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Yale Scientific<br />

Established in 1894<br />


APRIL 2016 VOL. 89 NO. 3<br />



AGE<br />

introducing<br />

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computer of<br />

the future

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May 18, 2016<br />






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Yale Scientific Magazine<br />

VOL. 89 ISSUE NO. 3<br />


APRIL 2016<br />

NEWS 6<br />

FEATURES 25<br />


20<br />



Researchers from the Yale Quantum<br />

Institute integrate classical and<br />

quantum technologies, heralding a<br />

paradigm shift for the field.<br />

13<br />


OR FOE?<br />

With rising concern that robots will<br />

replace human workers, it is time to<br />

address this problem from all angles.<br />

16<br />



Yale researchers use zebrafish as a<br />

model organism in order to uncover<br />

a surprising relationship between<br />

autism and estrogen.<br />

18<br />

HOW DO WE<br />


Debates rage over the worth of<br />

environmentalism. Researchers call<br />

for a new methodology of valuing<br />

natural assets.<br />


23<br />



Yale study provides new strategies for<br />

avoiding excess sugar consumption<br />

along with insight on how to balance<br />

nutrition and taste in food products.<br />

More articles available online at www.yalescientific.org<br />

April 2016<br />

Yale Scientific Magazine<br />


q a<br />

&<br />


Since the December San Bernardino<br />

shooting, this question dominated national<br />

discourse. In order to gain important<br />

information, the FBI pressured Apple<br />

to unlock the iPhone of one of the shooters.<br />

Apple refused, claiming the backdoor<br />

decryption mechanism would jeopardize<br />

customers’ security. The case brought<br />

new attention to rising conflicts between<br />

privacy and security.<br />

Encryption via an electronic key ensures<br />

that only certain parties may access<br />

data. Therefore, encrypting a phone<br />

prevents anyone without the key from<br />

tampering with stored information. Often,<br />

the strength of encryption depends<br />

on the strength of the passcode. Longer<br />

strings of letters, numbers, and characters<br />

are less susceptible to popular hacking<br />

methods in which thousands of passwords<br />

are guessed each second.<br />

The simple four-digit passcodes many<br />

Is your data safe from the government?<br />


►Tim Cook, Apple’s CEO, publicly affirmed<br />

the company’s commitment to privacy.<br />

of us use to unlock our iPhones ought<br />

to be easy to crack by brute force. Recognizing<br />

this vulnerability, Apple introduced<br />

a fail-safe that erases all data<br />

on an iPhone after 10 failed passcode<br />

attempts. Hoping to forcibly crack the<br />

shooter’s iPhone, the FBI demanded Apple<br />

circumvent the fail-safe mechanism.<br />

Apple responded, asserting that this<br />

would violate employees’ Constitutional<br />

rights. However, it now seems that the<br />

question of whether or not the right to<br />

free speech extends to computer code<br />

will remain unanswered. A third party<br />

has reportedly unlocked the shooter’s<br />

iPhone without losing data, and the FBI<br />

dropped its case against Apple.<br />

Although this cyber-turf war has yet<br />

to play out, we ought to consider the<br />

questions it raised: what is more important,<br />

protecting privacy or protecting<br />

people?<br />

Are our phones and books hurting our eyesight?<br />


According to a recent study, 50 percent<br />

of the world’s population will suffer from<br />

myopia, or nearsightedness, by the year<br />

2050. Kovin Naidoo, contributing author<br />

from the Brien Holden Vision Institute,<br />

believes this development is driven primarily<br />

by changes in the human environment.<br />

“Society has moved from a rural to<br />

a predominantly urban environment and<br />

from spending time outdoors to relying<br />

on indoor activities, such as reading, computer<br />

games, TV, video games and mobile<br />

phones,” Naidoo said. However, nearsightedness<br />

need not be inevitable. Evidence<br />

suggests spending time outdoors can protect<br />

children from nearsightedness.<br />

Jennifer Galvin, Assistant Professor of<br />

Opthalmology at the Yale School of Medicine,<br />

also stresses the importance of preventing<br />

nearsightedness in adolescents,<br />

pointing to medications that effective-<br />


►By changing our children’s lifestyles, we<br />

may prevent the upward trend in myopia.<br />

ly delay it. “Pharmacological intervention,<br />

such as dilute Atropine treatment,<br />

can slow the progression of myopia,” she<br />

said. Atropine is a medication, typically<br />

administered through eyedrops, which<br />

may prevent myopia. Atropine is not yet<br />

FDA-approved for treating early myopia.<br />

Pediatric ophthalmologists should consider<br />

these recently studied medications,<br />

along with Naidoo’s work on the trends<br />

and environmental determinants, when<br />

deciding treatment plans for their patients.<br />

While his recent prediction may seem<br />

frightening, Naidoo stressed that the discovery<br />

should not prevent children from<br />

participating in indoor activities completely,<br />

but it should rather encourage a<br />

more well-rounded lifestyle. “Time indoors<br />

needs to be counterbalanced with<br />

appropriate time outdoors,” Naidoo said.

3<br />

F R O M T H E E D I T O R<br />

Machines powered by artificial intelligence will overtake humans within 100<br />

years, Stephen Hawking said at last year’s Zeitgeist conference. That, Hawking<br />

warns, could spell the end of the human race.<br />

Should we be concerned about smart robots? They may put people out jobs or<br />

even turn on their human creators. Yet they also promise to take on dangerous tasks,<br />

unburden us of chores, and perhaps transform education (pg. 13). Besides, the technology<br />

that goes into these smart machines is revolutionizing science. Thanks to<br />

machine learning technology, doctors can more accurately predict whether patients<br />

will suffer from potentially fatal bacterial infections (pg. 10). Machine learning was<br />

also behind AlphaGo’s defeat of Grandmaster Lee Sedol at a game once thought too<br />

complex for computers, a feat that lend further credibility to Hawking’s prediction.<br />

Supercomputers have been integral to much of this big data analysis and they<br />

are here to stay. But physicists and engineers are already imagining a radically new<br />

form of computers, one that exploits the enigmatic laws of quantum physics where<br />

bits can be 0 and 1 at the very same time. Yale researchers have crossed yet another<br />

milestone in the march towards true quantum computers (pg. 20), and the opening<br />

of the Yale Quantum Institute six months ago promises to energize research efforts.<br />

Quantum computers will give us the ability to solve problems that defy the most<br />

powerful supercomputers today. But they would also be able to break the cryptographic<br />

algorithms that secure much of our data. In many ways, this conundrum<br />

is akin to that posed by smart robots. How can harness the power of these new<br />

technologies while managing their risks and dangers?<br />

In these pages, we explore the science behind important breakthroughs but also<br />

make it a point to emphasize how policymakers need to guide the sciences. We<br />

report recent work suggesting that our natural resources are undervalued in policy<br />

analysis (pg. 18), along with research suggesting that regulators have been too ready<br />

to accept a BPA substitute that may in fact be just as harmful (pg. 34). We highlight<br />

the potential of an attempt to control mosquito populations by gene editing while<br />

observing the importance of drafting guidelines for such work (pg. 28). We cover a<br />

new Connecticut initiative, and applaud its goal of helping academics translate their<br />

research from bench to bedside (pg. 6).<br />

Whether you, like many of us, love science for its own sake, or whether you want<br />

to understand science and its implications for our world, we warmly welcome you<br />

on board a tour through these exciting times.<br />

A B O U T T H E A R T<br />

Lionel Jin<br />

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Yale Scientific<br />

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APRIL 2016 VOL. 89 NO. 3<br />



AGE<br />

introducing<br />

the byte-sized<br />

computer of<br />

the future<br />

Lines emblematic of the surface of a computer chip ensnare<br />

the cover of <strong>89.3</strong>, designed by arts editor Ashlyn<br />

Oakes. Once the stuff of thought experiments alone, rudimentary<br />

quantum computers have already been built.<br />

By making use of qubits, which can take on any of three<br />

states, these machines promise to revolutionize computer<br />

simulation and more. Researchers at Yale have now successfully<br />

designed the smallest quantum computer chip<br />

to date. Like future applications of the newly slimmed<br />

down quantum chip, the cover design extends out into<br />

the background beyond what we can see.<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 />

