if they could reawaken MGs by increasing the activity of the<br />
Wnt pathway.<br />
In the traditional signaling pathway, Wnt proteins bind to cell receptors<br />
to initiate a cascade that eventually results in inhibition of<br />
the GSK3 protein. GSK3 normally degrades β-catenin, a signaling<br />
molecule that causes a number of cellular effects. Therefore, when<br />
the Wnt signaling pathway is activated, GSK3 is inactivated and<br />
β-catenin accumulates inside the cell. The increase in β-catenin then<br />
turns on a set of genes that can change the activity of the cell by<br />
promoting proliferation. To study how Wnt signaling affects MGs,<br />
Chen’s team used viruses to transfer the β-catenin gene into mouse<br />
MG cells, thus mimicking the effects of an activated Wnt pathway.<br />
medicine<br />
FEATURE<br />
After the team transferred the β-catenin gene into the cells, a<br />
significant number of MGs began to reenter the cell cycle and proliferate.<br />
To confirm the role of β-catenin, the researchers next deleted<br />
the GSK3 gene, which encodes for the protein that degrades<br />
β-catenin—again causing a buildup of β-catenin. Once again, they<br />
observed significantly increased proliferation of MGs. They also<br />
discovered that β-catenin directly affected the expression of a gene<br />
called Lin28, which has been shown to regulate stem cell decisions.<br />
Chen’s team had made a remarkable discovery, being the first<br />
to activate the proliferative response of MGs without retinal injury.<br />
Now that they were capable of waking up MGs, they wanted to<br />
know whether their reactivated MGs were behaving like true stem<br />
cells—that is, whether the MGs were capable of generating other<br />
cell types. They transferred the β-catenin gene to a population of<br />
MGs and gave them time to activate and differentiate. When they<br />
analyzed the gene expression of the MGs, they found that the reactivated<br />
MGs expressed similar genetic profiles to several retinal cell<br />
types, suggesting that the MGs were able to differentiate in a stemcell-like<br />
manner.<br />
The impact of Chen’s study lies in its implications for stem cell<br />
regenerative therapy. “Stem cell therapies are promising for treating<br />
diseases of the human retina, where there is a loss of retinal cells,”<br />
Chen explained. These diseases include macular degeneration and<br />
glaucoma, both of which cause vision problems and can eventually<br />
lead to blindness. If stem cells could be used to regenerate lost retinal<br />
cells, then scientists and clinicians would have a novel tool to<br />
treat these types of degenerative retinal diseases. “We can activate<br />
this group of MG cells and potentially direct their differentiation<br />
into any type of retinal neurons, which could replace lost cells. Essentially,<br />
we are asking our retinas to repair themselves,” Chen said.<br />
Although the preliminary results are promising, Chen and the<br />
other scientists still do not fully understand the complex process of<br />
MGs differentiation. For instance, the researchers still do not know<br />
how reactivated MGs choose to become one cell type or another.<br />
“The challenge now is that even when the MGs reenter the cell cycle,<br />
they might not make the exact type of neuron we want,” Chen<br />
said. He would like to better understand the signaling pathways that<br />
guide MG differentiation in order to produce the cell types required<br />
for regenerative therapy. In the future, Chen would like to test different<br />
sets of factors that control MG differentiation. “We hope to use<br />
these factors to guide the differentiation of the reactivated MGs to<br />
make the types of cells that we want.”<br />
Chen and his team are currently focusing on two types of neurons:<br />
photoreceptor cells and ganglion cells. Both cell types are extremely<br />
important in eyesight, detecting light from the environment and<br />
converting it into electrical signals that can be routed to the brain.<br />
If scientists such as Chen’s team successfully produce new photoreceptor<br />
cells and ganglion cells from MGs, then these cell types could<br />
be restored in patients who have lost them due to injury or disease.<br />
Retinal stem cells are an important research topic, and Chen’s findings<br />
will be extremely valuable for other researchers in the field. For<br />
the first time, retinal cells regained stem cell abilities without injury.<br />
As the discovery improves our understanding of the fundamental<br />
signaling pathways behind stem cell differentiation, researchers<br />
could soon harness the abilities of stem cells to heal damaged tissues<br />
in patients. Chen is optimistic that other scientists will continue to<br />
build upon his findings. “This type of research will ultimately greatly<br />
benefit patients if we are successful,” he predicted.<br />
www.yalescientific.org<br />
December 2016<br />
Yale Scientific Magazine<br />
29
SUPERBUGS<br />
SEE<br />
STARS<br />
by Grace Niewijk || art by Anusha Bishop<br />
“We talk about a pre-antibiotic era and an antibiotic era. If we’re not careful, we will soon be in a post-antibiotic era.<br />
And, in fact, for some patients and some microbes, we are already there.”<br />
- Tom Frieden, CDC Director<br />
Scientists predict that, without a major pharmacological breakthrough,<br />
deaths from antibiotic-resistant bacteria will surpass<br />
cancer deaths by the year 2050. However, thanks to a team from<br />
the Melbourne School of Engineering, that breakthrough may be a bit<br />
closer. The team designed tiny, star-shaped polymers that were highly<br />
effective against multiple types of bacteria without allowing resistance<br />
development. Though more testing and development is required, scientists<br />
are hopeful that these polymers could avert a deadly global<br />
health crisis.<br />
Just as humans can build up tolerance to poisons by exposing themselves<br />
to incremental, sub-lethal doses over time, bacterial colonies<br />
can develop resistance to antibiotic drugs when exposed to non-lethal<br />
quantities. Although the biological processes are different, the result is<br />
the same: substances that would normally prove lethal suddenly fail to<br />
have an effect. In the case of antibiotic-resistant bacteria, this can mean<br />
infections and diseases that were once easily treated suddenly become<br />
deadly. Without antibiotics, even routine procedures like kidney dialysis,<br />
appendectomies, hip replacements, and biopsies would suddenly<br />
carry extremely high risk.<br />
Manisha Juthani-Mehta, an infectious diseases physician at the<br />
Yale School of Medicine, notes that drug-resistant bacteria have been<br />
around for decades, but modern medicine is exacerbating their proliferation.<br />
“We have far more [drug-resistant bacteria] now with prevalent<br />
overuse of antibiotics,” she said. The agricultural industry is by far<br />
the largest culprit of overuse, purchasing 80 percent of all antibiotics<br />
sold in the United States every year. The drugs help promote plant and<br />
livestock growth and protect crops and animals from diseases. While<br />
these uses are important, they are not so crucial that cutting back<br />
would be impossible. Overuse drastically increases the rate at which<br />
drug-resistant bacteria develop and spread in the environment and in<br />
30 Yale Scientific Magazine December 2016 www.yalescientific.org
iomedical engineering<br />
FEATURE<br />
the food supply. Nursing homes and hospitals are other major breeding<br />
grounds for antibiotic-resistant bacteria. “In nursing homes, infections<br />
are commonly suspected and antibiotics are frequently prescribed.<br />
Older nursing home residents have multiple medical problems and are<br />
often exposed to multiple rounds of antibiotics” said Juthani, whose<br />
expertise involves infections in older adults. Although scientists and<br />
government agencies have encouraged farmers and medical professionals<br />
to limit antibiotic use, no strict regulations have been passed.<br />
For some infections, we are running out of treatment options. “We<br />
are more often stuck using very toxic, old antibiotics because we have<br />
no choice,” said Juthani. In some cases, even these last resorts are failing.<br />
Each time a bacterial infection becomes resistant to a particular<br />
drug, physicians can only hope that a new, more effective drug will<br />
be developed. Unfortunately, because bacteria generally develop resistance<br />
to a drug very quickly and thereby render it obsolete, antibiotic<br />
development is not profitable for pharmaceutical companies. “There<br />
have only been one or two new antibiotics developed in the last 30<br />
years,” said Greg Qiao from the University of Melbourne in a Science<br />
Daily article.<br />
That’s where the real stars come in. A team of Australian scientists—<br />
including Qiao, Eric Reynolds, and PhD candidate Shu Lam—recently<br />
published a paper in Nature Microbiology describing a promising alternative<br />
technology to combat multidrug-resistant bacteria. Instead<br />
of designing a traditional chemical drug treatment, the team developed<br />
what they call “structurally nanoengineered antimicrobial peptide<br />
polymers,” or SNAPPs, for short. The researchers were inspired<br />
by natural antimicrobial peptides, which are small proteins that play<br />
important roles in the immune systems of many organisms. Naturally<br />
occurring antimicrobial peptides cannot be used in clinical settings<br />
because they are often toxic to mammalian cells, but Lam and her<br />
team wanted to use them as a model for designing a powerful and safe<br />
antibiotic agent.<br />
The scientists meticulously designed the polymers down to the level<br />
of the individual building blocks—amino acids—that would make up<br />
the peptides. Out of the many amino acids available to them, the scientists<br />
chose lysine and valine. Lysine is a positively charged cation and<br />
was selected because cationic peptides were already known to exhibit<br />
antimicrobial activity. Valine, on the other hand, is uncharged and<br />
therefore hydrophobic, meaning it does not interact favorably with<br />
water or other polar molecules. Since hydrophobic materials interact<br />
favorably with other hydrophobic materials, valine’s hydrophobicity<br />
enables the SNAPPs to infiltrate the cell membrane, which is also<br />
mostly hydrophobic. Instead of just creating long chains of amino acids<br />
or allowing the polymers to self-assemble, the researchers attached<br />
groups of 16 or 32 chains to a multifunctional core, which served to<br />
promote water solubility and create the characteristic star shape. They<br />
hypothesize that the star shape optimizes functionality because it promotes<br />
peptide aggregation and localized charge concentration, which<br />
leads to more effective ionic interactions with bacterial membranes.<br />
After designing and successfully producing the polymers, the researchers<br />
assessed the activity of the SNAPPs against different species<br />
of bacteria. The SNAPPs were active against all bacterial species but<br />
were especially effective against Gram-negative bacteria, such as E.<br />
coli. Gram-negative bacteria are characterized by an outer membrane<br />
that normally acts as a highly impermeable barrier, but the researchers<br />
discovered that the SNAPPs could penetrate this membrane, since<br />
they have a high affinity for specific molecules found on it. The treatment<br />
was equally effective against antibiotic-resistant and susceptible<br />
strains of bacteria. The effectiveness of SNAPPs against Gram-negative<br />
bacteria is especially important because no antibiotic drugs currently<br />
under development are effective against Gram-negative infections.<br />
Before testing SNAPPs in living organisms, the researchers first performed<br />
a biocompatibility assay to ensure that the polymers would<br />