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NEWS<br />

in brief<br />

Biology Research in the Hands of Investors<br />

By Rose Bender<br />


►Dr. Craig Crews is the principal investigator<br />

of PITCH and Lewis B. Cullman<br />

Professor of Molecular, Cellular,<br />

and Developmental Biology at Yale.<br />

What can a biologist do with ten million<br />

dollars? Find new therapies for cancer? Treat<br />

inflammatory illnesses? Fight infectious<br />

diseases?<br />

Established in 2015, the Program in Innovative<br />

Therapeutics for Connecticut’s Health (PITCH)<br />

is working to accomplish all of these goals. The<br />

program aims to help scientists at Yale University<br />

and the University of Connecticut develop<br />

their research into new therapeutic drugs.<br />

Its founder and principal investigator, Craig<br />

Crews, approached the Connecticut Bioscience<br />

Innovation Fund with this idea in 2015. The<br />

group provided ten million dollars in funding<br />

over three years. In January 2016, the first 12<br />

projects were selected for further development.<br />

Crews, the L.B.Cullman Professor of<br />

Molecular, Cellular, and Developmental Biology<br />

at Yale, started the program to serve an unmet<br />

need in academia—attracting venture capital to<br />

help translate basic research into clinically useful<br />

drugs. He leads the Yale Center for Molecular<br />

Discovery (YCMD), which assists Yale biologists<br />

with large-scale, high-throughput projects. “It<br />

was clear to me that many projects could go<br />

beyond just the research tool phase if there were<br />

resources, if we could take the next step or two<br />

towards drug development,” Crews said.<br />

PITCH projects will have free use of YCMD’s<br />

services. “What we want to do is generate the<br />

minimal data package necessary to convince<br />

investors to invest and create a new biotech around<br />

this initial intellectual property,” Crews said.<br />

Crews learned from his experience in academia<br />

and business: in addition to teaching at Yale for<br />

over 20 years, he founded two biotechnology<br />

companies. His company, Proteolix, developed<br />

an FDA-approved cancer drug.<br />

Crews hopes PITCH will help other Yale faculty<br />

members create companies that are, like his own,<br />

based on original research. He aims to fund at<br />

least 36 projects over PITCH’s three years.<br />

Finding Air Quality for Quality Air<br />

By Lucinda Peng<br />


►The air sensors developed by Dr.<br />

Drew Gentner’s team will be placed<br />

around the test case city of Baltimore,<br />

Maryland.<br />

Despite the large variability of air quality<br />

across a city, most cities can only collect<br />

air quality data from a couple of sites, leading<br />

to a misrepresentation of air quality. A<br />

team of undergraduates led by Yale professor<br />

Drew Gentner is attempting to remedy<br />

this by creating stationary and portable air<br />

quality sensors through Yale’s new Solutions<br />

for Energy, Air, Climate, and Health<br />

(SEARCH) Center. SEARCH is funded<br />

by the Environmental Protection Agency<br />

(EPA) and focuses on the relationship between<br />

air quality, climate change, energy<br />

policy, and public health.<br />

Dr. Gentner’s team is designing the air<br />

pollutant monitors to be used in the case<br />

study city of Baltimore, Maryland, measuring<br />

the concentration of pollutants such<br />

as ozone, carbon dioxide, methane, nitrogen<br />

and sulfur oxides, and particulate<br />

matter less than 2.5 µm in diameter. Next<br />

year, the stationary sensors, which are each<br />

about the size of a shoebox, will be strategically<br />

placed around Baltimore to collect<br />

pollution data for several years, while the<br />

portable sensors, each about the size of a<br />

smartphone, will be worn by people for a<br />

few days.<br />

The data from the new sensors will map<br />

the city’s air quality in space and time,<br />

while data from the portable sensors will<br />

provide insight into what pollutants people<br />

most commonly come in contact with. This<br />

higher resolution mapping of air pollutants<br />

will help identify pollutant hot spots,<br />

allowing urban planners to design cities to<br />

minimize health risks for the population,<br />

and public health officials to better assess<br />

the health risks present in different areas of<br />

the city.<br />

6 Yale Scientific Magazine April 2016 www.yalescientific.org

in brief<br />

NEWS<br />

A New Way to Play: The Yale play2PREVENT Lab<br />

By Genevieve Sertic<br />

When people consider health problem<br />

prevention methods, video games are not<br />

what first come to mind—in fact, they are<br />

often thought to be associated with health<br />

problems. The relationship between video<br />

games and health, however, need not be<br />

a negative one. Yale associate professor of<br />

medicine Lynn Fiellin instead utilizes video<br />

games to prevent health issues such as HIV,<br />

drug abuse, and smoking.<br />

Fiellin founded the play2PREVENT Lab,<br />

an organization aiming to help children<br />

and teens learn about risk prevention and<br />

healthy living through evidence-based video<br />

game interventions. For example, the<br />

first of these games, “PlayForward: Elm City<br />

Stories,” allows players to make a virtual avatar<br />

and places them in situations like a chaotic<br />

party or their first job, where they make<br />

decisions beneficial or detrimental to their<br />

health.<br />

Fiellin was inspired to use video games<br />

as a prevention method because of her experience<br />

with her own children. “Everyone<br />

was on a device and…playing games, so it<br />

seemed like the perfect way to reach youth,”<br />

Fiellin said. Fiellin’s instinct has proven effective,<br />

as the games developed by the lab<br />

have received overwhelmingly positive responses<br />

from youth, parents, and teachers<br />

alike.<br />

The lab has also received institutional<br />

recognition. The Yale School of Medicine<br />

recently established the Yale Center for<br />

Health & Learning Games, which incorporates<br />

the work of the play2PREVENT Lab.<br />

Fiellin is the director of the new center. “We<br />

hope to build on this program so that our<br />

impact can further be demonstrated in the<br />

next generation of scientists working in the<br />

field of serious or transformational games,”<br />

Fiellin said.<br />


►Lynn Fiellin develops video games<br />

at the play 2PREVENT Lab that aim<br />

to prevent health problems such as<br />

smoking and HIV.<br />

Dkk-1: A New Target for Disease Therapy?<br />

By Natalia Zaliznyak<br />

Have you ever thought about how the human<br />

body manages to protect itself from the<br />

myriad of diseases and infections that could<br />

attack its cells at any given moment? The key<br />

player in this defense is the immune system,<br />

which is responsible for the expulsion of antigens<br />

from the body. Paradoxically, however,<br />

this system also plays a role in the development<br />

of chronically destructive conditions<br />

like autoimmune diseases, asthma, and cancer.<br />

In a novel study, researchers from Yale professor<br />

Alfred Bothwell’s laboratory have shown<br />

that the protein Dkk-1, which is secreted by<br />

platelets, is important to the control of the<br />

immune system, influencing the development<br />

of inflammatory diseases. Chae, Bothwell,<br />

and colleagues demonstrated that near-total<br />

systemic removal of Dkk-1 reduced the severity<br />

of inflammation in mice with induced<br />

symptoms of asthma and a parasitic skin infection<br />

called Leishmaniasis, a lesion-causing<br />

chronic disease. This finding establishes a direct<br />

connection between the immune system<br />

and platelets, which are usually characterized<br />

by their involvement in blood clotting rather<br />

than inflammation.<br />

This work also suggests that Dkk-1 is a<br />

promising target for treatments of inflammatory<br />

diseases: small-molecule inhibitors of<br />

Dkk-1, which bind to the protein in a way that<br />

inactivates it, can potentially act as drugs to<br />

treat conditions caused by elevated levels of<br />

the protein.<br />

“It…has [a] surprising ability to regulate the<br />

immune system… So this [protein] is probably<br />

very relevant to asthma, as we’ve shown,<br />

and autoimmunity, atherosclerosis, and various<br />

types of cancers,” Bothwell said. “I don’t<br />

know of a comparable molecule, frankly.”<br />


►Human blood contains, among<br />

other things, red blood cells, white<br />

blood cells, and platelets. Platelets<br />

appear small and disc-shaped.<br />

www.yalescientific.org<br />

April 2016<br />

Yale Scientific Magazine<br />


NEWS<br />

geology<br />


The life story of Earth’s magnetic field<br />


Most of us are familiar with the Earth’s magnetic field<br />

as an invisible force directing our compasses north. But<br />

800,000 years ago, following the red needle of a compass<br />

would have sent you south. Back another 200,000 years<br />

and your compass would point north once again.<br />

Why the changes in direction? The Earth’s magnetic<br />

field, produced by turbulent motions deep in Earth’s<br />

interior, is susceptible to reversals in polarity due to<br />

instabilities in the liquid outer core.<br />

New research by Yale geology & geophysics professor<br />

David Evans and former Yale postdoctoral researcher<br />

Peter Driscoll of the Carnegie Institution provides an<br />

account of these reversals through much of Earth’s<br />

history. The researchers view their work as a sort of<br />

biography for the Earth’s magnetic field: an unstable<br />

and murky adolescence roughly two billion years ago,<br />

followed by a stable maturity briefly interrupted by a<br />

mid-life crisis 800 to 500 million years ago. This new,<br />

surprising timeline of the geomagnetic field raises<br />

important questions about the relationship between<br />

Earth’s interior and the magnetic field that it produces.<br />

To reconstruct the history of Earth’s magnetic field,<br />

Evans analyzed rocks that record the magnetic field’s<br />

direction. Like tiny compasses, minerals in iron-rich<br />

rocks orient their magnetic directions to align with the<br />

Earth’s magnetic field during rock formation. These<br />

patterns can then be read to indicate magnetic north<br />

when the rocks formed. Evans and Driscoll focused on<br />

the period from 2.0 to 0.9 billion years ago, from which<br />

data has been historically scarce and difficult to interpret<br />

due to the scarcity of old, unaltered magnetic rocks. But<br />

years of research by Evans and other paleomagnetic<br />

experts has produced a global database of paleomagnetic<br />

data from this period extensive enough to produce<br />

robust conclusions.<br />

After analyzing this new historical record, Evans and<br />

Driscoll were particularly surprised by the similarity in<br />

the behavior of the magnetic field from two billion to<br />

900 million years ago compared to the last 500 million<br />

years. Aside from two brief periods of volatile behavior—<br />

the adolescent and mid-life crisis periods—the behavior<br />

of the magnetic field, and specifically the frequency of<br />

superchrons, or periods of at least 10 million years with<br />

one dominant polarity, appear to have been similar for<br />

most of the past two billion years.<br />

This stability is surprising because Evans and Driscoll<br />

believe that the Earth’s core underwent a dramatic<br />

change during this time period, which they expect<br />

would have had a lasting impact on the behavior of the<br />

magnetic field. Previous research suggests that the core<br />

was entirely liquid until about 700 million years ago,<br />

when the nucleus of a solid iron core formed and began<br />

to grow. The slow solidification of the solid inner core<br />

is expected to influence fluid motion and magnetic field<br />

generation in the outer core due to the additional heat<br />

release and changing geometry.<br />

Evans and Driscoll believe these changes may have<br />

facilitated the recovery from the mid-life crisis, but they<br />

expected that the crisis would have had lingering effects.<br />

“What surprised us was that the field before and after the<br />

mid-life crisis was so similar, because we think that the<br />

physical generation mechanism of the Earth’s magnetic<br />

field would be very different with and without a solid<br />

inner core,” Evans said.<br />

Researchers like Driscoll will need to consider how this<br />

newly confirmed stability informs their models of the<br />

evolution of the core and magnetic field. “The elephant<br />

in the room is, when did the inner core first start<br />

solidifying?” said Driscoll. “Is there an observational<br />

signature of the event?”<br />

Meanwhile, Evans hopes to better understand what<br />

was going on during the two paleomagentic crises “How<br />

was the magnetic field different in those times of crisis?<br />

That’s the more exciting frontier for me,” Evans said.<br />


►An iron-rich sedimentary rock, which can preserve the Earth’s<br />

magnetic field from the distant past.<br />

8 Yale Scientific Magazine April 2016 www.yalescientific.org

environmental science<br />

NEWS<br />


Disproportionate release of green-house gases<br />



►A small pond in Connecticut releases disproportionate<br />

amounts of carbon from terrestrial surroundings into the<br />

atmosphere.<br />

During mid-February, a warm breeze rushes by instead of<br />

an expected snow flurry. It should be no surprise that human<br />

activities—such as the burning of fossil fuels and deforestation—are<br />

partially to blame for increasingly warm<br />

temperatures. Yet, less well-known are the natural sources<br />

of atmospheric carbon present before human activities led<br />

to climate change. Could ponds be a natural contributor to<br />

greenhouse gas emissions?<br />

Researchers at Yale University recently found that very<br />

small ponds emit a disproportionate amount of the greenhouse<br />

gases carbon dioxide (CO 2<br />

) and methane (CH 4<br />

) relative<br />

to their surface area. Yet, since small ponds are hard<br />

to view by satellite, they have traditionally been left out of<br />

carbon flux, or movement, calculations. This new study<br />

demonstrates the importance of accounting for these small<br />

bodies of inland water in the global carbon budget.<br />

The global carbon cycle describes the movement of carbon<br />

through the Earth’s atmosphere, oceans, land, and rock.<br />

Carbon “sinks,” which include terrestrial plants and oceans,<br />

remove and store carbon from the atmosphere. They play an<br />

important role as atmospheric carbon, primarily existing as<br />

CO 2<br />

and CH 4<br />

, can be problematic for the environment. Both<br />

gases—especially CH 4<br />

, a gas 20 times potent than CO 2<br />

—are<br />

key greenhouse gases, and heat up the Earth’s atmosphere.<br />

Oceans are good at reducing atmospheric carbon, but not<br />

all bodies of water are. Ponds and lakes, for instance, are<br />

known to increase atmospheric carbon levels. Because small<br />

bodies of inland water are often situated under canopies of<br />

vegetation in concave positions on the landscape, they collect<br />

falling leaf litter and other sources of terrestrial carbon<br />

that is then degraded by microbes, yielding CO 2<br />

.<br />

Despite its importance, the carbon flux from small ponds<br />

has been overlooked in past estimates of greenhouse gas<br />

budgets because the global distribution of very small ponds<br />

is hard to map. Very small ponds are difficult to see by satellite<br />

imaging. Furthermore, two other variables for carbon<br />

flux calculations, carbon concentrations and gas transfer velocity,<br />

are difficult to estimate accurately for small ponds.<br />

In the study, researchers Meredith Holgerson and Peter<br />

Raymond compiled direct measurements of CO 2<br />

and CH 4<br />

concentrations from 427 lakes and ponds around the world.<br />

After clustering these lakes and ponds into seven categories<br />

by size, Holgerson found that CO 2<br />

and CH 4<br />

concentrations<br />

were disproportionately high in the smallest ponds.<br />

This observation may be explained by the high perimeter<br />

to surface area ratio and shallow depth of small ponds. These<br />

allow small ponds to receive more terrestrial carbon and release<br />

more CO 2<br />

. Furthermore, because small ponds are often<br />

shallow, mixing between layers of the pond is more rapid.<br />

Thus, CH 4<br />

, produced in the oxygen-deficient sediments at<br />

the bottom of ponds, escapes into the atmosphere before it<br />

can be converted into other compounds.<br />

Surprisingly, though very small ponds only make up 8.6<br />

percent of lakes and ponds by area globally, Holgerson discovered<br />

that they are responsible for 15.1 percent of inland<br />

water CO 2<br />

emissions and 40.6 percent of inland water CH 4<br />

emissions. “While…each pond is small, they collectively<br />

made a large contribution to the global carbon cycle in inland<br />

waters,” said Meredith Holgerson, a Yale doctoral student.<br />

The impact of very small ponds shows the necessity to include<br />

them in future estimates of carbon flux from inland<br />

waters. As expected, there are a few hurdles along the way.<br />

“We need more direct measurements of carbon dioxide<br />

from inland waters. Current methods using extrapolation<br />

are pretty accurate for many, but not all, water bodies,” Holgerson<br />

said. Mapping the global distribution of these small<br />

ponds will also pose a challenge. By replacing traditional<br />

satellite methods by light detection and ranging data (Li-<br />

DAR)—which works by airborne laser scanning—researchers<br />

may be able to provide better estimates.<br />

“This sort of effort to get global inland water [greenhouse<br />

gas] emissions is fairly new. These tiny systems have not<br />

been part of any other efforts,” said Peter Raymond, Yale<br />

professor of ecosystem ecology.<br />

www.yalescientific.org<br />

April 2016<br />

Yale Scientific Magazine<br />


NEWS<br />

medicine<br />


A new approach to sepsis prediction<br />


You have just finished watching a great movie on Netflix.<br />

However, the night is still young, and you want to<br />

watch another movie. But where to start? There are so<br />

many different genres…so many different options. Fortunately,<br />

Netflix has analyzed your viewing history and<br />

immediately recommends a movie catered to your tastes.<br />

Your movie experience continues uninterrupted, as you<br />

settle in for another “Quirky British Comedy” film.<br />

Such predictive techniques are very common in the<br />

fields of finance and social media. Now, according to a<br />

recent study conducted by researchers at the Yale School<br />

of Medicine, these methods may soon be applicable in the<br />

hospital. Yale professor Andrew Taylor and his team have<br />

developed a series of generalizable analytic methods that<br />

can be used to make predictions for patient care. As a<br />

proof-of-concept, they focused on sepsis, which is a potentially<br />

fatal bacterial infection. As nearly half of all hospital<br />

deaths are related to sepsis, the importance of early<br />

sepsis prediction is clear.<br />

“The medical field is five or ten years behind other fields<br />

as far as being able to make machine-learning based, real-time<br />

predictions,” said Taylor, lead author of the study.<br />

“Considering that Facebook tailors ads to users based on<br />

previous data, one has to ask why the medical field is not<br />

doing something similar to improve patient outcomes.”<br />

In order to predict sepsis risk, physicians commonly<br />

use clinical decision rules: a simple scoring system developed<br />

through prior studies. Based on score values, different<br />

decisions are recommended. For example, if a patient<br />

presents with a high heart rate, swelling in one leg, and<br />

shortness of breath, clinical decision scores would recommend<br />

further testing for the patient. “The problem<br />

with this is poor generalizability, because each patient<br />

is so unique and these scoring systems are developed in<br />

hospital systems with very different patient populations,”<br />

said Kennedy Hall, co-author of the study. “We decided to<br />

develop a general approach, rather than a subset of variables,<br />

that could be used to predict sepsis and other diseases.”<br />

The specific machine learning based approach used in<br />

this study was Random Forest modeling. In this model,<br />

random subsets of patient variables are used to create a<br />

proverbial “forest of trees.” The trees then essentially vote<br />

on whether an outcome—for instance, sepsis—will happen<br />

based on the available data. “The beauty of this approach<br />

is that, instead of creating a model with four or<br />

five variables, we can now use thousands of variables that<br />

already exist in the medical health records,” Taylor said.<br />

Upon comparison with existing prediction models, including<br />

several clinical decision rules, Random Forest<br />

significantly outperformed the competition. Translated<br />

to real numbers, this means that annually, hundreds of<br />

additional patients in a hospital can be correctly identified<br />

for risk of death from sepsis.<br />

The research team envisions a future where hospitals<br />

use analytic methods that are adaptable to their own patient<br />

populations. This is a new way of thinking. Instead<br />

of developing one specific model, the team proposes that<br />

autonomous methods should be developed and shared so<br />

that hospitals can learn from their own patients and improve<br />

care.<br />

Unfortunately, these predictive techniques have not<br />

trickled into the mainstream yet. There is still some reluctance<br />

in the medical field to accept the “black box”<br />

approach of using machines instead of people. However,<br />

Taylor and Hall believe that these models should aid,<br />

rather than supplant, physician judgment. “We must give<br />

up some power to the more versatile and accurate ‘black<br />

box’ approach,” Hall said.<br />

Now having established a proof-of-concept, Taylor and<br />

Hall are looking for new ways to optimize their approach<br />

and extend it to other patient care domains. “The next<br />

step is implementation in the hospital,” Taylor said. “In<br />

the next few years, we hope to move from theory to practice<br />

and make real differences in patients’ lives.”<br />


►The Random Forest model developed by Taylor and his team<br />

can predict the risk of sepsis, commonly called blood poisoning.<br />

These are unaffected, healthy red blood cells.<br />

10 Yale Scientific Magazine April 2016 www.yalescientific.org

genetics<br />

NEWS<br />


An evolutionary tree for tumor cells<br />


Sometimes, when scientists apply the knowledge and<br />

methods of one discipline to another, surprising and novel<br />

discoveries can manifest. Questions such as “How did<br />

each case of cancer come to be?” may benefit from an additional<br />

perspective, complementing that of a traditional<br />

oncologist. A team led by Yale University professor Jeff<br />

Townsend utilized techniques from the fields of evolutionary<br />

biology and bioinformatics to explore this question<br />

through a new lens. Earlier in 2016, their research<br />

was published in the Proceedings of the National Academy<br />

of Sciences, providing new evidence that the development<br />

of cancer in an individual’s body can be thought of<br />

as an evolutionary process. This insight has the potential<br />

to inform the development of more efficient treatments<br />

for cancer.<br />

One of the reasons why cancers are so difficult to understand<br />

and treat is that they can change rapidly within a patient’s<br />

body, garnering new mutations and properties over<br />

time. Metastasis—the spread and migration of cancerous<br />

cells to various parts of the body—is perhaps the most<br />

critical determining factor for the survival rate of cancer<br />

patients. In order to better understand how these types of<br />

www.yalescientific.org<br />


►Jeffrey Townsend, Zi-Ming Zhao, and Stephen Gaffney are<br />

three of the authors of the paper published in February 2016.<br />

They work at the Townsend Lab, a Yale biostatistics lab.<br />

cells develop, Zi-Ming Zhao, postdoctoral associate and<br />

lead author of the paper, worked with her fellow scientists<br />

to unravel the connections between different cancer cell<br />

lineages in a patient’s body.<br />

Townsend and collaborators in Yale’s genetics, pathology,<br />

and pharmacology departments had generated an<br />

immense wealth of genome sequencing data from cancer<br />

patients. The team constructed evolutionary trees to pinpoint<br />

when known cancer-linked mutations are likely to<br />

occur. They found that some mutations occurring in the<br />

early stages of cancer development—near the root of the<br />

evolutionary tree—can promote metastasis later on. Over<br />

time, different series of mutations can lead to a variety of<br />

paths along which cancer evolves and diversifies within a<br />

patient.<br />

“These evolutionary techniques were traditionally applied<br />

to multiple species, but we applied them to multiple<br />

independent tumor tissues that all evolved from normal<br />

tissue,” Townsend said. Previous studies had compared<br />

normal tissues to primary tumors, but Zhao said that<br />

the Yale-based study took this analysis one step further<br />

by comparing the various metastatic tissue lineages. The<br />

team also was able to find subtle distinctions between tissues<br />

from the same tumor, by comparing sequencing data<br />

from a myriad of genes. The team’s success further underscores<br />

the heterogeneity of cancer cells.<br />

Applying an evolutionary lens to oncology not only enhances<br />

scientists’ understanding of how cancers come to<br />

be and how they develop, but also improves how treatments<br />

for actual patients are developed and administered.<br />

“It is not just an evolutionary model or cancer data; it is<br />

also about how a patient can be treated, [and] how we can<br />

maintain their lives,” Zhao said.<br />

Townsend emphasized that the ability to predict the<br />

likely ways that cancer evolves in the body would be a<br />

powerful tool for researchers. Knowing which early-stage<br />

mutations drive metastasis would allow scientists to target<br />

these key factors from the beginning. “There is diversity<br />

within the disease, and we have to think very carefully and<br />

adaptively about how we treat patients with cancer, so as<br />

to make sure we target every part of the cancer that [they]<br />

have,” Townsend added.<br />

Looking forward, the Townsend lab will build upon<br />

their research by looking at “longitudinal data,” tracking<br />

the development of cancers in patients from their diagnosis<br />

onward. As it stands, this study is helping to set a precedent<br />

in the realm of basic research: it is a testament to the<br />

power of an interdisciplinary approach and the utility of<br />

massive data sets.<br />

April 2016<br />

Yale Scientific Magazine<br />


alumni<br />


ESSAY<br />



a neglected modality in promoting and preserving populations of endangered species<br />

►BY HYUN JIN KIM from stuyvesant high school<br />

It is not uncommon to see advertisements warning people<br />

about DNA tests that might determine cancer risk, or popular<br />

hype around websites like ancestry.com or dnamydog.com.<br />

While humans have invested huge amounts of time and money<br />

into exploring their heritage—and that of their puppies—<br />

surprisingly little work has been done on much more pressing<br />

concerns: the genetics of species on the brink of extinction.<br />

While it is relatively common knowledge that many animal<br />

and plant species have been threatened by destructive human<br />

activities, it is less common knowledge that genetics play an<br />

important role in determining risk of extinction. Conservation<br />

geneticists have deployed their knowledge of genetics to<br />

suggest that genetic factors frequently observed in small populations<br />

contribute to extinction risk in endangered species.<br />

In particular, inbreeding reduces the viability of reproduction<br />

and survival rates, while minimal genetic diversity tends to diminish<br />

resilience to respond to environmental change.<br />

Although several scientists sounded the call many years ago<br />

for increased attention to genetics among endangered species,<br />

few mainstream biologists have seriously supported their concern.<br />

In 1988 the evolutionary biologist Russell Lande, currently<br />

at Imperial College London, argued that demographic<br />

factors such as “social structure, life history variation caused<br />

by environmental fluctuation, dispersal in spatially heterogeneous<br />

environments, and local extinction and colonization,”<br />

are not the only concerns worth considering in endangered<br />

populations. However, his plea to instead pay attention to<br />

genetic factors went largely unheeded. Many scientists at the<br />

time considered inbreeding a trivial issue since they believed<br />

purging, or getting rid of harmful mutations, could be a highly<br />

effective solution to inbreeding. Since then, however, even<br />

though other scientists have used models to demonstrate that<br />

the effects of purging are small, scientists and activists continue<br />

to underestimate the impact of inbreeding on population<br />

viability. According to Richard Frankham’s research in 2003,<br />

demography was still regarded as the major determinant in<br />

the fate of endangered species as late as the 1990’s. Even today,<br />

Lande’s original critique is still largely valid due to many scientists’<br />

conviction that factors such as the spread of disease, catastrophes,<br />

or even cultural value associated with specific species<br />

are the controlling factors for extinction.<br />

Though the extinction of vertebrates on islands has traditionally<br />

been associated with non-genetic factors, two probable<br />

causes are actually inbreeding and loss of genetic diversity.<br />

Due to the relatively small size of most islands, endemic island<br />

populations generally possess less genetic diversity than analogous<br />

mainland populations because the size of these populations<br />

rarely experiences major changes. For example, over a<br />

century ago, two or three koalas from the Strzelecki Ranges<br />

in Australia were relocated to nearby French Island. Unfortunately<br />

their offspring ultimately exhibited increased male sterility.<br />

As illustrated by these koalas, indigenous populations<br />

are susceptible to inbreeding decreasing genetic diversity.<br />

Thus, recent efforts to initiate recovery programs for endangered<br />

species will be drastically less effective if genetic factors<br />

are not taken into account. For example, when scientists crossbred<br />

greater prairie chickens in Illinois with unrelated chickens<br />

from other states and allowed them to mate freely within<br />

a big population, the inbreeding that habitat restorations had<br />

been unable to eliminate stopped. The chickens became fertile<br />

and more eggs were successfully brought to term.<br />

Genetic factors, particularly inbreeding and reduction in<br />

genetic diversity, ultimately control the fate of small or fragmented<br />

populations with limited gene flow. Not only do these<br />

factors increase the risk of extinction, but they also limit evolution<br />

that might help organisms cope with environmental<br />

change, thereby undercutting long-term survival. Already a<br />

complicated algorithm, conservation biology must consider<br />

the genetic management of fragmented populations, so that<br />

this under-addressed issue doesn’t thwart our best intentions<br />

in ways we least expect. Should we want future generations<br />

to enjoy many of the endangered species around today, inefficient<br />

genetic management of threatened species compels us<br />

to take action.<br />

12 Yale Scientific Magazine April 2016 www.yalescientific.org

cell biology<br />

FOCUS<br />

ROBOT<br />

friend<br />

or<br />

foe?<br />

by Kendrick<br />

Umstattd<br />

art by<br />

Aydin<br />

Akyol<br />

www.yalescientific.org<br />

April 2016<br />

Yale Scientific Magazine<br />


From R2-D2 and<br />

C-3PO in Star<br />

Wars to Baymax<br />

in Big Hero 6, we are captivated<br />

by robots. They can<br />

be simultaneously entertaining,<br />

endearing, and inspiring.<br />

As films that incorporate these<br />

concepts seem to draw sizeable audiences,<br />

there must be something<br />

about these mechanical imitations of<br />

ourselves that resonates with us. Are we<br />

simply enamored with the technological<br />

complexity of these fantastical creations or<br />

is there something more? “Robots are ‘evocative<br />

objects’ that force us to focus on what is<br />

important while bringing research into the<br />

context of the real world,” said Brian Scassellati<br />

of Yale’s Social Robotics Lab. When robots<br />

are artificially intelligent—thus possessing<br />

the ability to perform humanlike tasks<br />

and “think” at a higher level—they capture<br />

our attention. At times, they even steal our<br />

hearts in films like Wall-E, but as these machines<br />

become more and more advanced, a<br />

new question has come up: Could these intelligent<br />

machines also steal our jobs?<br />

Cracking the code on AI<br />

The term “artificial intelligence” (AI) can<br />

be a controversial buzzword. It is a field that<br />

seamlessly integrates engineering, computer<br />

science, and cognitive science, among other<br />

disciplines, and it has many connotations<br />

that are both warranted and unwarranted.<br />

What likely comes to mind when someone<br />

mentions this field is advanced robots,<br />

whether they be benign like C-3PO, or dangerous<br />

like the Terminator. Consequently, it<br />

may come as a surprise that artificial intelligence<br />

had a less glamorous start.<br />

One of the pioneers of the field of artificial<br />

intelligence was Alan Turing, a British<br />

mathematician. In order to crack the Nazis’<br />

encoded messages with Joan Clarke and other<br />

fellow Bletchley Park code-breakers, Turing<br />

developed the bombe, a machine that<br />

worked to analyze—and break—the enemy’s<br />

codes. Although this machine looked<br />

from the outside like a set of stacked panels<br />

with spinning wheels, it was, in fact, one of<br />

the earliest artificially intelligent machines.<br />

What made the machine artificially intelligent<br />

was its ability to perform processes<br />

typically carried out by humans, specifically<br />

code-breaking. Although artificial intelligence<br />

can be incorporated into devices running<br />

the gamut from advanced robotics to<br />

your smartphone, the essence of artificial<br />

intelligence is the capacity of something to<br />

mimic human mental processes.<br />

The unifying foundation of artificial intelligence—its<br />

ability to mimic the way people<br />

solve problems—is the root of why we find<br />

it so interesting: Through the development<br />

of this field, we can learn more about ourselves<br />

and how our brains function. Electrical<br />

wires are the robot’s version of neurons,<br />

and the electric current is the equivalent of<br />

the electrical impulses that spark activity<br />

in the human brain. When a coder presses<br />

“run” on a program that powers an AI machine,<br />

she essentially breathes life into it.<br />

Debug before you run<br />

As artificially intelligent machines become<br />

more advanced, they raise increasingly<br />

tricky questions, for instance questions<br />

about whether these advanced machines will<br />

replace a large proportion of human workers<br />

in the near future. Although humans can<br />

be better understood through robotics, and<br />

although human mental functioning serves<br />

as the inspiration for artificial intelligence,<br />

there is an essential difference between humans<br />

and robots: The latter doesn’t require<br />

sleep, pay, or a break from work.<br />

In a world where the full potential of artificial<br />

intelligence is achieved, robots would<br />

be capable of learning, socializing, and<br />

thinking in the same advanced way as humans.<br />

With the rising momentum in regard<br />

to the development of this field, some worry<br />

that robots will soon be viewed as efficient,<br />

cheaper replacements for human workers.<br />

This is where the controversy within this<br />

field arises.<br />

Wendell Wallach, author of the book A<br />

Dangerous Master: How to Keep Technology<br />

from Slipping Beyond Our Control, provided<br />

some insight. Although full robotic replication<br />

of human functioning is something that<br />

likely will not occur in the foreseeable future,<br />

robots are currently capable of carrying<br />

out repetitive tasks involved in some jobs.<br />

“I would love AI to inspect every pipeline<br />

and bolt in a ship: mind-numbing jobs that<br />

need to be done, so to me those are the great<br />

breakthroughs,” said Wallach. At the same<br />

time, these are jobs that provide for people’s<br />

14 Yale Scientific Magazine April 2016 www.yalescientific.org

technology<br />

FOCUS<br />

livelihoods, allowing them to support themselves<br />

and their families. Workers fear that<br />

their employers may only think of increased<br />

profit when deciding between human and<br />

robot worker, creating a society in which human<br />

workers are left destitute.<br />

When asked about the best course of action,<br />

Wallach said that the process of artificial<br />

intelligence development is not one that<br />

can easily be slowed. Instead, a better course<br />

of action would be to develop policies aimed<br />

at adapting to the process more quickly. At<br />

the moment, this issue is primarily being<br />

discussed by individuals active in technology<br />

fields. In order for policy regulating the<br />

use of artificially intelligent machines to be<br />

made, our politicians must be engaged in<br />

conversation about this issue. Once everyone<br />

joins in, we can work together to address<br />

these concerns and adapt to the technological<br />

advancements. One way of accomplishing<br />

this is to realize what human workers<br />

bring to their jobs other than productivity.<br />

People bring compassion, dedication, and<br />

care for their work that cannot be provided<br />

by a robot worker.<br />

As the development of AI continues, we<br />

should seek to use artificially intelligent machines<br />

alongside human workers, allowing<br />

robots to, for example, retrieve dangerous<br />

materials that may harm a human. As a society,<br />

however, it is essential that we draw the<br />

line between the replacement of workers for<br />

robots in jobs that put human lives at risk<br />

and those that, although at times tedious, are<br />

what provide for individuals’ livelihoods.<br />

Programming the future<br />

the development of artificial intelligence, but<br />

when the right team is assembled—a team<br />

that understands the complicated, multidisciplinary<br />

nature of this field—the pros far<br />

outweigh the cons.<br />

At the Yale Social Robotics Lab, robots<br />

are helping children learn. One particularly<br />

helpful robot serves as an aid in teaching<br />

English to native Spanish speakers in grades<br />

K-12. The children, who are often nervous<br />

about making translation errors in front of<br />

their teachers, feel much more at ease with<br />

the robot. Their mistakes can be tracked, allowing<br />

for tailored instruction for each individual<br />

student. Over the course of five sessions<br />

with the robot, it was found that all of<br />

the children improved their English-speaking<br />

abilities.<br />

The positive impact of artificial intelligence<br />

is not limited to education. It spans<br />

from daily productivity to healthcare.<br />

Whenever you ask Siri a question, you are<br />

using artificial intelligence for convenience.<br />

Beyond daily applications, artificial intelligence<br />

is revolutionizing the way medicine<br />

is practiced. Online information banks like<br />

Modernizing Medicine help doctors diagnose<br />

symptoms that do not obviously point<br />

to a specific illness. It is worth emphasizing,<br />

however, that the doctor is still the one who<br />

makes the final call in these situations because<br />

her training and expertise is invaluable<br />

to her patients receiving proper treatment.<br />

The capabilities of artificial intelligence<br />

can be more than important; they are also<br />

exciting. Go, a complicated board game, was<br />

thought to be too complex for a machine to<br />

master, but Google has recently proven this<br />

assumption wrong. In March, Google’s AlphaGo<br />

program went head-to-head with the<br />

world’s best Go player, and reigned victorious<br />

in a best-of-five match. This is an exciting<br />

advancement in the development of<br />

artificial intelligence, demonstrating another<br />

boundary that has been broken down by<br />

skilled engineers and coders.<br />

A call to action<br />

Going forward, the field dedicated to developing<br />

artificially intelligent machines<br />

does not simply need people who are skilled<br />

coders and engineers. It needs ethically and<br />

politically literate individuals cognizant of<br />

the impact of their work. Having multiple<br />

perspectives will spark essential conversations<br />

about how to adjust to the changing<br />

world in which we live.<br />

Just as we, as a society, have adjusted to numerous<br />

prior technological advancements,<br />

we can learn how to make advanced robotics<br />

work for us without allowing them to work<br />

in our place. With each new technological<br />

advancement, there are people who stand on<br />

both sides of issues. But these concerns are<br />

no reason to abandon a field that possesses<br />

so many benefits for society. Instead, as<br />

we have before, we must adjust to this new<br />

advancement. In a field with never-ending<br />

changes and development, our best path forward<br />

is one that embraces a quote from Alan<br />

Turing: “We can only see a short distance<br />

ahead, but we can see plenty there that needs<br />

to be done.”<br />

If one were only to consider the dangers of<br />

the development of artificial intelligence, it<br />

would appear that the best course of action is<br />

to discontinue this field of research altogether.<br />

But where would we be if we had chosen<br />

this path over the course of past technological<br />

advancements? What if we had never<br />

developed the telephone or the computer?<br />

What if we had abandoned investment in advanced<br />

modes of transportation because of<br />

potential risks? With any new advancement<br />

comes risks and concerns. Fortunately, at the<br />

end of the day, it is us who decide whether or<br />

not robots will ever be serious competitors<br />

for jobs. Further, one should not view the<br />

field of robotics as one of doom and gloom.<br />

As with anything, there are pros and cons to<br />



KENDRICK UMSTATTD is a freshman Electrical Engineering and Computer<br />

Science major in Berkeley College. She is a Copy Editor for the Yale Scientific<br />

Magazine and works as a research assistant in Yale’s Social Robotics Lab.<br />

THE AUTHOR WOULD LIKE TO THANK Wendell Wallach for his time and<br />

perspective on this issue. She would also like to thank Brian Scassellati for<br />