not attack mammalian cells. By incubating the polymers with sheep’s<br />
blood and measuring death rates of blood cells, the scientists determined<br />
that SNAPPs exhibit very low toxicity, even at concentrations<br />
100 times higher than what is required to kill bacteria. After confirming<br />
biocompatibility, they tested the effectiveness of SNAPPs by<br />
treating mice with rampant bacterial infections. The results were very<br />
promising—all mice treated with SNAPPs lived, compared to only<br />
20 percent of the untreated mice. In addition, SNAPP treatment enhanced<br />
the ability of white blood cells to infiltrate infected tissues, a<br />
benefit not displayed by mice treated with traditional antibiotics.<br />
The SNAPPs have multiple mechanisms of killing cells, making it<br />
more difficult for bacteria to develop resistance against them. The<br />
polymers’ partially hydrophobic composition allows them to infiltrate<br />
the membrane, but once they have done so, the positively charged<br />
amino acids disrupt membrane integrity and prevent regulation of ion<br />
flow. The star-shaped polymers can even aggregate and rip apart the<br />
membrane. The SNAPPs may also trigger the cellular processes that<br />
induce apoptosis, or cell suicide. All these mechanisms of antibiotic<br />
action are impressive individually, but when combined in a single molecule,<br />
they are incredibly powerful and difficult for bacteria to fight.<br />
Even after exposing 600 generations of bacteria to low concentrations<br />
of SNAPPs, the researchers could not detect bacterial resistance to the<br />
treatment. These results show great promise for SNAPPs as a longterm<br />
solution to the rise of superbugs.<br />
To bring treatments like SNAPPs into regular use, more research,<br />
development, and eventually clinical trials are needed. Although many<br />
industries and the public still fail to heed scientists’ warnings about antimicrobial<br />
resistance, governments and research institutions are starting<br />
to focus on the war against drug-resistant bacteria. On September<br />
21st, the United Nations held a summit on antimicrobial resistance<br />
and concluded that all countries must formulate a plan to combat it.<br />
At the beginning of October, the CDC announced that a Yale School of<br />
Public Health research team—along with 33 other teams—will receive<br />
funding as part of a $14 million effort to research antibiotic resistance.<br />
Hopefully, this collaboration between scientists and governments will<br />
allow SNAPPs—and perhaps other new technologies—to better aid in<br />
humanity’s battle against antibiotic-resistant bacteria.<br />
IMAGE COURTESY OF WIKIMEDIA COMMONS<br />
►Scanning electron micrograph image of methicillin-resistant<br />
Staphylococcus aureus (MRSA). MRSA is one of the most well-known<br />
drug-resistant bacteria and is especially common in hospitals and<br />
sports settings.<br />
www.yalescientific.org<br />
December 2016<br />
Yale Scientific Magazine<br />
31
FEATURE<br />
astronomy<br />
SHEDDING LIGHT ON A<br />
BIZARRE<br />
STAR<br />
BY THEO KUHN<br />
32 Yale Scientific Magazine December 2016 www.yalescientific.org
From space, most stars never twinkle. Some dim periodically, betraying<br />
the clocklike passage of planets. But there is one star that flickers<br />
unlike any other seen before. Known as “Tabby’s Star,” this astronomical<br />
enigma has captured the imaginations of thousands of scientists<br />
and amateurs alike. Its mysterious blinking behavior was first spotted<br />
by amateurs and was subsequently investigated by former Yale postdoctoral<br />
fellow Tabetha Boyajian ’16. Because the behavior of Tabby’s Star<br />
is completely unlike that of similar stars, scientists have resorted to an<br />
array of wild theories as potential explanations—from a massive comet<br />
chain to an alien megastructure. New research suggests that the star is<br />
even more peculiar than previously thought, complicating attempts to<br />
explain its behavior and reinforcing the need for continued study of its<br />
idiosyncrasies.<br />
Tabby’s Star (more formally known as KIC 8462852, and more colloquially<br />
as the “WTF”—Where’s The Flux?— Star) was observed from<br />
2009 to 2013 by NASA’s Kepler Space Observatory. This orbiting telescope<br />
is designed to detect the shadows of exoplanets as they pass in<br />
front of stars. But because of its foreign behavior, Tabby’s Star was not<br />
detected automatically; it took the relatively untrained eyes of citizen<br />
scientists—amateur astronomy enthusiasts who volunteered to pore<br />
through Kepler’s data with their own eyes—to spot the bizarre signal.<br />
“When they first showed the data to me, I just thought it was bad data”,<br />
Boyajian said. “Our automated pipelines missed this feature because it<br />
was unlike anything we had seen before,” she added.<br />
So just what is it about Tabby’s Star that is so perplexing? Most stars<br />
exhibit small, periodic, and symmetrical dips in their brightness, if they<br />
exhibit observable periods of dimness at all. These dips are the result of<br />
the regular passage of an orbiting planet in between the star and the telescope,<br />
a planetary eclipse of sorts. But research by Boyajian demonstrated<br />
that Tabby’s Star exhibits frequent and irregular dips in its brightness<br />
too large to be caused by a planet. New research led by postdoctoral researcher<br />
Benjamin Montet of the University of Chicago revealed another<br />
feature not seen in any nearby or similar stars: a dramatic, long-term<br />
dimming over the four-year course of the Kepler study.<br />
The sum of these observations leads to a troubling but fascinating dilemma:<br />
nothing like Tabby’s Star has been seen before, and no single<br />
theory can make sense of all of the star’s unique characteristics. “There is<br />
no good explanation for what’s going on,” Boyajian said. All explanations<br />
must involve an event far larger than anything of its kind seen before,<br />