his enthusiasm and for the work his lab does to advance robotics so as to<br />

improve people’s quality of life.<br />


Wallach, Wendell. A Dangerous Master: How to Keep Technology from<br />

Slipping beyond Our Control. New York, NY: Basic Books, 2015.<br />

www.yalescientific.org<br />

April 2016<br />

Yale Scientific Magazine<br />


FOCUS<br />

genetics<br />


FISHY<br />

about<br />

estrogen<br />

Zebrafish model offers new<br />

perspective on autism<br />

by Aviva Abusch//art by Sharon Welch<br />

If your childhood home had a television<br />

set, you can probably tell me how to get<br />

to Sesame Street. Those who outgrew<br />

the show before 2015 befriended the original<br />

cast of characters—muppets like Big<br />

Bird, Ernie and Bert—and remember songs<br />

from “Elmo’s World.” We missed out on<br />

meeting the newest muppet, Julia, and singing<br />

“The Amazing Song”—two important<br />

additions. Julia is the first autistic character<br />

on Sesame Street, and “The Amazing Song”<br />

teaches young viewers about their friends<br />

living with autism spectrum disorder.<br />

What “The Amazing Song” does not<br />

touch on is that autism spectrum disorder<br />

(ASD) can be a devastating diagnosis. While<br />

oftentimes, autistic individuals are amazing<br />

and go on to live full and meaningful lives,<br />

many are severely limited by symptoms<br />

whose origin and cure are both unknown.<br />

One in 68 children today is diagnosed with<br />

the disorder (one in 42 boys and one in<br />

189 girls)—each child at a different level of<br />

functionality—and despite its constant rise<br />

in prevalence and its enormous impact on<br />

those affected, ASD is still not completely<br />

understood, and there are still no effective<br />

pharmacological treatments for its core<br />

symptoms. Today, through research and<br />

clinical work, professionals have accumulated<br />

a lengthy list of symptoms and genetic<br />

indicators and designed several effective<br />

psychotherapeutic techniques. Awareness,<br />

as in the case of Sesame Street, continues to<br />

spread. Yet for most researchers, clinicians<br />

and families, this is still barely scratching the<br />

surface.<br />

Professors Ellen Hoffman and Antonio<br />

Giraldez at the Yale School of Medicine are<br />

a couple of those researchers. In their recent<br />

project, Hoffman, Giraldez and their teams<br />

combined methods of gene discovery and<br />

drug discovery to uncover more information<br />

about autism. Using zebrafish as model<br />

organisms, the team discovered that compounds<br />

resembling estrogen reverse the<br />

behavioral manifestations of an autism-like<br />

genetic abnormality in mutant organisms.<br />

Though many scientific hurdles stand between<br />

current findings and human applicability,<br />

estrogen may hold promising answers<br />

for future ASD research and treatment.<br />

A is for Autism<br />

To quote the wisdom of Sesame Street’s<br />

Abby Cadabby, having autism means certain<br />

kids’ “brains just work a little differently,”<br />

and some things are harder for kids with<br />

ASD. Abby is right; at its most severe, autism<br />

eliminates communication and social motivation,<br />

and it creates debilitating resistance<br />

to change. Specific symptoms range from<br />

loss of language and seizures to repetitive behaviors<br />

and self-injury, and those with ASD<br />

may face difficulties managing aggression,<br />

getting enough sleep, and recognizing social<br />

cues. Because the severity varies along a<br />

spectrum, some children are high functioning<br />

and display few symptoms, while others<br />

are incapable of participating in a typically<br />

functioning social environment. Even playing<br />

outside can be challenging for a child<br />

with ASD who experiences hypersensitivity<br />

to ordinary stimuli, like lights and sounds.<br />

Despite the significance of ASD symptoms,<br />

the ability to even receive an autism<br />

diagnosis is new; autism was first described<br />

in 1943 and was only officially recognized<br />

in 1980. Extensive research on ASD did not<br />

kick off until the 1990s, and though several<br />

genes have been implicated in the disorder,<br />

it is still unclear how disruptions in these<br />

genes lead to the clinical manifestations of<br />

autism. Giraldez, a Yale professor of genetics<br />

and a father himself, was devastated to<br />

see how the social repercussions of autism<br />

could sever a crucial bond between parent<br />

and child. Together with Hoffman—an assistant<br />

professor at the Yale Child Study<br />

Center—he and the rest of their team sought<br />

to gain information about the molecular<br />

mishaps that lead to ASD by studying an<br />

16 Yale Scientific Magazine April 2016 www.yalescientific.org

genetics<br />

FOCUS<br />

unlikely model organism: the zebrafish.<br />

Making a splash in autism research<br />

Hoffman and Giraldez began their project<br />

in 2008 by collaborating with Matt State,<br />

who had identified a specific gene of interest:<br />

CNTNAP2. A mutation in CNTNAP2—a<br />

gene that had been identified three years<br />

prior—is strongly linked to ASD symptoms<br />

in a small Amish population in Pennsylvania.<br />

Using molecular scissors known as zinc<br />

finger nucleases, the Yale team disrupted<br />

the same gene in zebrafish and observed the<br />

outcome in their offspring. They found that<br />

zebrafish larvae that were double mutants<br />

for CNTNAP2 were far more active at night<br />

compared to their normal counterparts.<br />

This finding, or—as Giraldez calls it—the<br />

“behavioral fingerprint,” was only the start<br />

of their process. “If you observe behavioral<br />

changes in the mutants, you then try to find<br />

a drug that will reverse that deficit,” Giraldez<br />

said.<br />

The team did just that. After taking<br />

the behavioral fingerprint of the mutant<br />

zebrafish larvae, they collaborated with<br />

Jason Rihel at the University of London to<br />

compare the observed behavior to that of<br />

both normal embryos as well as embryos<br />

that had been exposed to hundreds of<br />

different drugs. Because of the rapid rate<br />

of fertilization in zebrafish, it is possible<br />

to obtain hundreds of larvae and expose<br />

large numbers of them to each drug. The<br />

larvae can then be grouped by symptom,<br />

enabling the researchers to categorize both<br />

the drugs that cause normal embryos to<br />

express mutant traits as well as those that<br />

cause the mutant embryos to display normal<br />

behaviors. Another zebrafish perk is that<br />

they are transparent, allowing researchers to<br />

observe early stages of neural development<br />

and early behavior in embryos.<br />

To their surprise, Hoffman, Giraldez and<br />

their colleagues discovered that compounds<br />

resembling estrogen, a female hormone,<br />

limited the expression of abnormal behaviors<br />

in mutant fish. Because autism occurs<br />

about four times more often in males than<br />

females, these results were particularly intriguing.<br />

“From a genetic standpoint, it<br />

looks like there is some type of female protective<br />

factor,” Hoffman said. Giraldez also<br />

expressed enthusiasm about this possibility.<br />

“This data could tell us about how the physiological<br />

differences we see every day could<br />

be influencing things that are not as simple<br />

as what’s on the outside,” he said.<br />

But despite both researchers’ initial excitement,<br />

their immediate goal is not to develop<br />

autism drug therapy. They are investigating<br />

the impacted circuitry, and their utilization<br />

of drug research is actually a method to<br />

uncover common mechanisms underlying<br />

ASD. “We primarily are trying to understand<br />

what genes that are associated with<br />

autism risk do,” Hoffman said. “How come<br />

when these genes are disrupted they have<br />

the effects that they do?” This problem runs<br />

much deeper and is one they have just begun<br />

to tackle.<br />

Big fish in an enormous pond<br />

Although mutations in CNTNAP2 have<br />

been linked to ASD and epilepsy within a<br />

specific ethnic group, Hoffman emphasized<br />

the universality of their research. “Identifying<br />

these very rare mutations of big effect<br />

can teach us something important about the<br />

biological mechanisms underlying autism,”<br />

Hoffman said. “We think that whatever<br />

mechanisms we identify through this research<br />

will be crucial to future understanding<br />

of more common forms of autism.”<br />

Their next steps are numerous. As they<br />

move into further research, many more<br />

factors—and organisms—come into play.<br />

Hoffman emphasized that studies involving<br />

rodent models of ASD are an important<br />

next step. “Using a simple model system is a<br />

good way to get at mechanisms that underlie<br />

a disorder,” Hoffman said. “But we are still<br />

looking to identify the underlying circuits<br />

that are disrupted in mutant fish. Further<br />

studies in mice are essential before this work<br />

can be applied to human patients.”<br />

Fishing for future projects<br />


►The image shows a wild-type zebrafish<br />

brain at four days post-fertilization with the<br />

embryos stained for certain neurons.<br />

Through this project, Giraldez garnered<br />

valuable information about the realm of research<br />

possibilities. “In an area such as autism,<br />

which most people think can only be<br />

studied in humans, important discoveries<br />

can come from the most unassuming areas<br />

of a laboratory,” Giraldez said. Rather than<br />

constraining project ideas to the obvious,<br />

Giraldez encourages researchers to think<br />

beyond what was once feasible.<br />

Currently, there are a vast number<br />

of opportunities for creative scientific<br />

exploration, both within and outside the<br />

field of autism research. And by taking on<br />

outside-the-box projects—whether that<br />

means generating mutations in zebrafish<br />

or adding a new character on a beloved TV<br />

series—we have the potential to create a<br />

powerful impact.<br />



AVIVA ABUSCH is a sophomore Cognitive Science major in Pierson College,<br />

specifically studying the neurological, psychological and societal effects of<br />

autism spectrum disorder. She is the current <strong>YSM</strong> Production Manager and<br />

a regular writer for both the magazine and The Scope.<br />

THE AUTHOR WOULD LIKE TO THANK Professors Ellen Hoffman and<br />

Antonio Giraldez for their time and insights in discussing their work.<br />


Hoffman, E. et al. (2016). Estrogens Suppress a Behavioral Phenotype<br />

in Zebrafish Mutants of the Autism Risk Gene, CNTNAP2. Neuron, 89(4),<br />

725-733.<br />

www.yalescientific.org<br />

April 2016<br />

Yale Scientific Magazine<br />


FOCUS<br />

environmental science<br />


MARKET<br />




by Kathryn Ward<br />

art by Ashlyn Oakes<br />

NATURE<br />

Sustainability transcends disciplines, and<br />

the question of how to protect natural<br />

resources from pillaging by profit-hungry<br />

corporations and governments alike spans<br />

technological, economic, and political fields.<br />

Efficiency measures and water filters have<br />

their place, but key to implementing any measure<br />

is an analysis of where action is required,<br />

who needs it, and how it is to be fulfilled.<br />

Currently, such cost-benefit analysis is<br />

alarmingly one-sided. The cost of a water purification<br />

station built on the Quinnipiac River<br />

can be estimated. The benefits, however, are<br />

ethereal, and attempts to reflect these benefits<br />

in dollar values that policymakers best understand<br />

lack much of their true value. Emerging<br />

methodologies for natural resource pricing<br />

promise future cost-benefit analyses that account<br />

for current externalities, providing the<br />

hope for a more systematically sustainable future.<br />

Researchers responding to the call for new<br />

methods are forging new collaborations in<br />

search of unique approaches to the problem.<br />

Yale’s own Eli Fenichel, assistant professor in<br />

the Yale School of Forestry & Environmental<br />

Science, is one such researcher. In his paper,<br />

“Measuring the value of groundwater and other<br />

forms of natural capital,” he works to craft<br />

an interdisciplinary approach to evaluating<br />

nature’s price. The research team specifically<br />

examined Kansas’ High Plains Aquifer and<br />

constructed a model of pricing the groundwater.<br />

The aquifer supports billions of dollars<br />

in agricultural revenue, and the group’s<br />

results warned of losses in groundwater value<br />

unaddressed by policymakers. Groundwater<br />

supports 40 percent of the world’s food production,<br />

but it is a resource past researchers<br />

have struggled to value. In fact, the 2014 UN<br />

Inclusive Wealth Report specifically targets<br />

groundwater valuation as an area of necessary<br />

improvement. Ultimately, accurate valuation<br />

of natural resources allows for their inclusion<br />

within cost-benefit scenarios through economic<br />

comparison.<br />

Markets and resources<br />

Resources are most easily valued by the<br />

products extracted from them. It is far simpler<br />

to assign a price tag to a mango tree based on<br />

the value of mangos sold than to calculate its<br />

effect on adjacent crops or take into account<br />

its anti-erosion value. Yet, the assignment of<br />

value to natural resources based purely on<br />

productive results fails to ensure long-term<br />

success.<br />

A four-decade-old National Bureau of Economic<br />

Research report describes the gap<br />

between economic and environmental accounting,<br />

claiming that the conventional final-product-based<br />

approach “gives incorrect<br />

indications of changes in welfare…because it<br />

fails to allow for the disamenities associated<br />

with industrial growth, particularly pollution

environmental science<br />

FOCUS<br />

of air and water.” The old call for new methodology<br />

has become increasingly urgent, as<br />

modern institutions need better evaluative<br />

measures to quantify the plethora of sustainability<br />

measures taking root across the world.<br />

World organizations and a call for progress<br />

In particular, the World Bank has criticized<br />

GDP’s role as the foremost index of national<br />

economic success. Instead, it has sought to<br />

implement new forms of wealth accounting<br />

that takes into consideration natural resource<br />

holdings. National Capital Accounting (NCA)<br />

credits long-term development of a portfolio<br />

of assets beyond just industrial products, including<br />

natural, human, and social capital.<br />

NCA has risen in public awareness, most notably<br />

when the UN adopted it with its Statistical<br />

Commission of the System for Environmental<br />

and Economic Accounts in 2012 for<br />

application to extraction-intensive industries<br />

like minerals, timber, and fisheries.<br />

However, the methodology of NCA is far<br />

from set, and one of the key goals of the World<br />

Bank’s NCA project was to develop an accurate<br />

ecosystem accounting methodology<br />

while building support for its use. NCA can<br />

provide a common language for sustainability<br />

measures between policymakers, scientists,<br />

and economists by placing everything in the<br />

same units—in this case, dollars.<br />

Groundwater as capital<br />

Professor Eli Fenichel’s groundwater study<br />

sought out just that: an accurate price on<br />

groundwater that takes into account its natural<br />

impacts. Erin Haacker, a geologist at Michigan<br />

State, had done previous research on the<br />

Kansas High Plains Aquifer and contributed<br />

technical expertise to the research that ultimately<br />

yielded groundbreaking results.<br />

Groundwater contributes value to ecosystems<br />

in a myriad of ways, from natural purification<br />

to soil stabilization to agricultural<br />

watering. The National Research Council describes<br />

groundwater’s value as “determined<br />

jointly by the interaction of geologic/hydrologic<br />

factors and economic factors,” and an<br />

analysis of these factors revealed a potential<br />

crisis in the making.<br />

To begin valuing the groundwater, the researchers<br />

first had to quantify the water. The<br />

team defined the stock of groundwater as a<br />

measure of rock saturation by aquifer volume<br />

and looked for volume changes over a ten-year<br />

period under one surface acre. Over the time<br />

period, they found that the water under an average<br />

acre fell by about a foot, or by two-fifths<br />

of a percent annually. Then, they used NCA<br />

to estimate the value of that lost groundwater.<br />

The research team estimated through<br />

their model that Kansas lost $110 million of<br />

groundwater value over a ten-year period.<br />

Given the importance of data in driving policy<br />

decisions related to investment, Fenichel<br />

called for a portfolio management decision-making<br />

process that included such natural<br />

capital losses alongside agricultural gains<br />

so that policymakers had the data to evaluate<br />

future measures. “A lack of data is an increasingly<br />

poor excuse for not taking externalities<br />

into account,” Fenichel said, using the economic<br />

term for costs not taken into account<br />

by the market system. The natural and social<br />

sciences often struggle to overlap in scope,<br />

but mathematics can serve to connect them.<br />

“Mathematics [is] the language of interdisciplinary<br />

research,” Fenichel said. He argued<br />

that quantitative models can bridge gaps between<br />

fields to better describe important systems.<br />

Paths forward<br />

The results of Fenichel’s research lend weight<br />

to calls such as the World Bank’s for wealth<br />

accounting that includes natural resources.<br />

Renowned environmental economist Pavan<br />

Sukhdev argues that putting a price on natural<br />

resources makes states aware of their ecological<br />

resources, and that decision-makers<br />

currently lack the weighing measures to make<br />

good decisions. “Economics is mere weaponry,”<br />

Sukhdev said in a recent post.<br />

The UN is particularly eager to apply better<br />

models to decisions over competing land uses,<br />

and NCA has immense promise for developing<br />

and developed countries alike. Countries<br />

have incentive to apply accurate cost-benefit<br />

analysis to counteract possible resource depletion,<br />

and Fenichel argued that Kansas should<br />

offset losses in groundwater with equal investments,<br />

whether in water storage, education, or<br />

a myriad of other options. Developing countries,<br />

however, often struggle to make decisions<br />

over land use, such as decisions over hydropower,<br />

in areas rich in biodiversity. NCA<br />

can better quantify decisions to maximize<br />

economic growth while minimizing tradeoffs<br />

such as flood protection and other ecosystem<br />

services. In the case of the Kansas High Plains<br />

Aquifer, the research done by Fenichel and his<br />

colleagues provides data for lawmakers to pursue<br />

sustainable alternative investments as necessary<br />

for their continued wellbeing, instead<br />

of an expensive and unrelated consideration.<br />

Ecosystems are incredibly complex scientific<br />

systems. Politics are amazingly difficult<br />

to navigate. Economics is frustratingly imprecise.<br />

The combination of the three presents extreme<br />

difficulty, but to protect natural systems,<br />

models to bring factors into the same units are<br />

essential to yield beneficial decisions. Natural<br />

capital accounting and other attempts to price<br />

natural resources formerly outside of market<br />

systems offer the promise of including previously<br />

unseen consequences into the discussion<br />

as momentum builds for environmental<br />

protection.<br />



KATHRYN WARD is a sophomore applied mathematics major in Timothy<br />

Dwight College fascinated by the interplay between technology, economics,<br />

and politics in the rapidly evolving energy industry. She writes additionally for<br />

the Yale Globalist, serves as the editor-in-chief of the Yale Pawprint, is a Yale<br />

Energy Club board member, and leads School of Engineering tours.<br />

THE AUTHOR WOULD LIKE TO THANK Professor Fenichel for taking the time<br />

to interview.<br />


Fenichel, Abbott, Bayham, Boone, Haacker, and Pfeiffer. “Measuring the value<br />

of groundwater and other forms of natural capital.” Proceedings of the National<br />

Academy of Sciences of the United States of America. Vol. 113 No. 9 (Dec 2015).<br />