or a controversial phenomenon that has been theorized but never observed.<br />
One of the favored explanations presented by Boyajian’s team<br />
consists of a comet swarm around the star that causes its fluctuations<br />
in brightness; however, all comet swarms observed so far are hardly a<br />
tenth of the size that would be necessary to produce such a large signal.<br />
The most well-known explanation for the star’s behavior is an energy<br />
harvesting system built by extraterrestrial life (known as a Dyson sphere<br />
or Dyson swarm). That said, any theory of such elaborate proportions,<br />
particularly one based on phenomena that have yet to be observed, must<br />
be regarded with suspicion.<br />
When Kepler refocused in 2013 on a new mission, it appeared that<br />
researchers would have to rely on only four years of data to solve this<br />
astronomical Rubik’s cube. But once again, astronomy enthusiasts came<br />
to the rescue: a Kickstarter project initiated by Boyajian raised over<br />
$100,000—enough to fund a year of constant observation of the star<br />
through Las Cumbres Observatory Global Telescope Network. With<br />
continuous monitoring of Tabby’s Star at multiple wavelengths, Boyajian’s<br />
team will be able to observe long-term trends. They will also be able<br />
to react in real time to short-term changes in the star’s intensity, which<br />
astronomy<br />
FEATURE<br />
wasn’t possible during the Kepler observations. Sudden changes will set<br />
off a “real-time trigger” that will cue the team to take a burst of higher<br />
resolution images, allowing them to better capture unprecedented rapid<br />
fluctuations in the star’s brightness. Subsequent analyses of these images<br />
have the potential to shed light on the cause of these fluctuations.<br />
While conclusions regarding Tabby’s Star are pending further observation,<br />
one message has already manifested: citizen science is a force<br />
with which to be reckoned. The discovery of Tabby’s Star and its continuing<br />
observation are the result of the massive amount of support that<br />
astronomy enthusiasts can provide; in addition being tracked by the<br />
global network of professional telescopes, Tabby’s Star will be monitored<br />
by the American Association of Variable Star Observers (AAVSO), an<br />
organization comprised primarily of amateurs.<br />
There are, of course, limitations to citizen science in the realm of astronomy.<br />
AAVSO is providing observations of Tabby’s Star to Boyajian’s<br />
team, collected by the home-operated telescopes of astronomy enthusiasts.<br />
Though these observations are useful, they are not as sophisticated<br />
or coordinated as those provided by a professional network. While this<br />
data may prove to be a helpful supplement, AAVSO is unable to provide<br />
a “real-time trigger” in the way that the Las Cumbres Observatory Global<br />
Telescope Network can. The numerous observation stations operated<br />
by AAVSO are not entirely standardized. As a result, observations from<br />
one station are systematically offset from others, precluding the use of<br />
AAVSO to identify short-term fluctuations.<br />
But what citizen science lacks in finesse, it makes up for in both manpower<br />
and willpower. “We were quite surprised by how many people<br />
were interested in supporting this project,” Boyajian said. Unlike many<br />
citizen scientist projects that rely on the human brain’s exceptional<br />
ability to recognize patterns in images— ‘pretty pictures,’” as Boyajian<br />
termed it—signing up for the Kepler project guaranteed hours of staring<br />
at graphs. That didn’t stop over 300,000 citizen scientists from contributing<br />
to the project and from being the first to spot this bizarre star. “Not<br />
a lot of astronomers take advantage of this immense resource,” Boyajian<br />
said. “I can definitely see citizen-science like this growing in the future.”<br />
IMAGE COURTESY OF WIKIMEDIA<br />
►A theoretical diagram of Dyson Rings, an extraterrestrial energy<br />
harvesting device that has been proposed as a possible, albeit farfetched,<br />
explanation for the observations of Tabby’s Star.<br />
www.yalescientific.org<br />
December 2016<br />
Yale Scientific Magazine<br />
33
COUNTERPOINT<br />
TIGHT JEANS? DON’T BLAME YOUR GENES<br />
►BY LUCINDA PENG<br />
The prevalence of obesity and Type 2 diabetes has been increasing for<br />
at least 50 years. Attempting to explain this trend from an evolutionary<br />
perspective, researchers developed the “thrifty gene hypothesis”: the<br />
idea that evolution selected for genes that promote fat storage as an<br />
evolutionary advantage during famines.<br />
The hypothesis originated in 1962, when James Neel proposed that<br />
modern living conditions had created an evolutionary mismatch,<br />
which occurs when genes that once were advantageous become<br />
deleterious in a new environment. He concluded that this mismatch<br />
had contributed to an increase in Type 2 diabetes, and his hypothesis<br />
was the first widely discussed idea on the subject. However, in 1989,<br />
Neel reviewed his own work and realized that his hypothesis was<br />
probably incorrect, for famines occurred too infrequently to have<br />
generated significant selection pressure. Since then, the theory has<br />
been put aside in favor of other hypotheses, and the new results<br />
discussed below solidify that move.<br />
Guanlin Wang and John Speakman of the Chinese Academy of<br />
Sciences found genetic evidence opposing the thrifty gene hypothesis.<br />
They examined 115 single nucleotide polymorphisms (SNPs), or<br />
common genetic mutations, that had previously been found to be<br />
correlated with obesity. They used genomes from a database compiled<br />
by the 1000 Genomes Project, an international collaboration to<br />
document genetic variability among different ethnicities, to ensure<br />
that effects of specific subpopulations did not influence their results.<br />
When Wang and Speakman analyzed the SNPs associated with a<br />
higher body mass index (BMI) in obese and control populations, they<br />
found no significant selection for these genes, suggesting that evolution<br />
has not selected for obesity. In fact, of the nine genes associated with<br />
IMAGE COURTESY OF WIKIMEDIA COMMONS<br />
►Calorie dense junk food has contributed to the rise of type 2<br />
diabetes and obesity.<br />
BMI, five of them had decreased, rather than increased, fat storage.<br />
Their discovery is not consistent with the genetic basis of the thrifty<br />
gene hypothesis, increasing the plausibility of other theories about<br />
the underlying causes of obesity. Dr. Stephen Stearns, Yale professor<br />
of Ecology and Evolutionary Biology, cites two other hypotheses to<br />
replace the thrifty gene hypothesis: the thrifty phenotype and the<br />
hygiene hypotheses.<br />
Hales and Baker proposed the thrifty phenotype hypothesis in 1992,<br />
suggesting that the body uses information from the environment<br />
early in life to predict its needs for the future environment. These<br />
environmental conditions can induce epigenetic changes, or<br />
nongenetic mechanisms, that affect phenotypic (observable) traits.<br />
They found that babies born during the Dutch Hunger Winter, a<br />
six-month food blockade by the Germans in the Netherlands, were<br />
more prone to insulin resistance due to a nutritional deficit in the<br />
womb. Insulin promotes the absorption of sugar from blood into<br />
tissues, but under starvation conditions, nonessential tissues become<br />
less responsive to insulin so that the brain can receive enough sugar.<br />
When the Germans left, food was abundant, so the environment that<br />
the baby was prepared for did not match the environment it was born<br />
into. As a result, the people born in this period were more prone to<br />
diabetes and other diseases. “This trend can be observed under normal<br />
circumstances, too, as birth weight is a good predictor of the risk of<br />
being affected by diseases later in life,” said Dr. Stearns. The thrifty<br />
phenotype hypothesis addresses a major problem from the thrifty<br />
genotype hypothesis. If there had been continued, strong positive<br />
selection for increased fat storage, all humans would be obese because<br />
these genes would be fixed, or permanently added to the human<br />
genome. In contrast, with “thrifty phenotypes,” epigenetic factors are<br />
affected by the environment and can vary among people.<br />
The hygiene hypothesis relates the gut microbiota to metabolic<br />
diseases. The gut microbiota is composed of bacteria that help to<br />
break down macromolecules and absorb nutrients; it is sensitive<br />
to environmental stimuli. For example, babies born by C-section<br />
rather than vaginal birth have different microbiota because they were<br />
not exposed to the bacteria in their mother’s birth canal, and being<br />
breastfed or taking antibiotics can also affect a baby’s gut microbiota.<br />
These changes have been shown to affect their risk of obesity, insulin<br />
resistance, and Type 2 diabetes.<br />
With a lack of genetic evidence to support the claim that humans<br />
evolved to better store fat, the thrifty phenotype and hygiene hypotheses<br />
are now favored to replace the thrifty genotype hypothesis. Wang and<br />
Speakman’s paper provides more concrete evidence to refute the thrifty<br />
gene hypothesis, supporting what many scientists already believed.<br />
Because the thrifty phenotype and hygiene hypotheses explain why<br />
metabolic diseases can be inherited but are also heavily influenced by<br />
the environment, they provide a more robust explanation for the rise<br />
in obesity and Type 2 diabetes.<br />
34 Yale Scientific Magazine December 2016 www.yalescientific.org
BLAST<br />
from<br />
the<br />
PAST<br />
Malaria: Finding the Missing Pieces of Malaria’s Migratory Patterns<br />
►BY WILL BURNS<br />
In 1925, Spain’s Catalan Government set up a humble<br />
hospital in the Ebro Delta region. The hospital treated<br />
patients suffering from malaria. Ildefonso Canicio, a<br />
doctor at the hospital, spent decades diagnosing and<br />
treating patients. By drawing blood from patients,<br />
and placing a drop on a microscope slide, he could<br />
determine whether the blood contained Plasmodium,<br />
the parasite that causes malaria.<br />
Canicio threw away most of his slides, but he kept<br />
a few slides from the 1940s. Little did he know that<br />
seventy years later, these slides would provide insight<br />
into the global migratory patterns of the malaria<br />
Plasmodium.<br />
To fight malaria in the present day, researchers are<br />
looking to the past to understand how the parasite<br />
evolved over time, specifically exploring how human<br />
movements transmitted the parasite across the globe.<br />
Malaria was successfully eradicated from Europe after<br />
World War II. Thus, researchers have had to search<br />
for old, badly preserved slides from Europe’s preeradication<br />
era, hoping to find clues about the nowextinct<br />
parasite.<br />
Carles Lalueza-Fox, a paleo-genomics researcher<br />
at the Institute of Evolutionary Biology in Barcelona,<br />
reached out to Canicio’s family who gave him three<br />
slides to analyze. Back at the lab, he quickly realized<br />
that analyzing the slides would be difficult. “There<br />
were just a few drops of blood in the samples. Once<br />
they were extracted and sequenced, they were gone.<br />
The slides were fragile and covered with stains and<br />
oils,” said Lalueza-Fox.<br />
Despite the fragility and small size of the samples,<br />
Lalueza-Fox and his team successfully obtained<br />
a huge amount of genetic data from Plasmodium<br />
mitochondrial DNA (mtDNA). Unlike nuclear DNA,<br />
mtDNA is inherited only from the mother, so it is<br />
better suited for determining the maternal lineage<br />
and genealogy of a species. “As far as I know, this is<br />
the first study where such old slides were used and<br />