www.yalescientific.org<br />

April 2016<br />

Yale Scientific Magazine<br />



applied physics<br />

FOCUS<br />

Reach in your pocket and you’ll<br />

pull out a little piece of magic.<br />

That rectangular box is able to<br />

connect people continents apart, access<br />

the world’s libraries, and deliver breaking<br />

news as it happens. Smartphones<br />

owe their success to the explosive<br />

growth in computing technologies—today,<br />

engineers can fit billions of transistors<br />

onto the tip of your finger.<br />

Even more ‘magical’ technologies<br />

are possible, and scientists believe that<br />

quantum computers hold the key to the<br />

next wave of technological even more<br />

“magical” technologies. In a major<br />

breakthrough, researchers at the Yale<br />

Quantum Institute have now developed<br />

the world’s first quantum information<br />

chip. Professor of electrical engineering<br />

and physics Hong Tang and post-doctoral<br />

researcher Carsten Schuck report<br />

in a recent Nature Communications<br />

paper that they have successfully put<br />

the essential components of quantum<br />

information processes on silicon-based<br />

chip. This scalable technology could<br />

make theoretical quantum computation<br />

a reality, unleashing tremendous<br />

advances and producing answers that<br />

classical computers can never hope to<br />

attain.<br />

While quantum computing has been<br />

done in the past, it has always required<br />

room-sized setups. Now, with the power<br />

of microfabrication, the team of Yale<br />

researchers is hoping to make quantum<br />

computers even smaller than ever before<br />

through fundamentally changing<br />

how they are made.<br />

Where no computer has gone before<br />

Quantum computers are a breed apart<br />

from the ordinary devices we are familiar<br />

with. Many people imagine them to<br />

be quite like our personal desktops, just<br />

much faster and smarter. Perhaps quantum<br />

computers could help us predict<br />

next month’s weather, or even discover<br />

better drugs, many think. However,<br />

these are tasks for supercomputers—<br />

powerful classical computers that already<br />

sit in remote facilities around the<br />

world. Quantum computers instead<br />

promise to rise to new challenges, like<br />

cracking currently unbreakable cryptographic<br />

codes by rapid factorizing<br />

large prime numbers and advancing our<br />

understanding of the physical world by<br />

performing complex simulations.<br />

Quantum computers differ from classical<br />

computers in one key way: Instead<br />

of having regular bits, they have<br />

quantum bits, or “qubits.” Bits are very<br />

simple units of data; they are either a 1<br />

(‘on’) or a 0 (‘off ’). However, computer<br />

engineers have designed logical systems<br />

that harnesses our ability to manipulate<br />

them at mind-boggling speeds. Today’s<br />

top supercomputers can manipulate a<br />

thousand trillion operations per second,<br />

simulating everything from highend<br />

video production to the evolution<br />

of our universe. Quantum bits have<br />

three states instead of two: on, off, and<br />

a third position that is, strangely, both<br />

on and off. This third state is unique<br />

to quantum technologies, and it has<br />

far-reaching implications for our understanding<br />

of the world.<br />

It is a misconception to say that quantum<br />

computers are simply ‘better’ than<br />

classical computers. Although quantum<br />

computers use fewer qubits when<br />

compared to a classical computer’s bits<br />

in performing a calculation, it will be<br />

a long time before quantum computers<br />

can attain the power of our home<br />

desktop, and much longer before they<br />

reach the power of supercomputers.<br />

The power of the quantum computer<br />

lies in its ability to perform tasks that<br />

classical computers cannot do; because<br />


►Though the quantum chip is microscopic,<br />

the devices needed to maintain it are not.<br />

For the quantum chip to work properly, it<br />

must be cooled to only a few Kelvin, using<br />

the vacuum devices shown here. This is still<br />

an improvement over older setups.<br />

of the unique physics involved with a<br />

qubit, it is able to solve problems in a<br />

completely different way.<br />

The famously misattributed Einstein<br />

quote comes to mind: “If you judge a<br />

fish by its ability to climb a tree, it will<br />

live its whole life believing that it is stupid.”<br />

Our classical supercomputers have<br />

scaled the highest of trees, allowing us<br />

to see the islands of knowledge that lie<br />

across the ocean. But it will take the<br />

quantum computer’s ability to swim to<br />

finally get there.<br />

The challenge of qubits<br />

But scientists still have a dilemma.<br />

Although the qubit has been created in<br />

laboratories, it is difficult to mass produce<br />

them. Classical computers have<br />

flourished because scientists mastered<br />

the art of silicon transistors. Bits are<br />

merely the idea that computers are built<br />

on; transistors hold the actual, physical<br />

representation of the bit. Likewise, qubits<br />

have been developed in fantastic algorithms,<br />

yet there has not been a truly<br />

scalable physical representation of the<br />

qubit. There are great ideas—Robert<br />

Schoekopf, director of the Yale Quantum<br />

Institute, was the inventor of the<br />

superconducting qubit—but a consensus<br />

on which direction to take has yet<br />

to be made.<br />

The major problem today seems to<br />

be one of scale. Although scientists<br />

can create qubits in the lab, they require<br />

temperatures close to absolute<br />

zeroalong withgiant room-sized tables<br />

of optical instruments. And that is only<br />

for a few qubits.<br />

“If we ever want to do something<br />

that goes to a large scale, something<br />

that classical computers cannot do,<br />

you need to have scalable technologies,”<br />

said Carsten Schuck, lead author<br />

of the paper on the quantum chip. His<br />

new development at the Yale Quantum<br />

Institute—the scalable quantum chip—<br />

tackles exactly that problem. With it,<br />

scientists can integrate as many qubits<br />

as needed onto a single chip.<br />

Building a quantum chip from scratch<br />

Schuck’s interest is with photonic<br />

qubits—that is, qubits that operate using<br />

the quantum nature of light. Those<br />

quantum properties have been demonstrated<br />

again and again in the labora-<br />

www.yalescientific.org<br />

April 2016<br />

Yale Scientific Magazine<br />


FOCUS<br />

applied physics<br />

tory, but it has been a challenge to scale<br />

them. Photons, or particles of light, have<br />

the benefit of being relatively resistant to<br />

environmental changes; they do not lose<br />

their quantum properties if the temperature<br />

changes microscopically, unlike the<br />

more sensitive superconducting circuit.<br />

To create a scalable quantum chip, scientists<br />

need to integrate three distinct<br />

components on a single chip: one to produce<br />

photonic qubits, one to propagate<br />

those photons, and the last to measure<br />

the photons’ final states. Any quantum<br />

computer would need all three components<br />

working together in harmony.<br />

That need for harmony led to the partnership<br />

between Schuck, a physicist intrigued<br />

by entangled photon pairs, and<br />

Tang, whose primary appointment at<br />

Yale is with the Department of Electrical<br />

Engineering. As experts in their respective<br />

fields, Tang and Schuck collaborated<br />

to do quantum information on a scalable<br />

platform.<br />

Tang and Schuck’s breakthrough with<br />

the silicon chip comes from merging<br />

their expertise to solve the propagation<br />

and detection problems. Tang’s expertise<br />

in microfabrication created waveguides<br />

for the photons that were only one millionth<br />

of a meter across. The configuration<br />

of these waveguides allows for operations<br />

to be performed on qubits, much<br />

like how transistors allow for operations<br />

to be performed on regular bits. These<br />

waveguides are unique and were fundamental<br />

to the function of the quantum<br />

chip.<br />

Meanwhile, Schuck’s experience allowed<br />

for the integration of quantum<br />

technologies onto this silicon chip The<br />

Superconducting Single Photon Detector,<br />

or SSPD, is a device specially engineered<br />

so it has the ability to detect the<br />

single photons that travel in the waveguides.<br />

In fact, because this detector behaves<br />

according to quantum laws rather<br />

than classical laws, it sees much more information<br />

than regular detectors. If the<br />

regular detector were a black-and-white<br />

camera, the SSPD would be akin to a color<br />

camera, collecting much richer information<br />

if used properly.<br />

Tang and Schuck have already verified<br />

a fundamental quantum interference effect<br />

using their detectors, proving that<br />

their chip is able to convey quantum information.<br />

Showing this to be true was<br />

no easy task. “The generation of this<br />

photon qubit is a random process, so<br />

we only have a probability of generating<br />

[it],” Tang said. In order to demonstrate<br />

the quantum interference effect, the<br />

team had to generate a very large number<br />

of photon pairs to guarantee that<br />

enough photonic qubits were produced.<br />

The successful generation and detection<br />

of qubits by their quantum chip opens<br />

new doors for research, emboldening<br />

colleagues to take the Yale team’s current<br />

chip and make further modifications to<br />

the waveguides, creating more complex<br />

algorithms and increasing the chip’s reliability.<br />

Dawn of the quantum age<br />

There is much work to be done. For<br />

now, Tang and Schuck have only integrated<br />

two components—the propagation<br />

and detection elements—onto<br />

a single silicon chip. The source of the<br />

photonic qubits is still generated by a<br />

laser some distance away, and for good<br />

reason. Placed any closer, the laser<br />

would heat up the SSPD, ruining any detection<br />

of the photonic qubits. “If we can<br />

put the source on the chip as well—that’s<br />

basically the dream of where we want to<br />

go,” Schuck said.<br />

Will we be seeing this chip adopted by<br />

microprocessor giants like Intel or IBM?<br />

It is hard to see that in the near future.<br />

There are still too many questions to be<br />

answered about how the chip will scale<br />

and whether the technology will pan out.<br />

Going from purely scientific discoveries<br />

to a working business model is a huge<br />

step that carries much risk. Still, the researchers<br />

are optimistic. “If [research]<br />


►In the future, quantum chips could look as<br />

symmetric as the standard green chips in our<br />

computer today. The only difference: instead<br />

of electrons zooming around, entangled<br />

pairs of photons will do the complex calculations<br />

needed to create a better world.<br />

continues like that, there may be interest<br />

in the future,” Schuck said. “But at the<br />

moment, there is still more to show.”<br />

These Yale researchers not only developed<br />

a new technology—they created a<br />

new paradigm for developing quantum<br />

technologies. The emphasis on balancing<br />

scalability with reliability is crucial<br />

for developing the field of quantum<br />

computing. Not so long ago, classical<br />

computers faced the same problem, with<br />

giant room-sized vacuum tubes providing<br />

the only way to manipulate bits. The<br />

invention of the transistor allowed for<br />

the steady improvement of computers,<br />

and today, they are tiny pockets of magic<br />

that we have accepted into our lives.<br />

Perhaps one day in the not-so-distant<br />

future, we will look back and marvel at<br />

how, once again, a new wave of technology<br />

has transformed our daily lives.<br />



CHUNYANG DING is a freshman in Saybrook College and a prospective Physics<br />

major. He currently serves as Operations Manager for the Yale Scientific and<br />

works in Professor Geha’s lab studying satellite galaxies.<br />

THE AUTHOR WOULD LIKE TO THANK Dr. Carsten Schuck, Professor Hong<br />

Tang, and Professor Liang Jiang for their time and enthusiasm in discussing their<br />

research.<br />


Devoret, M H, and R J Schoelkopf. 2013. “Superconducting Circuits for<br />

Quantum Information: An Outlook.” Science 339 (6124): 1169–74. http://science.<br />

sciencemag.org/content/339/6124/1169.abstract.<br />

22 Yale Scientific Magazine April 2016 www.yalescientific.org

public health<br />

FOCUS<br />

Sugar: the lonely soul’s best friend and<br />

the dieter’s worst nightmare. It is an<br />

undeniable truth that when we crave<br />

a snack, we tend to reach for those forbidden<br />

sweets, not the asparagus sitting in<br />

the fridge. So, what is it about sugar that<br />

gives it such power over people? A study<br />

recently published in Nature Neuroscience<br />

may have found the answer: sugar<br />

cravings have little to do with sweetness<br />

and everything to do with calories.<br />

The brain on sugar<br />

Researchers at Yale’s John B. Pierce<br />

Laboratory performed a series of experiments<br />

to look into brain activity related to<br />

sugar intake. It has long been known that<br />

the striatum, a subcortical region of the<br />

brain, is involved in reward circuitry, but<br />

how this circuitry functioned in response<br />

to sugar remained unclear. The researchers<br />

discovered that separate regions of the<br />

striatum controlled response to the pleasurable<br />

(sweetness) and nutritional (calorie<br />

content) aspects of sugar. Specifically,<br />

the ventral striatum controls the response<br />

to sweetness, and the dorsal striatum mediates<br />

the response to calories.<br />

Working with mice, researchers observed<br />

that ventral striatum activity increased<br />

when mice licked a sweet solution,<br />

even if they were given infusions<br />

of calorie-free sugar. Conversely, dorsal<br />

striatum activity increased when the mice<br />

were given infusions of ordinary sugar,<br />

even if the mice were licking a bitter solution.<br />

These experiments helped demonstrate<br />

that the ventral striatum is activated<br />

in response to sweetness, while the<br />

dorsal striatum is activated in response to<br />

calories.<br />

www.yalescientific.org<br />

Activation of these regions in turn determined<br />

the feeding behavior of the<br />

mice. In a second set of experiments, the<br />

researchers taught the mice that licking<br />

the bitter solution would result in an infusion<br />

of sugar. Mice with a functioning<br />

dorsal striatum opted to bite the bullet<br />

and lick the bitter solution so long as the<br />

infusions they received had high concentrations<br />

of sugar; however, when the<br />

researchers inhibited the neuronal signaling<br />

in this brain region, the mice licked<br />

the bitter solution less frequently. In other<br />

words, if the circuitry controlling the<br />

response to calories did not work, the<br />

mice did not feel compelled to consume<br />

more.<br />

The researchers then wanted to find out<br />

which of the responses – pleasure or nutrition<br />

– would win out if the mice had to<br />

make a choice. They did this with an elegant<br />

experiment, teaching the mice that<br />

licking the bitter solution would provide<br />

an infusion of ordinary sugar while<br />

licking the sweet solution would<br />

provide an infusion<br />

of non-nutritive<br />

sugar. Unsurprisingly,<br />

mice in which researchers inhibited the<br />

dorsal striatum chose to lick the sweet<br />

solution. What was interesting was that<br />

mice with proper dorsal striatum function<br />

preferred licking the bitter solution,<br />

indicating that mice will sacrifice sweetness<br />

for calorie content.<br />

To provide further evidence for their<br />

model of brain function, the team used<br />

optogenetic techniques to turn the dorsal<br />

and ventral striatum regions on and off.<br />

In optogenetics, scientists engineer a target<br />

gene so that it is only expressed when<br />

a light-sensitive ion channel detects particular<br />

wavelengths of light that researchers<br />

shine on it. When the researchers artificially<br />

activated the dorsal striatum, the<br />

mice were willing to lick the bitter solution<br />

despite not actually receiving any<br />

sugar infusions. This demonstrated that<br />

artificial activation can substitute for the<br />

effects of caloric sugar intake when the<br />

mice are faced with unpleasant tastes.<br />

Interestingly, artificial stimulation<br />

of the ventral striatum did<br />

not have the same effect,<br />

indicating that cues from<br />

the calorie pathway<br />

carry more weight in<br />

the brain than those<br />

from the sweetness<br />

pathway.<br />

April 2016<br />

Yale Scientific Magazine<br />


FOCUS<br />

public health<br />


►Rats provided with high-calorie human<br />

foods eat more than they would if only provided<br />

with rat chow and quickly become obese.<br />

To eat or not to eat<br />

The results of this study provide a<br />

wealth of information on specific neuroscience,<br />

but the question that remains is<br />

how all the mechanistic jargon translates<br />

to actual thoughts and behaviors. When<br />

we head to the snack drawer, we do not<br />

pause to ask ourselves, “What is my ventral<br />

striatum telling me to eat? What is my<br />

dorsal striatum telling me to eat?” The reality<br />

is that this process occurs completely<br />

subconsciously.<br />

In the midst of a culture obsessed with<br />

diet fads, a nutritional philosophy called<br />

“intuitive eating” has arisen. Originating<br />

in the 1970s, intuitive eating emphasizes<br />

the importance of simply trusting the<br />

mind and body to be attuned to our nutritional<br />

needs. Numerous studies have<br />

demonstrated that intuitive eating promotes<br />

maintenance of a healthy weight<br />

and weight loss in those with prior problems<br />

overeating. In light of the results of<br />

this study, this philosophy seems even<br />

more appropriate. “The brain knows we<br />

are getting low in reserves,” said Ivan de<br />

Araujo, associate professor of psychiatry<br />

and cellular and molecular physiology<br />

and senior author of the study. “You<br />

should use the fact that the brain is getting<br />

rewarded as a guide for what you<br />

should eat.” When we are hungry, our<br />

brain signals the need to take in calories<br />

regardless of sweetness, and when we are<br />

not particularly hungry, the desire for<br />

something sweet wins out.<br />

If we accept the fact that the brain unconsciously<br />

regulates our intake, the next<br />

thing to consider is how activity in the<br />

striatum translates to the act of eating.<br />

The brain may be aware that the body<br />

needs a specific thing to eat, but what signal<br />

from the brain tells us to get up and<br />

walk to the refrigerator? The researchers<br />

in this study propose a model where the<br />

striatum is functionally linked to a region<br />

of the brain called the premotor reticular<br />

formation, which is located in the<br />

brainstem and signals the spinal cord to<br />

produce motion. In other words, we are<br />

never conscious of what is going on in the<br />

brain, but the brain knows what it is doing<br />

when it decides to lead us to the snack<br />

drawer. “We believe that calories go into<br />

parts of the brain without recruiting the<br />

conscious cognitive areas, a path [neuroscientists]<br />

call ‘the low road.’ …Our voluntary<br />

urges are kind of illusions created<br />

by feedback from something you actually<br />

did,” said de Araujo.<br />

The caloric sweet spot<br />

The understanding of the sugar pathways<br />

in the brain has implications beyond<br />

individual behavior, including informing<br />

the food industry as well as psychologists<br />

studying compulsive eating. One wellknown<br />

study is that of the Pima Indians.<br />

The tribe in Arizona has the highest obesity<br />

and type 2 diabetes rates in the United<br />

States, even though the tribe in Mexico<br />

faces few of these issues. Not surprisingly,<br />

the Pima Indians have become the poster<br />

children for the mismatch between genetics<br />

and the food environment. In Mexico,<br />

the Pima Indians experience food scarcity<br />

and eat what we think of as a “paleo” diet,<br />

whereas in Arizona, they eat an American<br />

diet replete with processed sugars.<br />

The body only needs a certain number<br />

of calories, and the reward circuitry in<br />

the brain likely developed at a time when<br />

food was scarce in order to allow for the<br />

consumption of as much energy as possible.<br />

However, the overwhelming quantity<br />

of sugars in the American diet takes advantage<br />

of this system and throws off the<br />

balance between sweetness and calories<br />

in the brain. “The brain somehow figured<br />

out that…the ability to survive using energy<br />

is more important than the opportunity<br />

to sense pleasure out of sweetness,”<br />

de Araujo said. “Our food environment is<br />

a mismatch for that system.”<br />

Given the nature of the food environment<br />

and the fact that much of the blame<br />

lies with the processed food industry, it<br />

is now more important than ever for the<br />

industry to focus on creating foods that<br />

remedy the issue. Dr. de Araujo and his<br />

team believe that it would be possible to<br />

reach a point where the inputs from the<br />

calorie pathway and the sweetness pathway<br />

perfectly counterbalance one another–a<br />

“caloric sweet spot,” if you will.<br />

What if the food industry could use this<br />

information to manufacture foods that<br />

can satisfy both our need for energy and<br />

our desire for sugar? Perhaps it would be<br />

possible to recreate our food environment<br />

with the knowledge that calories<br />

and sweetness are separate entities, and<br />

to one day reduce the incidence of obesity,<br />

compulsive eating, diabetes and other<br />

sugar-related problems facing society.<br />

Wouldn’t that be sweet?<br />



JESSICA SCHMERLER is a junior in Jonathan Edwards College majoring in<br />

molecular, cellular & developmental biology, neurobiology track. She is a member<br />

of the Yale Journalism Initiative, a writer for Scientific American MIND, a writer and<br />

editor to several on-campus publications and a member of Yale Cheerleading.<br />

THE AUTHOR WOULD LIKE TO THANK Dr. de Araujo for his time and<br />

enthusiasm about his research.<br />


Johnson, P.M. & Kenny, P.J. (2010). Dopamine D2 receptors in addiction-like<br />

reward dysfunction and compulsive eating in obese rats. Nature Neuroscience,<br />