such an amount of genetic data from the pathogens<br />
was retrieved,” Lalueza-Fox added.<br />
Using the reconstructed European Plasmodium<br />
mtDNA genomes, Lalueza-Fox and his team shed light<br />
on certain controversies surrounding the parasite’s<br />
evolutionary history. “It was not clearly understood<br />
how the pathogen spread along different continents,<br />
because Europe was central to some of these dispersals<br />
but no data from Europe was available,” noted Lalueza-<br />
Fox.<br />
His team found surprising genetic similarities<br />
between European Plasmodium mtDNA and Indian<br />
Plasmodium mtDNA. Lalueza-Fox believes that<br />
malaria was transmitted from India to Europe when<br />
the Persian Empire expanded into India in the sixth<br />
century BCE.<br />
The team also found evidence that European,<br />
Central American, and South American parasites<br />
are genetically similar–indicating that, the exchange<br />
of food, plants, culture, and technology between the<br />
Old World and the Americas in the 15th and 16th may<br />
have helped spread malaria.<br />
Lalueza-Fox is now attempting to construct the<br />
nuclear genome of the European Plasmodium<br />
parasite. “So far, we have about 40 percent of the<br />
nuclear genome of the P. falciparum. I reckon we need<br />
four or five more slides,” Lalueza-Fox said.<br />
In Lalueza-Fox’s opinion, understanding the<br />
nature of parasites from 100 years ago is critical for<br />
understanding the resistance of modern parasites to<br />
treatment. “Plasmodium is a very dynamic organism<br />
and very difficult to tackle because of these mutations,”<br />
Lalueza-Fox added.<br />
His team will continue to search for the missing<br />
pieces of the Plasmodium “puzzle,” researching the<br />
extinct parasite to enhance our understanding of<br />
malaria.<br />
www.yalescientific.org<br />
December 2016<br />
Yale Scientific Magazine<br />
35
UNDERGRADUATE PROFILE<br />
DEVIN CODY (SM’17)<br />
IT REALLY IS JUST ROCKET SCIENCE<br />
►BY ELIZABETH RUDDY<br />
Ten. Ten Yalies begin the countdown, holding their breath,<br />
praying. Nine. A lone rocket sits in an endless expanse of canyonfilled<br />
wilderness. Eight. They smile, their eyes never straying from<br />
Chronos, awaiting the culmination of their year of work. Seven. Six.<br />
The numbers fly, tumbling out of their mouths. Five. Four. Three.<br />
The exhilaration builds. Two. All they can do now is watch. One.<br />
Devin Cody, now a senior double majoring in Electrical<br />
Engineering and Applied Physics, remembers that day in June<br />
of 2014 clearly. The competition rocket team, a subset of the Yale<br />
Undergraduate Aerospace Association (YUAA), launched Chronos,<br />
a rocket which they had been developing for months, seven thousand<br />
feet into the air, earning second place at the Intercollegiate Rocket<br />
Engineering Competition. The objective of their launch was to test<br />
general relativity using two atomic clocks. They hoped that the clock<br />
in the rocket would tick slower (on the scale of ten trillionths of a<br />
second) relative to the clock on the ground due to time dilatation,<br />
a physics framework that dictates how time passes differently in<br />
different reference frames. Although the data from the clocks was<br />
ultimately inconclusive, the launch itself was successful.<br />
For Cody, launching Chronos was a thrilling experience. “It was<br />
exhilarating to see our rocket fly into the air at close to the speed of<br />
sound, just praying that the parachutes would deploy,” said Cody.<br />
Since the launch, he has become an active member of the YUAA. He<br />
served as one of the group’s co-presidents during his junior year, and<br />
he continues to serve as a senior advisor on their executive board<br />
this year.<br />
PHOTOGRAPHY BY GEORGE ISKANDER<br />
►Devin Cody serves as a senior advisor on the Yale Undergraduate<br />
Aerospace Association’s executive board.<br />
During his sophomore year, Cody was selected to lead a YUAA<br />
project to build a radio telescope. He drew on his experiences from<br />
the previous summer at the National Radio Astronomy Observatory<br />
in West Virginia, where he helped improve the accuracy of<br />
telescopes by developing code to both detect and correct errors and<br />
malfunctions. At Yale, Cody’s 16 person team designed and built an<br />
8 foot telescope, complete with a mount, receiver, and control code.<br />
“That was a really cool project for me because I got to work with<br />
some incredible engineers at Yale and with people who became some<br />
of my closest friends,” said Cody. The telescope currently sits on the<br />
roof of the Yale Leitner Observatory and Planetarium.<br />
Cody’s favorite research, however, was the work he did this summer<br />
with the Avionics and Hardware Engineering group of SpaceX,<br />
a private company currently pushing the boundaries of aerospace<br />
technology. SpaceX aims to bring down the cost of access to space by<br />
developing technology that will enable rocket reusability. At SpaceX,<br />
Cody developed an Electromagnetic Compatability (EMC) testing<br />
apparatus to test whether a coaxial cable provided adequate shielding.<br />
While he was there, Cody tested which shielding mechanisms were<br />
the most effective, research that was in great demand by members<br />
in other groups within SpaceX. “It was incredible seeing the impact<br />
that my work had almost immediately,” said Cody. “I think you<br />
realize your work matters when you have people from the other side<br />
of the company pushing you to get your work done fast because they<br />
need your results to make informed decisions about their work.”<br />
Well into his senior year at Yale, Cody is now exploring another<br />
passion, quantum computing. Together with Professor Michel<br />
Devoret, he is studying quantum bits (qubits) in order to determine<br />
their properties. Qubits are similar to regular computer bits—<br />