13, pp635-641.(2015): 16012-16017.<br />

24 Yale Scientific Magazine April 2016 www.yalescientific.org

cell biology<br />



Bacteria in motion<br />


The smooth green surface of a rock sits just below a<br />

pond’s surface. Its deceptively uniform green coating is<br />

teeming with life: algae, bacteria, and other microorganisms.<br />

They all depend on sunlight for energy and are<br />

constantly competing with each other for better access<br />

to light. While some microbes are immobile, stuck on<br />

to the rock in their original positions, others are mobile<br />

and move around on the rock’s surface in response<br />

to light. In the past, little was known about how bacteria<br />

perform phototaxis, motion in response to light. Recently<br />

however, researchers discovered that cyanobacteria,<br />

a subset of bacteria able to perform photosynthesis,<br />

act like tiny eyes, able to focus light internally and move<br />

towards its source.<br />

Synechocystis, the species of cyanobacteria used in<br />

this study, is spherically shaped. As a result, it can focus<br />

light to the back side of the cell, so that the region of the<br />

cell farthest from the light source is the brightest. The<br />

bacteria respond to this brightness, moving away from<br />

that side and advancing towards the light. Synechocystis<br />

move using pili, hair like strands that coat the surface of<br />

the cell and attach to nearby surfaces, dragging the cell<br />

along in a jerking motion, in this case towards a light<br />

source.<br />

This study shows that the mechanism of phototaxis<br />

is completely different than that of chemotaxis, cellular<br />

motion in response to a chemical stimulus. Cells<br />

that perform chemotaxis have long protrusions called<br />

flagella that rotate in liquid like propellers and direct the<br />

cell’s motion. They move towards or away from chemicals<br />

using a combination of continuous motion and tumbles,<br />

stops with random changes in direction. With each<br />

change in direction, the cell’s goal is to move towards a<br />

more desirable chemical concentration. When it reaches<br />

a beneficial concentration, the bacterium continues on<br />

its course, but once it becomes adjusted to the new concentration,<br />

tumbling returns.<br />

The cells detect light using a method similar to that of<br />

the human eye: the side of the cell receiving light acts<br />

like a convex lens, bringing all of the angles of a light<br />

source together into a focal point. Within a human eye,<br />

this focal point aligns with the retina, so the eye can<br />

communicate with the brain. In cyanobacteria, the focal<br />

point is at the back of the cell, where light is intensified<br />

and the pili shrink, moving the cell closer to the light<br />

source. This mechanism of direct detection is unprecedented.<br />

“This is something that was not actually known<br />

in bacteria before,” said Conrad Mullineaux, microbiology<br />

professor and a lead scientist of the project.<br />

Before now, phototaxis baffled microbiologists because<br />

of the small size of bacteria. Cyanobacteria are tiny, only<br />

a mere 0.0003 centimeters in diameter on average. When<br />

Mullineaux first learned that individual cyanobacteria<br />

cells could detect light, he was shocked. “I thought it was<br />

all completely impossible,” Mullineaux said. For many<br />

months, Mullineaux formulated new theories about<br />

the mechanism of phototaxis, but they were repeatedly<br />

proven wrong within the lab. Eventually, there was a<br />

breakthrough when Nils Schuergers, a graduate student<br />

working on the project, shone light from the side of a<br />

microscope at the cells. Small, focused spots of light appeared<br />

on the sides of the cells opposite from the light<br />

source. “As soon as we saw it, it was completely obvious,”<br />

Mullineaux said. “The cell must act as a lens.”<br />

This new insight into how light travels through bacterial<br />

cells may be relevant to more than phototaxis. It<br />

raises a host of new questions about the amount of light<br />

cells are capable of absorbing. And since sunlight provides<br />

the energy for photosynthesis, a cell’s ability to absorb<br />

light controls how much carbon it can take in from<br />

the atmosphere.<br />


►Cyanobacteria, as pictured above, have different layers<br />

around their outer surfaces that affect how light is absorbed<br />

by cells. The light is focused on the back of the cell, where it is<br />

detected by photoreceptors.<br />

www.yalescientific.org<br />

April 2016<br />

Yale Scientific Magazine<br />



astronomy<br />


Looking beyond the Milky Way<br />


Have you ever wondered about galaxies far, far away? If you<br />

have, then you are not alone.<br />

An international team of scientists recently discovered hundreds<br />

of hidden, nearby galaxies while surveying the region behind<br />

the southern Milky Way. Using the Parkes radio telescope in<br />

Australia, which is equipped with an innovative receiver to detect<br />

hydrogen radio waves, the team uncovered 883 galaxies. A third<br />

of these galaxies had never been detected before. Until now, the<br />

Milky Way’s dense stars and dust have prevented scientists from<br />

mapping this region of extragalactic sky beyond our galaxy.<br />

Patricia Henning, an astrophysics professor at the University<br />

of New Mexico, helped lead the project. The obscured region of<br />

extragalactic sky she surveyed is commonly called the Zone of<br />

Avoidance. “That’s a wonderful, old-fashioned name that dates<br />

back to before astronomers even knew that the spiral nebulae that<br />

we saw were actually external galaxies,” Henning said. “Astronomers<br />

noticed that fuzzy patches of spiral nebulae avoided this big<br />

band around the sky. Now we understand that those nebulae are<br />

actually external galaxies, and that it’s just difficult to see those<br />

galaxies in visible light through our own Milky Way.”<br />

“The combination of many stars and obscuring dust means<br />

that the light from galaxies behind the Milky Way really can’t<br />

penetrate our galaxy and get to our optical telescopes,” Henning<br />

explained. Instead of attempting to detect light, the research team<br />

used the radio signature of hydrogen gas, which is present in<br />

many galaxies, including ours. Hydrogen gas emits a wavelength<br />

that is much longer than optical wavelengths and larger than obscuring<br />

dust. Since this wavelength easily passes through the dust<br />

of our Milky Way, Henning and other researchers could detect<br />

the hydrogen signatures from these hidden galaxies using the<br />

Parkes radio telescope.<br />

The results of this survey technique were highly interesting to<br />

astrophysicists. By locating the galaxies, researchers could see<br />

mass concentrations associated with structures above and below<br />

the galactic plane, the region which contains most of the luminous<br />

objects in the galaxy (to visualize our galactic plane, imagine<br />

our galaxy’s disc “edge-on,” or lying on a two-dimensional plane).<br />

Some mass concentrations from the survey matched up with our<br />

previous map of the Milky Way’s planar region, but many clumps<br />

of mass were new. In particular, researchers found mass associated<br />

with many new galaxies in a famous region called the Great<br />

Attractor.<br />

The Great Attractor has been a mystery to scientists for decades.<br />

We have known for a hundred years that galaxies move apart due<br />

to the expansion of the universe, but galaxies also have additional<br />

velocities due to gravitational motions. In regions of high galactic<br />

mass, gravity is stronger, creating motion due to gravitational<br />

perturbations between neighboring galaxies. Scientists have understood<br />

since the 1980s that galaxies feel the gravitational pull<br />

of other galaxy clusters. They associate these galactic movements<br />

with areas of high mass by comparing galactic flow fields with<br />

galaxy maps. The Great Attractor is puzzling to scientists, however,<br />

because the discovered galaxies in this region do not account<br />

for the gravitational attraction it generates. Researchers speculate<br />

that the region must contain a large amount of mass unassociated<br />

with previously discovered galaxies. “We were looking for regular<br />

galaxies that would help account for this mass,” Henning said.<br />

Henning pioneered this project’s specific survey technique<br />

back in 1987, but until this project, it could not be put into effect<br />

because of a lack of sophisticated technology. Even when the<br />

project first began, the Parkes telescope was the only telescope<br />

with a receiver advanced enough to detect hydrogen waves.<br />

“We’ve known since the 1980s that it is plausible to do what our<br />

team has accomplished,” Henning said. “The receiver that’s on the<br />

Parkes Telescope was absolutely fundamental to our being able to<br />

conduct this survey.”<br />

The team was comprised of scientists from the United States,<br />

the Netherlands, South Africa, and Australia, but collaboration<br />

was never an issue. “Like-minded and like-interested people<br />

came together to use the Parkes telescope,” Henning explained.<br />

“We collaborated sometimes via Skype. You can do international<br />

collaborations pretty easily these days.”<br />

Henning is leading a new team in a project in Puerto Rico,<br />

using another telescope to map the Zone of Avoidance in areas<br />

north of where it was mapped using the Parkes telescope. Since<br />

this telescope is highly sensitive, researchers will be able to detect<br />

objects that are very small and farther away. Henning expects to<br />

find many more galaxies than were previously discovered in the<br />

southern Zone of Avoidance.<br />


►The Parkes Radio Telescope in Parkes, Australia.<br />

26 Yale Scientific Magazine April 2016 www.yalescientific.org

materials science<br />



A future possibility?<br />



►A globe containing plasma that extends from an electrode in<br />

the middle of the globe to an insulating outer sphere. Plasma is<br />

the state of matter used in magnetron sputtering.<br />

Imagine pressing a button that converts the window in your<br />

living room into a flat screen TV. This technology may seem<br />

straight out of a science fiction movie, but it could be possible<br />

in the near future. Kenneth Chau, an associate professor at the<br />

University of British Columbia, is heading a group of researchers<br />

who recently discovered a method to both enhance the amount<br />

of light coming through a window and allow the glass to conduct<br />

electricity, facilitating the creation of novel technologies.<br />

Previously metal was incorporated into some windows to improve<br />

their ability to reflect heat, but these researchers were the<br />

first to coat the window’s surface with metal. Unexpectedly, these<br />

thin sheets of metal not only gave glass the ability to conduct<br />

electricity but also increased the amount of light capable of passing<br />

through it.<br />

“It’s been known for quite a while that you could put glass on<br />

metal to make metal more transparent, but people have never<br />

put metal on top of glass to make glass more transparent,” said<br />

Loïc Markley, a collaborator on the project, in an interview with<br />

Science Daily.<br />

It may seem counter-intuitive that glass becomes more transparent<br />

when coated with metal, a highly reflective material.<br />

However, the laws of electromagnetism support the researchers’<br />

empirical findings. Plastic is a dielectric substance, meaning that<br />

it is a poor conductor of electricity. According to Maxwell’s equations,<br />

the path for light to pass through a thin glass layer becomes<br />

shorter when a layer of metal is added. Since light’s path is shortened,<br />

the metal-dielectric bilayer is more transparent than the dielectric<br />

layer alone.<br />

At the University of British Columbia, researchers aimed to<br />

prove this theory by coating sheets of glass with thin membranes<br />

of silver. Magnetron sputtering, a process used to deposit materials<br />

onto a surface, was used to apply a thin layer of silver onto the<br />

silicon nitride (glass) membrane. In magnetron sputtering, positively<br />

charged ions of plasma—a state of matter including electrically<br />

conductive gases— are attracted to a target substance of<br />

opposite charge. This attraction results in extremely thin films of<br />

plasma on the target substance, only eight to fifteen nanometers<br />

thick— a length that is over 5000 times thinner than a sheet of<br />

paper.<br />

The researchers conducted trials to test whether certain configurations<br />

of silver-coated glass transmitted more light. An optical<br />

spectrometer, a tool that measures light intensity versus<br />

wavelength, was used in each trial to measure the glass’s ability<br />

to transmit light. After many trials, professor Chau and his<br />

team were able to increase light transmission by up to six percent,<br />

but only in the blue portion of the visible light spectrum.<br />

There was no difference in transmission between glass coated by<br />

metal on one side and glass coated on both sides. According to<br />

the research team, light transmission could be further increased<br />

if scientists could create even thinner, perfectly flat films of silver.<br />

Future research will attempt to use the results of this experiment<br />

to create “smart windows.” These technologies will depend<br />

on the ability to find glass that can conduct electricity while<br />

maintaining transparency. Not only could windows be used as<br />

touch screens, televisions, or thermostats, but they could also be<br />

used to improve household energy efficiency. If windows could<br />

transmit more light and heat, the need for artificial lighting and<br />

heating in houses would decrease, minimizing energy usage<br />

while maximizing comfort.<br />

When asked about his future goals, Chau responded, “I am<br />

hoping to create a multi-disciplinary research facility—consisting<br />

of physicists, chemists, electrical and civil engineers, and psychologists—to<br />

advance smart window technology and examine<br />

the impact of smart windows on buildings and people.”<br />

Chau hopes that someday, we will think of glass as the adaptive<br />

skin of a building, able to change its transparency in response to<br />

weather conditions and user settings. In the near future, you may<br />

be able to control a room’s temperature by changing the settings<br />

on your window.<br />


►Layers of metal created through magnetron sputtering are<br />

shown up close through atomic force microscopy.<br />

www.yalescientific.org<br />

April 2016<br />

Yale Scientific Magazine<br />


GENDER<br />

BENDER<br />

Genetically Modifying Mosquito Sex<br />

BY Sarah Ludwin-Peery<br />

ART BY Emma Healy<br />

CRISPR/Cas9, today’s hottest<br />

genome-engineering<br />

technology, is being used to<br />

change the sex of mosquitos<br />

and potentially prevent the<br />

spread of disease.<br />

For many years, gene editing has been hailed as the future<br />

of medicine. As the genetic basis of disease becomes<br />

clearer, researchers continue to discover more ways to alter<br />

the genome and prevent or cure diseases. Recently, a new<br />

gene editing tool called CRISPR/Cas9—which involves<br />

short, repetitive segments of prokaryotic DNA known as<br />

clustered regularly interspaced short palindromic repeats<br />

(CRISPR) and Cas9, a nuclease that cuts DNA—has become<br />

the primary vehicle for gene manipulation. With any<br />

luck, the CRISPR/Cas9 interference may be used in genetic<br />

research, a variety of therapies, and even the manipulation<br />

of ecosystems.<br />

While these clustered repeats were discovered in 1987,<br />

their function was not understood until the early 2000s,<br />

when researchers discovered that these segments of prokaryotic<br />

DNA are a form of immunity for bacteria. They<br />

store information about previous viral infections, allowing<br />

bacteria to selectively recognize, cut, and degrade foreign<br />

DNA. Since its discovery, CRISPR/Cas9 has become a genetic<br />

editing tool due to its ability to selectively cut DNA.<br />

Researchers have altered the natural CRISPR system to<br />

recognize sequences more specifically and in cell cultures<br />

and eukaryotic organisms, like yeast.<br />


The CRISPR gene-editing model works by inducing breaks in<br />

both strands of DNA. Short pieces of RNA create duplexes, double-stranded<br />

RNA molecules that guide Cas9 to very specific locations<br />

in the DNA. In nature, these RNA duplexes originate from<br />

DNA repeats in the genome, but in the laboratory, these pieces of<br />

foreign RNA can be artificially introduced into a cell, allowing the<br />

nuclease to find a specific site in the host DNA. These RNA guides<br />

can target a DNA sequence up to 20 nucleotides long, providing<br />

great specificity since the mathematical likelihood of that 20-nucleotide<br />

sequence appearing elsewhere in the genome is very small.<br />

After Cas9 cuts the DNA, the double-strand breaks can induce repair<br />

pathways that give gene mutations, insertions, or knockouts. By<br />

using CRISPR to selectively target sequences, these repair pathways<br />

are manipulated to specifically alter the genome. Today, sequence<br />

limitations and issues with off-target effects—editing at untargeted<br />

sequences due to imperfect specificity—keep CRISPR from widespread<br />

use, but many researchers are focused on improving the<br />

system. Hopefully, CRISPR/Cas9 will soon be a viable treatment<br />

option for a range of genetic diseases.<br />

One recently proposed and unique application of CRISPR/Cas9<br />

is to alter the sex of organisms, specifically mosquitoes. In 2015,<br />

a team led by Zhijian Tu and Zach Adelman studied the mosquito<br />

species Aedes aegypti and discovered the genetic basis of sex:<br />

a male-determining factor transcribed from the gene Nix, which<br />

they called the M factor, located on the mosquito’s Y chromosome.<br />

“From the perspective of basic research, we are now in a better position<br />

to decipher the molecular pathway controlling sex determination<br />

in mosquitoes,” Tu said.<br />

The researchers hope to use their newfound understanding of<br />

mosquito sex-determination for genetic manipulation. Altering<br />

gender ratios within mosquito populations may largely benefit<br />

global public health, since only female mosquitos are responsible<br />

for the transmission of blood-borne pathogens. Female mosquitos<br />

must feed on blood to acquire protein and produce eggs, but males<br />

can survive on nectar and fruit juices. This is true for all mosquitoes,<br />

but the Aedes aegypti species was chosen for research because its<br />

genome can be manipulated and it is a common vector for dengue,<br />

chikungunya and Zika viruses. Together these diseases account for<br />

hundreds of deaths per year in Africa, Asia, and the Indian subcontinent.<br />

The dengue virus alone affects 2.4 million people each year,<br />

causing rashes, high fever, and muscle pain.<br />

Current research is limited to the Aedes aegypti species, yet other<br />

mosquitoes also transmit dangerous, vector-borne diseases. For<br />

example, only mosquitoes of the Anopheles genus carry malaria.<br />

However, the researchers stress the versatility of their discovery:<br />

“The approach that successfully identified Nix may also be used to<br />

uncover the M factors in other mosquitoes or insects,” Tu said.<br />

Genetic manipulations that achieve female-to-male conversions<br />

or female-lethality might grant researchers partial control of the<br />

mosquito population. Methods already exist to reduce mosquito<br />

populations, mostly involving insect sterilization, but they are costly<br />

and inefficient. The mass production and release of male mosquitoes<br />

is likely more efficient and cost-effective than sterilization.<br />

According to Tu, it will achieve population reduction and disease<br />

control, but it will also have the benefit of male-bias in subsequent<br />

generations. This male-bias may prevent the spread of deadly diseases<br />

like dengue fever, yellow fever, malaria, and the Zika virus for<br />

generations.<br />

molecular biology<br />


These researchers were not the first to consider a male-determining<br />

factor in mosquitoes, but they were the first to prove its existence.<br />

“The most important result of this research is the discovery<br />

and functional demonstration of a male-determining factor, Nix, in<br />

mosquitoes. Nearly 70 years ago, it was known that such a master<br />

switch gene existed in mosquitoes, but its identity remained elusive<br />

despite strong interest,” Tu said. To discover Nix, the researchers designed<br />

and used an algorithm, a procedure for solving a problem,<br />

that could effectively identify the male-specific DNA sequences. After<br />

it was identified, they demonstrated that Nix was the male-determining<br />

factor by showing that it was necessary and sufficient to<br />

initiate male mosquito development. By manipulating the factor,<br />

they could change a mosquito’s observable sex: overexpression of<br />

the M factor masculinized females, and deletions—obtained using<br />

CRISPR/Cas9—feminized males.<br />

Later, in a 2016 issue of Trends in Parasitology, the same authors<br />

published a paper demonstrating their ability to manipulate the M<br />

factor and other intermediary factors, using CRISPR/Cas9. Two<br />

targeted transcription factors were Dsx and fru, since they undergo<br />

sex-specific splicing events and help determine sex differentiation.<br />

By targeting these factors with the CRISPR/Cas 9 system, the researchers<br />

could convert females to males, allowing for sex separation<br />

and a reduction of the female population. This result builds on<br />

the earlier discovery and manipulation of the M factor to drive sex<br />

change.<br />

While the benefits of gender targeting in mosquitoes appear obvious,<br />

the future of CRISPR/Cas9 remains unclear. Researchers are<br />

unsure if these alterations will effect Aedes aegypti genome stability<br />

in the long term or if gender manipulations will have unforeseen effects<br />

on the ecosystem. CRISPR/Cas9 has already been fraught with<br />

controversy over its ethicality. Certain uses of CRISPR/Cas9 are<br />

highly contested, for example, should CRISPR/Cas9 be used to create<br />

“designer babies,” or is that pushing the boundries of what our<br />

society allows? Someday soon, deciding whether to genetically manipulate<br />

our ecosystems may be an equally controversial conversation.<br />

“CRISPR technology has the potential to significantly improve<br />

our health and environment. But we should also be mindful of the<br />

potential for misuse and proceed with appropriate risk assessment<br />

and regulation,” Tu explains. As science advances, we must consider<br />

what applications of CRISPR/Cas9 are prudent and what pushes the<br />

boundaries too far.<br />

www.yalescientific.org<br />

April 2016<br />

Yale Scientific Magazine<br />





iomedical engineering<br />



A project that began in a Yale classroom has since grown into<br />

a thriving and ambitious startup that promises to revolutionize<br />

the nanotechnology industry and change how we test potentially<br />

contaminated water. Monika Weber, an Electrical Engineering<br />

Ph.D. candidate, founded Fluid-Screen, a startup company now<br />

operating out of Cambridge, MA, that offers a better method of<br />

testing water for pathogens.<br />

Contaminated water is a serious public health concern.<br />

Globally, an estimated 3.4 million people die from contaminated<br />

water each year, and millions more fall ill. Clearly, the ability<br />

to test water for pathogens is essential to reducing the number<br />

of people who succumb to water-borne illnesses. Currently,<br />

the most widely used method of testing water involves sending<br />

a sample to a lab and waiting days for the cell culture results.<br />

Though effective, this method is slow, relatively expensive, and<br />

requires a lab to test the water sample.<br />

Weber’s startup aspires to solve this problem by providing a<br />

faster and cheaper way to test for water contamination. According<br />

to Mark Reed, applied physics and electrical engineering<br />

professor and Weber’s mentor in the project, Fluid-Screen will<br />

provide a portable way to rapidly test water for pathogens. “The<br />

idea of Fluid-Screen is to be able to [test water] in a very nice,<br />

portable format, to be able to test things quickly in the field, and<br />

to potentially do it much cheaper,” said Reed. Fluid-Screen is<br />

producing a hand-held device capable of testing for pathogens<br />

on-site and within 30 minutes, a vast improvement over the<br />

current multi-day process. The Fluid-Screen device will contain<br />

small nanosensors, miniscule devices able to discern different<br />

pathogens, on a disposable microchip. Weber told the Hartford<br />

Courant that each device will use 1 disposable microchip per<br />

test and will cost as little as 1 dollar for each use. This microchip<br />

will be set to detect individual pathogens, such as E. coli, by<br />

pulling them out of the water sample with an electronic field. The<br />

device will then relay test results to a smartphone. By allowing<br />

for faster and more cost-efficient water testing that can bypass<br />

laboratories, this technology could reach underdeveloped<br />

countries where lab testing is not yet available or not financially<br />

viable.<br />

Reed explains that Fluid-Screen employs a phenomenon called<br />

dielectrophoresis, where a non-uniform electric field imparts a<br />

force on a neutral particle or object, such as a cell. “You create<br />

an electronic track able to pull out [the pathogens] that you are<br />

looking for when you pass water over it,” he said. The device will<br />

be able to be set to detect a multitude of pathogens, so that only<br />

a single device will be required to test water for a wide range<br />

of bacteria. The device will also be incredibly sensitive, cable<br />

of discerning as little as a single bacterium in a 100 mL sample<br />

with 99 percent accuracy.<br />

Although dielectrophoresis is not a newly discovered<br />

phenomenon, Weber and Reed were the first researchers to<br />

apply it to this type of pathogen detection. “Every once in a<br />

while, you stumble into something where people have not<br />

www.yalescientific.org<br />

delved into it enough, and that’s what I saw here—other people<br />

missed a few points,” said Reed. He credits the discovery of this<br />

novel application to his multidisciplinary lab, which contains<br />

researchers focusing in electrical engineering, applied physics,<br />

biomedical engineering, mechanical engineering, and chemistry.<br />

“That is just the kind of environment that I like, because I think<br />

that it opens up a lot of interesting potential new applications,”<br />

said Reed, who has had other former students succeed in<br />

founding startup companies. SeLux Diagnostics, also based in<br />

Cambridge, MA, was founded in 2014 by two former members<br />

of Reed’s lab and is developing an assay to simplify laboratory<br />

diagnostics. While the company’s technology was not developed<br />

in Reed’s lab, he says that he is still in contact with his former<br />

students and may collaborate with them in the near future.<br />

According to Reed, Weber’s project began about four years<br />

ago, when she was taking a class in microelectromechanical<br />

systems (MEMS). “The class project was to come up with some<br />

sort of interesting device idea,” he said. Weber came up with the<br />

idea for Fluid-Screen, and then Reed’s lab received a grant from<br />

the Defense Threat Reduction Agency, a government agency<br />

that is part of the US Department of Defense, to test the viability<br />

of the idea and further develop the underlying science. Weber<br />

continued to develop the idea, eventually winning additional<br />

funds from several student startup competitions, including<br />

the prestigious MassChallenge competition. Overall, she has<br />

secured more than $340,000 in total for Fluid-Screen and has<br />

received a patent for the concept. Since Yale is a non-profit<br />

organization, it does not allow companies to use its lab space:<br />

once Weber launched her company, she stopped using Reed’s lab<br />

to develop the Fluid-Screen technology and moved her company<br />

to Cambridge, MA.<br />

Weber looks to capitalize on Fluid-Screen’s early success<br />

by taking her project to the market. Fluid-Screen has already<br />

prototyped a product and plans to have it commercially<br />

produced by this September. Once Weber succeeds in<br />

manufacturing a device to test water, she plans to expand the use<br />

of her technology to cover other important applications. “Once<br />

we perfect the device with water testing, we intend to move on<br />

to other applications, such as blood and urine testing,” Weber<br />

said in her interview with the Hartford Courant. With these new<br />

abilities, the device could also replace the need for a lab to test<br />

blood and urine for bacteria.<br />

Clearly, Fluid-Screen seems poised to positively benefit the<br />

world by producing a product that will be faster, cheaper, and<br />

more effective than lab testing. “I think the mission of a company<br />

is important. I'm proud to do work that’s making a difference,”<br />

Weber told the Hartford Courant. And if her company continues<br />

to expand, she could stand to receive a large payday. Fluid-Screen<br />

estimates a 1 billion dollar potential market for its water testing<br />

product alone. Money aside, Fluid-Screen could significantly<br />

impact and improve water testing, especially in parts of the<br />

world that struggle with polluted and contaminated water.<br />

April 2016<br />

Yale Scientific Magazine<br />



GUIDED<br />

BIONIC<br />

LIMBS<br />



In the<br />

United States,<br />

approximately<br />

12,000 people<br />

become paralyzed<br />

each year due to<br />

spinal cord<br />


medicine<br />


What if we had the technologies to help paraplegics and quadriplegics<br />

walk again—for instance, bionic limbs and exoskeletons<br />

controlled solely by thoughts? While these technologies sound like<br />

they belong in science fiction novels, they may become a reality in<br />

the near future.<br />

Just this February, a research team led by Dr. Thomas Oxley at<br />

the University of Melbourne published a paper in Nature Biotechnology,<br />

detailing their development of a new device to measure<br />

patients’ brain signals. This device, called the “stentrode,” is a tiny<br />

cigar-shaped net that measures only a few millimeters wide. It is<br />

light and flexible, and it can be collapsed and inserted into a vein<br />

near the motor cortex, the region of the brain controlling voluntary<br />

movement.<br />

Once settled into the brain, the stentrode expands to its original<br />

shape, and the electrodes embedded in the net begin to record the<br />

surrounding electric signals from nerve cells. Each electrode can<br />

pick up the signals fired by about 10,000 neurons. Delicate wires<br />

deliver these signals from the brain to the chest, which contains a<br />

wireless transmission system. This transmission system can convert<br />

the electric signals of the brain into special signals which are<br />

recognized by bionic limbs or an exoskeleton.<br />

According to the researchers, the stentrode offers us a novel<br />

method of looking into the inner workings of the brain. Not only<br />

is it biocompatible and minimally invasive, the stentrode delivers<br />

high-resolution signals of brain activity.<br />

The development of the stentrode was a huge project involving<br />

a team of researchers from the University of Melbourne, the Royal<br />

Melbourne Hospital, and the Florey Institute of Neuroscience<br />

and Mental Health. Dr. Oxley, who spearheaded the project, is a<br />

neurologist at the University of Melbourne and an endovascular<br />

neurology fellow at Mount Sinai Hospital in New York. To assemble<br />

the team, he reached out to top researchers in Australia, many<br />

of whom had already been involved with a project to develop a<br />

bionic eye.<br />

The researchers tested the stentrode in sheep brains for a period<br />

of six months, comparing the functionality of the device with that<br />

of a more traditional brain implant. They initially faced challenges<br />

while developing the device; to engineer the intricate structure<br />

of the stentrode, they went through several hundred iterations of<br />

unsuccessful precursors. The final design used a flexible material<br />

called nitriol, which is also found in bra underwires and glasses<br />

frames.<br />

Once they had achieved a final model, the researchers inserted<br />

the stentrode into the brains of healthy living sheep. Within hours<br />

of the operation, which was painless and quick, the sheep were<br />

walking and behaving normally. The researchers started picking up<br />

electric signals within nine days. They were able to detect signals<br />

with frequencies of 190 Hz—an exciting finding because signals<br />

between 70 Hz and 200 Hz are associated with the motor cortex.<br />

Previous devices used to record brain signals were highly invasive<br />

and difficult to insert. In order to insert these devices, surgeons<br />

would remove a portion of the skull and attach the electrodes to the<br />

surface of the brain or fire them into the tissue with a gun powered<br />

by air pressure. Since this invasive insertion process requires openbrain<br />

surgery, it often results in complications, such as infection,<br />

brain trauma, and chronic inflammation. Furthermore, the body<br />

can set off an immune response and cover the electrodes in scar<br />

tissue, preventing them from functioning.<br />

www.yalescientific.org<br />


►The stentrode is a revolutionary device for recording brain signals,<br />

measuring only a few millimeters wide.<br />

On the other hand, the stentrode can be inserted painlessly and<br />

non-invasively without complex surgery. To insert the stentrode, a<br />

catheter holding the device is positioned over a blood vessel near<br />

the motor cortex. The catheter is removed after the stentrode is<br />

deployed. Then, the stentrode travels to the motor cortex and expands<br />

to fit into the blood vessel, where it can begin picking up<br />

electric signals from the brain.<br />

The researchers explain that the stentrode holds many potential<br />

advantages compared to previous devices, including “improved<br />

biocompatibility, high-resolution signal transduction, and longterm<br />

functionality.” The stentrode, once inserted into the brain,<br />

can remain in place and transmit signals for long periods of time<br />

without damaging brain tissue. In addition, the stentrode accesses<br />

information-rich signals from deep within the brain that previous<br />

devices could not pick up.<br />

The stentrode has many exciting possible applications, such as its<br />

potential usage in bionic limbs to restore movement to paralyzed<br />

patients. The electric signals of the motor cortex could be detected<br />

by the stentrode and sent to control bionic limbs or exoskeletons—<br />

for the first time, these mechanical devices would be powered simply<br />

by thought.<br />

The researchers predict that learning to use such devices would<br />

take many months of adjustment. Patients would have to master<br />

using their thoughts to direct an electronic limb or exoskeleton.<br />

Oxley likens this process to learning how to play the piano—first<br />

figuring out how to coordinate your hands to strike the keys in the<br />

right sequences, and then practicing to the point where playing the<br />

piano becomes second nature.<br />

Other potential applications of the stentrode include monitoring<br />

the brain activity of patients with neurological and mental disorders,<br />

such as Parkinson’s Disease, motor neuron disease, OCD, and<br />

depression, or even predicting and managing seizures in epileptic<br />

patients. The researchers plan to conduct a clinical trial of the stentrode<br />

with human subjects in 2017. Dr. Oxley is optimistic that<br />

within six years, the stentrode will become commercially available<br />

for patients with paralysis and other conditions. And if his prediction<br />

is correct, we will soon undergo a revolution in the way we<br />

look at the human brain.<br />

April 2016<br />

Yale Scientific Magazine<br />


I<br />


SC ENCE<br />


In the early 1950s, manufacturers began to use the compound<br />

bisphenol A—more colloquially known as BPA—as a strengthening<br />

agent in commercial plastics. It wasn’t until 40 years later that researchers<br />