both are small units of data used to store information and execute<br />
instructions. However, qubits are used in quantum computers and<br />
are potentially capable of more efficient calculations. To investigate,<br />
Cody and a graduate student from Devoret’s lab are designing a<br />
computationally efficient method of optimizing qubit design.<br />
Devin Cody will graduate from Yale this spring with a double<br />
major in Applied Physics and Electrical Engineering and copious<br />
work experience at the National Radio Astronomy Observatory,<br />
SpaceX, NASA, and the Yale Quantum Institute. When asked about<br />
his plans for after Yale, Cody laughed. “It’s a valid question, I don’t<br />
have many answers just yet. I’m not entirely sure what I want to<br />
do… definitely electrical engineering.” But even within electrical<br />
engineering, Cody is certainly not tied to any one area, and it will be<br />
fascinating to see in which direction he chooses to launch.<br />
36 Yale Scientific Magazine December 2016 www.yalescientific.org
ALUMNI PROFILE<br />
DR. RALPH GRECO, M.D. ‘68<br />
CARING FOR THE CARETAKERS<br />
►BY ANUSHREE AGRAWAL<br />
Dr. Ralph Greco, a talented physician at Stanford Medical School,<br />
conducts research, but his biggest contribution to the field of medicine<br />
does not involve a pipette. Greco’s biggest contributions have<br />
been his improvements to the surgical residency program at Stanford.<br />
When asked about his motivation for researching resident wellbeing,<br />
Ralph Greco recites the chilling story of a promising student’s<br />
suicide. This incredibly talented man had graduated from the Stanford<br />
program and was completing further training in Chicago when<br />
he died. Greco recalls the memorial service he held in his house as<br />
particularly somber since the resident had left notes for his parents,<br />
recounting the verbal abuse he experienced daily from a surgeon in<br />
the program.<br />
The history of resident abuse can be charted back to a specific doctor<br />
from the 1800s. Greco cites surgeon William Stewart Halsted as<br />
the father of both the modern residency program and the cruelty<br />
associated with it. Greco’s theory is that Halsted’s implementation<br />
of the residency program at Johns Hopkins University had a basis in<br />
verbal abuse and authoritarian behavior, likely the result of his cocaine<br />
addiction. Because Halsted formally trained the first chairs of<br />
many medical schools, the cycle of abusive role models continued.<br />
After his resident died, Greco wanted to create a change and prevent<br />
further resident abuse.<br />
Greco, along with other esteemed academics interested in resident<br />
wellbeing at Stanford, began to break the cycle. Stanford was among<br />
the first institutions to implement a mandatory 80-hour workweek<br />
for residents: a precedent that other medical schools soon followed.<br />
He also created the Balance in Life program at Stanford—a program<br />
focused on promoting physical, psychological, professional, and social<br />
balance among residents through events, mentorships, healthy<br />
food and mental health initiatives. Since then, Greco has devoted<br />
the latter part of his career to improving the residency system, and<br />
he hopes to stop mentors from participating in abusive behavior targeted<br />
at residents.<br />
Not all medical professionals support Greco’s intentions, however.<br />
Greco recognizes that hospitals are reluctant to pour money into resident<br />
wellbeing—and into medical schools in general—because they<br />
want to maintain their efficiency. He has also had difficulty changing<br />
the mindset of doctors who once dealt with abusive behavior themselves.<br />
“Just as people who are abused sometimes become abusive<br />
parents, and learn to do that, this mindset becomes part of the upbringing,”<br />
Greco explains. The cycle is difficult to break.<br />
Greco has not limited himself to the pursuit of scientific endeavors.<br />
He is also an avid sculptor, and has been since he picked up the<br />
IMAGE COURTESY OF RALPH GRECO<br />
►Dr. Ralph Greco is a physician at the Stanford School of Medicine,<br />
where he has started the Balance in Life program to improve resident<br />
wellbeing.<br />
hobby at Princeton when an art teacher “took him under her<br />
wing.” Greco now considers stone his favorite medium. Art is extremely<br />
important to Greco, and he connects the activity to his focus<br />
on resident wellbeing. By pursuing his passion for art, he hopes to<br />
model a healthy work-life balance and show residents and doctors<br />
that they can make time for the hobbies that they love. He admits<br />
that finding this balance is difficult during residency, but creating a<br />
foundation for students to have a healthy mindset is critical.<br />
Greco cites Yale as an important place that opened doors for him<br />
as a physician scientist. He still talks with friends from medical<br />
school, and he continues to attend reunions. Greco plans to formally<br />
retire from Stanford next year, but he does not anticipate problems<br />
with his program after his retirement. He has already recruited the<br />
next leader of the program, and Greco is confident that she will continue<br />
working to educate residents and improve their lives at work.<br />
In retirement, Greco hopes to advance his artistic prowess and continue<br />
creating stone sculptures, although he does point out that stone<br />
is not the lightest material to work with.<br />
www.yalescientific.org<br />
December 2016<br />
Yale Scientific Magazine<br />
37
FEATURE<br />
book review<br />
SCIENCE IN THE SPOTLIGHT<br />
BOOK REVIEW: I CONTAIN MULTITUDES<br />
►BY SARAH ADAMS<br />
Until recently, microbes were primarily seen as carriers of sickness<br />
and disease. However, with technological advances and a few key<br />
discoveries that have highlighted their potential for medicine, microbes<br />
are now in the research spotlight. Ed Yong explores the nature of the<br />