began to suspect that synthetic chemicals like BPA could disrupt the<br />

endocrine system, a collection of glands that secrete hormone signals.<br />

Further research eventually shed light on BPA’s harmful reproductive,<br />

developmental, and carcinogenic effects. Retailers began to remove BPA<br />

from consumer products, and policy changes restricting BPA use ensued.<br />

Now, even plastics not containing BPA are coming under fire: a<br />

recent UCLA study published in Endocrinology suggests that BPA-free<br />

alternatives are not safer than products containing BPA. The findings may<br />

revamp how consumers use plastic food containers or even spur greater<br />

commercial and policy changes.<br />

Since the removal of BPA from commercial products, bisphenol S (BPS)<br />

has acted as a substitute. It was thought to be more heat-stable and less<br />

disruptive to the endocrine system, but research done in Nancy Wayne’s lab<br />

at UCLA shows a striking similarity between the effects of BPS and those<br />

of BPA. Her lab compared the effects of both chemicals on the zebrafish<br />

reproductive neuroendocrine system, which regulates cell development in<br />

the regions of the brain controlling reproduction. Zebrafish are a popular<br />

model for studying embryonic development because their embryos<br />

are transparent, facilitating microscopic visualization. The researchers<br />

monitored the developmental changes in embryonic neurons in response<br />

to BPA or BPS, finding that both produced similarly detrimental effects.<br />

The researchers also looked at how BPS and BPA affected key endocrine<br />

pathways. For example, the study found a receptor to estrogen (a female<br />

sex hormone) whose gene expression was increased in the presence of<br />

BPA and BPS. Overstimulation of this receptor, and other disruptions of<br />

the estrogen pathway, are linked to disorders like precocious puberty—<br />

puberty at a premature age—in human females. The study also found that<br />

BPA and BPS disrupt pathways involving thyroid hormone receptors,<br />

which regulate metabolism, and aromatase, an enzyme that helps produce<br />

estrogen.<br />

Wayne herself is wary of these synthetic chemicals. “The day our<br />

postdoc showed me the data, I went home and got rid of all the plastic<br />

food containers in my house. I probably dumped hundreds of dollars’<br />

worth of food, and I bought glass and ceramic containers instead,” Wayne<br />

said. She notes that not everyone has the disposable income to make that<br />

more expensive choice—instead, she encourages consumers to demand<br />

that manufacturers produce more stable plastic products that release less<br />

endocrine disruptors.<br />

“This is an important message to get out: BPA-free is a marketing<br />

scheme, or scam. Industries are swapping one endocrine-disrupting<br />

chemical for another, and they’re calling it BPA-free because BPA has<br />

gotten a lot of media attention,” Wayne said.<br />

The major obstacle to Wayne’s research was not scientific, but financial.<br />

She contacted the National Institute of Environmental Health Sciences<br />

multiple times, but they had little interest in BPA or BPS research.<br />

UCLA continued to support Wayne’s research, and her publication in<br />

Endocrinology was financed with money from the Chinese government,<br />

since the lead researcher of the study was Wenhui Qiu, a visiting graduate<br />

student from Shanghai University.<br />

Yale researcher John Elsworth, who also studies the effects of endocrine<br />

disruptors, believes that Wayne’s research adds to a growing body of<br />

literature on BPS. According to him, one merit of the study was that<br />

it tested a wide range of BPS exposure levels. “Responses to low doses<br />

cannot be reliably predicted from changes observed at higher doses,”<br />

Elsworth said. He also praised the study for pinpointing the biochemical<br />

pathways affected by BPS by using drugs to reverse the observed changes<br />

in these genes and proteins. However, he feels that more research needs<br />

to be done: “Because of species differences in biochemistry, physiology,<br />

endocrinology and regulation of developmental processes, controlled<br />

studies in nonhuman primates would provide the most accurate<br />

indication of the impact of BPA and BPS on humans,” Elsworth said.<br />

Wayne agrees about the need to go further, saying she would like to<br />

see future research, possibly within her own lab, exploring the impact<br />

of lifelong exposure to low-level endocrine-disrupting chemicals. Her<br />

current research focuses on the reproductive system, but endocrine<br />

disrupters may also be involved in cancer, obesity, and other diseases.<br />

Moreover, BPA and BPS are just the beginning; we are exposed to many<br />

different types of endocrine-disrupting chemicals on a daily basis.<br />

“We already know that we’re poisoning ourselves. But what is it that we<br />

can eliminate to help decrease the risk?” Wayne asked.<br />


►A water bottle bearing the a “BPA-free” logo, marketed towards<br />

consumers as a better alternative to plastic products containing BPA.<br />

34 Yale Scientific Magazine March 2016 www.yalescientific.org

BLAST<br />

from<br />

the<br />

PAST<br />

Antibiotics Past and Present<br />


With antibiotic resistance on the rise, researchers are frantically<br />

searching for ways to counter new bacterial “superbugs.” Instead<br />

of looking for new state-of-the-art solutions, researchers might<br />

have more success dusting off ancient medieval texts. Just last<br />

summer, scientists discovered that a one-thousand-year-old garlic<br />

and onion remedy for eye infections may hold the key to treating<br />

certain antibiotic-resistant infections.<br />

A team led by Freya Harrison and Steven Diggle at the University<br />

of Nottingham tested the remedy, found in a 10th century<br />

Anglo-Saxon manuscript, against methicillin-resistant Staphylococcus<br />

aureus (MRSA). While the individual ingredients were<br />

known to hold limited antibacterial potency, when combined,<br />

they were able to consistently kill up to ninety percent of MRSA<br />

bacteria. “The fact that the whole recipe—all the ingredients and<br />

the specific preparation instructions—is required to make the<br />

mixture work is fascinating,” Harrison said. “It suggests that there<br />

might have been some empirical method present in at least some<br />

of the medical treatments that early medieval people developed.”<br />

Prior to this study, experts considered the efficacy of other medical<br />

interventions from antiquity, but few quantitative studies had<br />

empirically proved their abilities. Harrison and Diggle’s work has<br />

demonstrated that further exploration of seemingly outdated<br />

therapies may help to improve current medical treatments. According<br />

to Diggle, they are still looking into other historical texts<br />

for effective medicines. “Our ancestors have done experiments for<br />

us and so these books are an extremely useful starting point,” Diggle<br />

said.<br />

Medieval potions are not the only promising historical treatment:<br />

A look into the more recent past has led scientists to consider<br />

bacteriophage therapy as a tool for fighting infections. Bacteriophages<br />

are viruses that infect and kill bacterial cells. However,<br />

bacteriophages are unable to infect human cells and so were used<br />

to treat a variety of infections in the 1920s and 1930s. Although<br />

physicians of the time did not fully understand how bacteriophages<br />

functioned—and therefore did not always design the most effective<br />

treatments—bacteriophage therapy was an important tool<br />

to fight infections prior to the emergence of antibiotics.<br />

Since the advent of antibiotics, their use has skyrocketed. Today,<br />

antibiotics are often used in excess to treat patient infections or<br />

to increase agricultural productivity. Consequently they drive the<br />

evolution of antibiotic-resistant strains of microbes, like MRSA.<br />

Antibiotic resistance affects millions of people who cannot obtain<br />

drugs to effectively treat their infections. It is a serious threat<br />

to medicine, and researchers are now exploring alternative treatments,<br />

like bacteriophage therapy, for infectious diseases.<br />

Bacteriophage technology is currently used to target foodborne<br />

illness, which affects approximately 9.4 million people in the United<br />

States each year. One biotechnology company, Intralytic Inc.,<br />

has been designing medical interventions against pathogenic bacteria<br />

since 1998. The company recently created two products—<br />

ListShieldTM and EcoShieldTM—that combine bacteriophages<br />

targeting the same bacterium. Both of these products are designed<br />

to kill bacteria during food processing. ListShield is now an FDA<br />

approved food additive, and it targets Listeria monocytogenes, an<br />

infection-causing bacterium found on dairy products, meats, and<br />

raw produce. This bacteriophage “cocktail” kills pathogens after it<br />

is sprayed directly onto food or other areas of a food processing<br />

plant that may harbor the bacteria, like drains or floors. EcoShield<br />

is similar to ListShield, but it targets Escherichia coli, a bacterium<br />

responsible for 62,000 cases of foodborne illnesses every year.<br />

Both products are harmless to everything except the bacteria they<br />

were engineered to target.<br />

Another newly emerging bacteriophage technology relies on<br />

the isolation of enzymes called lysins. When bacteriophage target<br />

a bacterial cell, they produce lysins that cause bacterial cells to<br />

rupture. Scientists recently discovered that lysins effectively fight<br />

certain bacteria independently, without other components of the<br />

bacteriophage. Bruce Seal, a researcher for the US Department of<br />

Agriculture, has successfully used lysins to kill strains of Clostridium<br />

perfringens, a bacterium that causes food poisoning in humans<br />

and necrotic enteritis in poultry—a disease that devastates<br />

the poultry.<br />

From medieval eye remedies to bacteriophage technology, history<br />

may offer us the tools needed to help fight modern disease.<br />

Despite recent innovations, a blast from the past may be needed to<br />

solve some of today’s most challenging puzzles in medicine.<br />

www.yalescientific.org<br />

April 2016<br />

Yale Scientific Magazine<br />


KRISTO MENT (MC ‘17)<br />




Yale junior Kristo Ment is making waves, literally. As we sat down<br />

for an interview, he drew the arc of a light wave with his right arm,<br />

coming at us from a hypothetical supernova—a celestial explosion.<br />

He stretched the wave out, demonstrating a redshift: the shift of light<br />

from space towards longer wavelengths, a consequence of the ever-expanding<br />

universe.<br />

Ment’s own universe has expanded several times. He came to Yale<br />

from a small town in Estonia called Pärnu. Home to just under 40,000<br />

residents, ninety-five percent of whom are Estonian or Russian, Pärnu<br />

lacked the cultural and academic diversity. Nevertheless, his circumstances<br />

did not hamper his learning—at the age of three, Ment<br />

began to read about science and nature. Later on, he competed in international<br />

math and science competitions. Still he felt he wanted to<br />

live in a city where he could do “real science.”<br />

After high school graduation, Ment moved to New Haven and decided<br />

to pursue a degree in astrophysics Yale. He described the transition<br />

as gratifying. Moving to New Haven allowed him to explore<br />


►At a January conference in Paris, Kristo Ment ’17 presented a<br />

microlensing database to a community of scientists involved in the<br />

pursuit of detecting planets.<br />

a new region of the world. “This idea of starting over from zero is<br />

something that I found incredibly exciting,” Ment said.<br />

Since making the move, Ment has continued to develop his passion<br />

for astrophysics and has been met largely with success. After taking<br />

intensive introductory physics, Ment sought the mentorship of his<br />

professor Charles Baltay. The summer after his freshman year, Ment<br />

worked with Baltay, studying pulsating stars called RR Lyrae variables.<br />

These stars are of particular interest to astrophysicists as their<br />

properties can be used to determine the distance between galaxies.<br />

Ment now works with Baltay studying redshifted light from supernovae.<br />

He examines data from explosions occurring close to Earth in<br />

astronomical space and time. These nearby supernovae, when compared<br />

to high-redshift supernovae that are further away, help to illustrate<br />

how the universe is expanding and how light is stretched.<br />

Contrary to popular belief, Ment does not spend much of his time<br />

looking through a telescope. Instead, much of his work consists of<br />

sitting in front of a computer, writing code, running programs, and<br />

analyzing data.<br />

Still, one new, high-capacity telescope excites him: NASA’s Wide-<br />

Field Infrared Survey Telescope (WFIRST). From space, the telescope<br />

will survey millions of galaxies and has the potential to detect thousands<br />

of supernovae. “WFIRST will be the best telescope we have ever<br />

sent to space,” Ment said.<br />

Ment is excited by WFIRST’s potential to detect supernovae and<br />

planets using microlensing. Microlensing relies on gravity’s effect<br />

on light; if light from a distant source is bent or distorted by a star’s<br />

gravity—especially if the star has a planet orbiting around it—then<br />

the telescope will display a huge brightening of light. Since scientists<br />

use different telescopes and models all around the world, Ment saw<br />

a need to consolidate the information about microlensing from various<br />

sources. The summer after his sophomore year, Ment worked at<br />

Heidelberg University in Germany to compile an online database. In<br />

January, he presented his work to 100 members of the International<br />

Conference on Microlensing. Since he finished compiling the database,<br />

research groups around the world have found dozens of new<br />

planets.<br />

Currently enrolled in three graduate-level astrophysics classes in<br />

addition to studying French and Roman history, Ment sometimes<br />

questions his own sanity. “I wake up almost every morning feeling<br />

like a masochist,” Ment said.<br />

Nevertheless Ment considers himself lucky to be at Yale. Its diverse<br />

community and resources have allowed him to expand his ambitions,<br />

passions, and expertise.<br />

36 Yale Scientific Magazine April 2016 www.yalescientific.org


BRIAN KOBILKA (<strong>YSM</strong> ‘81)<br />



Brian Kobilka has certainly had a successful career in research: he<br />

runs a biochemistry lab at Stanford, has published widely in top journals<br />

such as Science and Nature, and won a Nobel Prize in Chemistry<br />

in 2012 for his research on the adrenaline receptor. He even fondly recalls<br />

a colleague calling him an “irrational optimist” for his constant<br />

persistence in the lab. Kobilka’s personality and accomplishments suggest<br />

he is the perfect researcher, but he did not immediately realize research<br />

was his calling.<br />

As a child, Kobilka wanted to become a practicing clinician. He grew<br />

up in the small town of Little Falls, MN, where he admired his childhood<br />

pediatrician. Since clinical medicine was a well-paying and stable<br />

job, it seemed like a great career option. With parental encouragement,<br />

Kobilka studied biology and chemistry at the University of Minnesota<br />

Duluth, intent on preparing for medical school. Although he worked<br />

on several small research projects, he did not know if he would succeed<br />

as a researcher and set out to pursue an MD at the Yale School of<br />

Medicine.<br />

Kobilka describes moving to Yale as shocking—living in an urban<br />

environment and interacting with intimidating classmates were entirely<br />

new experiences. “Yale was a really special place, though I don’t know if<br />

I knew it before I went there,” Kobilka said. “Our basic science lecturers<br />

encouraged us to really understand things in molecular and mechanistic<br />

detail, and certainly didn’t teach us to pass board exams. It was really<br />

a great place to go to medical school. And I think it had quite an impact<br />

on what I ended up doing.”<br />

The challenges Kobilka faced at Yale played a huge role in his eventual<br />

decision to become a researcher. In particular, he enjoyed the original<br />

scientific research he was required to conduct. One summer, Kobilka<br />

did field research on dengue fever in Malaysia, preparing for a potential<br />

thesis project. The project was not entirely successful, but it sparked his<br />

interest in basic research, leading him to his eventual thesis project: a<br />

study of the genetic diversity of the rotavirus, which causes inflammation<br />

and irritation in the gastrointestinal tract.<br />

After his residency, Kobilka completed a four-year research fellowship<br />

at Duke. He worked in Robert Lefkowitz’s lab, studying G protein<br />

coupled receptors (GPCRs), an important class of molecules that carry<br />

signals into the cell. In the Lefkowitz lab, Kobilka and his colleagues<br />

isolated and generated a gene encoding an adrenaline receptor—the<br />

receptor that initiates the “fight or flight” response in cells—which he<br />

would later characterize at Stanford.<br />

Kobilka went years without success, and his time in the Lefkowitz lab<br />

was a turning point in his career. When asked how he continued in the<br />

face of failure, Kobilka joked that he always found solace in the logical<br />


►Kobilka’s lab on the day the Nobel was announced.<br />

nature of science and in the fact that there was always an explanation for<br />

a failed experiment. He also contributes his success to exchanges with<br />

gifted postdocs that exposed him to a variety of fields—from biochemistry<br />

to pharmacology—and ultimately prepared him to start his own<br />

lab at Stanford.<br />

At Stanford, Kobilka continued to study the adrenaline receptor and<br />

eventually attained molecular “snapshots” documenting the act of signaling.<br />

Using these clues, he could explain exactly how adrenaline signaling<br />

works, atom by atom, and as a result, he won the 2012 Nobel<br />

Prize in Chemistry with his mentor, Lefkowitz. Now, Kobilka characterizes<br />

the structures, functions, and dynamics of other important receptors<br />

in the GPCR family. He just published a study on opioid receptors,<br />

the molecules that pass pain-relieving signals into the cell.<br />

Reflecting on his own path, Kobilka explained why he eventually<br />

chose research: “If you land in an area of research that’s interesting and<br />

that fundable, it’s a great way to spend your life. You’ll always be challenged<br />

and will constantly be exposed to young people often smarter<br />

and more creative than you are. The only thing it lacks is financial security,<br />

both for the lab and for yourself and your family.”<br />

Throughout Kobilka’s career, long-term failure was always a possibility,<br />

but he continued until he was met with success. Though winning<br />

the Nobel Prize was an enormous accomplishment, his decision to shift<br />

paths from practicing medicine to research was perhaps an even greater<br />

one because he found the courage to pursue his interests. Kobilka’s story<br />

is not only a lesson in perseverance, but also in following your heart.<br />

www.yalescientific.org<br />

April 2016<br />

Yale Scientific Magazine<br />



review<br />




At first glance, The Only Woman in the Room is just another portrayal<br />

of a common narrative, documenting a woman who liked science<br />

but was frightened away from that male-dominated field. Yet author<br />

Eileen Pollack’s work ought not to be so easily dismissed. Indeed, her<br />

work is a standout in a cluttered field. Her account is compelling—<br />

and by extension terrifying—because of how personal it is. Pollack’s<br />

experiences show that certain stereotypical male behaviors are often<br />

too real and too discouraging. While she enjoyed studying physics at<br />

Yale, and was an exceptional student, she did not find the same sort of<br />

community or support that she discovered in her English classes.<br />

Pollack takes on the traditional narrative with the skill of a talented<br />

writer and the critical design of a scientist. Tracking her trajectory from<br />

discouraged middle-school-romantic to frantic Yale undergraduate, she<br />

considers the bureaucratic and behavioral paradigms that contribute to<br />

gender inequality in STEM. Instead of dwelling on the statistics, she<br />

uses them as a foundation for her own personal narrative.<br />

As a writer and teacher, Pollack knows the impact a good story can<br />

have: “The studies were already out there and most people weren’t<br />

listening,” she explains, referring to the gender gap in STEM. She<br />

understands that most roadblocks for female scientists are social,<br />

psychological, and sometimes even romantic, and they can arise just<br />

as often from peers as professors. Pollack encourages other women to<br />


be equally introspective. “By getting so personal about my own story, I<br />

wanted to inspire other women to do the same—to get a conversation<br />

going,” Pollack said. Her goal is to reach aspiring undergraduates,<br />

but also the girls who were never encouraged to move past LEGOs.<br />

“The women who aren’t in the room at all,” Pollack said. She also<br />

hopes to educate male scientists who may be unaware of the immense<br />

repercussions of their casual offhand comments. Her book does<br />

not speak for every female scientist and does not attempt to, but it<br />

successfully creates broader conversations among its readers.<br />


►As much as we’d like to think otherwise, social barriers still block<br />

many women from success in STEM.<br />


Just a few seconds into Raising the Dinosaur Giant, David<br />

Attenborough’s voice fills the room and begins to set the scene for a<br />

spellbinding documentary. Attenborough, known for narrating The Blue<br />

Planet, speaks with a passion that is infectious and inspiring. In Raising<br />

the Dinosaur Giant, his astute observations and probing questions<br />

gently guide the viewer through the discovery of the largest land animal<br />

to ever walk the Earth—perhaps too gently at times. Although easily<br />

understood and visually resplendent, the PBS documentary can seem<br />

superficial at times.<br />

The discovery began in Argentina, when a local farmer found an eightfoot-long<br />

femur, the largest ever discovered. Subsequent digs unearthed<br />

the complete skeleton of this massive creature, dubbed “titanosaurus.”<br />

In an effort to effectively communicate the gargantuan stature of this<br />

prehistoric beast, Attenborough makes helpful comparisons to everyday<br />

objects. The titanosaurus would have measured 121 feet, approximately<br />

three times the length of a school bus. Its huge heart, six feet in<br />

circumference, would have pumped 90 liters of blood with each beat<br />

and weighed more than three grown men.<br />

The documentary’s visuals are equally astonishing. Real-life footage<br />

from paleontological digs is combined with computer-generated images<br />

of a titanosaur, painting a detailed picture of what the animal must have<br />

looked like. These computer generated images also aided paleontologists<br />

in their discussions about the bones, helping them determine how<br />

the skeleton fit together. Their efforts culminated in the creation of a<br />


►Raising the Dinosaur Giant describes how paleontologists piece<br />

together information to recreate the fascinating story of dinosaurs.<br />

physical model of the titanosaurus. One particularly mesmerizing shot<br />

in the documentary involves Attenborough walking through the vast<br />

warehouse that contained this model, gazing upwards in awe.<br />

While the documentary was engaging, it could have been improved by<br />

extended interviews with paleontology experts. Members of the research<br />

team gave short statements, but overall, the program lacked sufficient<br />

scientific explanations, especially regarding how the computer model<br />

was generated. In addition, if filmmakers had fleshed out the historical<br />

perspective of paleontology and the previous dinosaur discoveries,<br />

they could have intensified the perceived impact of this finding. Minor<br />

quibbles aside, Raising the Dinosaur Giant was a captivating episode<br />

that served as an exciting reminder that, even as society races into the<br />

future, much of the past remains unearthed.<br />

38 Yale Scientific Magazine April 2016 www.yalescientific.org

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