close relationship between bacteria and animals in his new book I<br />
Contain Multitudes: The Microbes Within Us and a Grander View of<br />
Life.<br />
Yong begins by discussing the sheer ubiquity of microbes, thousands<br />
of which exist in the air, food, water, and even on this page. Then, he<br />
weaves a narrative that follows how microbes affect our bodies: how<br />
we maintain and manipulate our relationship with them, the benefits<br />
we reap from this relationship, and what happens when it fails. His<br />
chapter on horizontal gene transfer, the movement of genes from<br />
one organism to another without a parental-offspring relationship,<br />
was particularly interesting. He included an example of Bacteroides<br />
plebeius, a bacterium common throughout the world, and Zobellia<br />
galactanivorans, a bacterium found on seaweed. In the Japanese<br />
population, which consumes seaweed more regularly than the rest of<br />
the world, Zobellia has transfered the genes responsible for seaweed<br />
digestion to Bacteroides, which resides in the gut of the Japanese<br />
population.<br />
Yong also weaves an interesting narrative about the Wolbachia<br />
bacterium into the book. “Wolbachia is so fascinating because<br />
of how widespread it is and how it plays important roles in human<br />
PODCAST REVIEW: ARE WE THERE YET?<br />
►BY PAUL HAN<br />
disease,” said Yong. It is heralded as<br />
one of the most successful microbes<br />
on the planet because of its presence<br />
in 40 percent of insect and arthropod<br />
species. It originally did not have a<br />
practical medical application when it<br />
was first discovered but has recently<br />
been found to be able to potentially<br />
treat tropical diseases like the Dengue<br />
fever. “The whole story is a testament<br />
to science that does not have to have an<br />
immediate and practical application,”<br />
said Yong.<br />
In I Contain Multitudes, Yong<br />
IMAGE COURTESY OF ED YONG<br />
nods to past, notable discoveries in<br />
microbiology research, while incorporating examples of current<br />
research that connect to his themes. He also introduces a refreshing<br />
feeling of wonder—a feeling that is often ignored in books on<br />
similar topics—by highlighting the beauty of these microbial-animal<br />
interactions. “I wanted to get people to appreciate how interesting<br />
microbes are, rather than viewing them as sources of disease or dirt,<br />
to actually realize that they are important parts of the world around<br />
us. We should embrace that they are the dominant form of life on the<br />
planet with profound influences on the way life works,” said Yong.<br />
In popular science, few things are as romanticized as space exploration.<br />
It is the classic science fiction plot: the fearless captain and his loyal crew,<br />
journeying where no man has gone before. Yet to the average American,<br />
space exploration appears to be beyond our grasp, a distant, fanciful<br />
possibility in the drudgery of day-to-day life.<br />
A new podcast is hoping to change that perception. “Are We There<br />
Yet,” hosted by Brendan Byrne, follows the multifaceted efforts of<br />
interplanetary space travel, ranging from NASA’s New Horizons Probe<br />
to Elon Musk’s mission to Mars. Through informative discussion and<br />
interviews with the men and women at the forefront of space exploration,<br />
Byrne hopes to answer to question: “Are we there yet?”<br />
Byrne was inspired to start his podcast after researching NASA’s and<br />
other organizations’ plans to go to Mars. Byrne chose the podcast format<br />
over a traditional news segment so that he could explore his topics in<br />
greater detail. “I get the chance to really dig into these topics and not<br />
be constrained by time,” he explained. “I hope each episode inspires the<br />
listener to do some more exploring on their own.”<br />
Each week, Byrne introduces a topic, briefly shares his own perspective<br />
on the state and significance of the issue, and introduces his guest,<br />
whom he then interviews for the remainder of the podcast. His guests<br />
are typically scientists, researchers, and engineers from institutions such<br />
as NASA and Caltech’s Jet Propulsion Laboratory—all at the forefront of<br />
their field. They are courteous, intelligent, and highly informed.<br />
They are not, however, entertaining. While excellent sources of<br />
information, Byrne’s interviews are often dry and at times descend into<br />
jargon. While expert sources are an invaluable part of the show, the<br />
podcast would benefit from more speaking time for the host. When<br />
Byrne speaks, he immediately makes the subject more accessible. “I hope<br />
to take these insanely complicated technologies or plans and make them<br />
understandable,” he explained. He also understands the importance of<br />
public interest in the future of space exploration. “To succeed at space<br />
exploration, we need public support.” As a host, Byrne is excellent at<br />
exposing his listeners to these complicated technologies. He simply<br />
needs to put greater emphasis on making them accessible.<br />
While “Are We There Yet?” presents scientifically accurate and<br />
relevant information, it does not capture the audience’s imagination.<br />
There is promise, though. “We’re hoping to expand the show into a<br />
more produced and immersive experience,” he stated. If Byrne can<br />
execute his vision, “Are We There Yet” will be a compelling, entertaining,<br />
and informative program. Right now, however, it is more like a weekly<br />
fireside chat. For those captivated by the subject alone, however, this<br />
podcast is still worth a listen.<br />
38 Yale Scientific Magazine December 2016 www.yalescientific.org
cartoon<br />
FEATURE<br />
►BY ABHI MOTURI<br />
advertisement<br />
The Economy Doesn’t<br />
Affect Our Quality.
10% discount for all yale faculty and students<br />
call (203) 787-0400 or (203) 376-0356<br />
visit 50 Whitney Ave, New Haven, CT 06510