Princeton Research Day highlights student and early-career work

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MORE THAN 150 undergraduates, graduate students and postdoctoral researchers presented their work at the first Princeton Research Day held May 5, 2016.

The event highlighted research from the natural sciences, engineering, social sciences, humanities and the arts in formats including talks, poster presentations, performances, art exhibitions and digital presentations — all designed with the general public in mind.

“It’s a wonderful cross section of the research enterprise at Princeton,” said Dean for Research Pablo Debenedetti, the Class of 1950 Professor in Engineering and Applied Science, and professor of chemical and biological engineering.

In all, Princeton Research Day presented an important opportunity for undergraduates, said Dean of the College Jill Dolan, the Annan Professor in English and professor of theater in the Lewis Center for the Arts.

“Princeton is one of the very few universities in the world where undergraduate students are encouraged to do the kind of original research that every single undergraduate on this campus does,” Dolan said. “So taking the opportunity at the end of the year to do a major public event in which students can present that work is groundbreaking.”

Princeton Research Day was a collaborative initiative between the offices of the dean of the college, dean of the faculty, dean of the graduate school and the dean for research. The second Princeton Research Day is scheduled for May 11, 2017. –By Michael Hotchkiss

Big answers from small creatures

A graduate student tracks the spread of viruses from bats to humans in Madagascar

By Cara Brook

IT IS SPRINGTIME in the Makira-Masoala peninsula of northeastern Madagascar, and the lychee trees are in full fruit. I sit crouched with my research team in camping chairs as dusk settles, our eyes intent on Rousettus madagascariensis, one of three species of endemic Malagasy fruit bat. The fox-faced bats flit deftly amongst the leafy branches, dodging our nets as they search out juicy pink fruits for their evening meal.

Our quiet vigil is interrupted by the arrival of a whistling gray-haired man from the nearby village who carries a net strung on a pole in one hand and a garish yellow plastic fuel can in the other. With a nod to us, he strides up to a neighboring tree and expertly scoops five of the feasting bats, pins the net to the ground with a bare hand, and coaxes the bats one-by-one into his yellow can. Mission accomplished, he straightens up with a wink and turns back home, rattling his can of bats in time to his whistle as he walks.

Handeha hihinina andrehy izy?” I ask my Malagasy colleagues in astonishment. Is he going to eat the bats? Laughing at my horror, they nod in affirmation.

Bats as reservoirs

I study zoonotic diseases, infections that transmit from wildlife to humans, as a graduate student in Princeton’s Department of Ecology and Evolutionary Biology. Bats are native reservoir hosts — meaning they host viruses without getting sick — for a number of the world’s most dangerous human diseases, including rabies, Ebola and SARS. I want to understand how bats host these viruses without getting sick and what factors contribute to the viruses’ spillover to human populations.

Field lab

Graduate student Cara Brook (rear) and colleague Christian Ranaivoson, a graduate student at the University of Antananarivo and an intern with the Pasteur Institute of Madagascar, process fresh bat fluids in their field lab in Maromizaha, Madagascar, in September 2014. (Photo by Deborah Bower.)

A lot of my work involves building mathematical models to understand disease. When I started graduate school, I barely understood what a “model” was. Four years later, I recognize that a model is simply a representation of reality — it can be physical, like a model of the solar system; experimental, like a mouse that a scientist infects to monitor disease progression; or mathematical, like the equations we use to describe disease transmission in my field of disease ecology.

The goal is to build simple models that still adequately represent reality. One of my professors, Bryan Grenfell, once told me, “If you apply a complex model to a complex system, then you have two things that you don’t understand.” If we can understand our models, then we can learn by observing the differences between these models and the more complex reality.

In disease ecology, our simple models are mathematical equations that class all potential disease hosts — bats, in my research — into three categories: (1) susceptible to infection; (2) currently infected; or (3) recovered from infection and now immune. We use our equations to predict how the proportion of hosts within each category changes over time, and then we collect data to determine whether our predictions match reality.

Remote corners

One of the ideas we are testing is whether bats are fundamentally different from other mammals in their capacity for resisting or tolerating viral infections. I build models depicting the spread of infected cells within individual bats and explore the physiological processes that might allow a bat cell to host a replicating virus without experiencing the cellular damage that causes the host to feel sick.

In the lab, I grow layers of bat cells, infect them with virus, and monitor cell-to-cell viral spread. Then I compare these data with what is predicted in my models. If the data match the model, then maybe the mechanism for disease mitigation that I chose for my model also is the one used in real life.

At a population level, bat-virus transmission, including spillover, peaks in the winter, and we want to know why. I build population-level transmission models that incorporate different seasonal pathways to cause winter infections, then I try to match those models to data. Collecting field data is hard — I spend years trekking to remote corners of Madagascar, mastering obscure Malagasy dialects, and rigging complex pulley systems out of nets, fishing lines and carabiners.

At the end of it all, like the man in Makira- Masoala, I catch a few bats. Instead of cooking them for dinner, however, I use fine-gauge needles, cryogenic vials and sterile swabs to collect their blood and other bodily fluids before I let them go. I haul the fluids in vats of liquid nitrogen to the laboratories of the Pasteur Institute of Madagascar in the capital city of Antananarivo. From there, samples are shipped to collaborators in London, Berlin, New York and Washington, D.C., while others remain in-country. My collaborators and I perform a variety of tests on these transported fluids to ascertain whether the bats were susceptible, infected or recovered from infection at the time of sampling.

When all is said and done, the results are sometimes difficult to interpret. Science is a gradual process, and the goal is to always narrow the window of possible hypotheses at least a little bit.

For me, science is a recognition of, as John Steinbeck put it, “how man is related to the whole thing.” I’m still trying to understand how humans fit into the zoonotic cycle of disease. I’m nearing the end of my Ph.D., but I have enough questions to keep me going for a lifetime.

Cara Brook is a fifth-year doctoral student. Her advisers are Andrew Dobson, professor of ecology and evolutionary biology; Bryan Grenfell, the Kathryn Briger and Sarah Fenton Professor of Ecology and Evolutionary Biology and Public Affairs; Andrea Graham, associate professor of ecology and evolutionary biology; and C. Jessica Metcalf, assistant professor of ecology and evolutionary biology and public affairs. Brook’s research is funded by the National Science Foundation, the National Geographic Society and PIVOT, a Madagascar-based health care nongovernmental society.

The literature of madness and how it shaped modern psychiatry

IN 1890, THE RUSSIAN PHYSICIAN and writer Anton Chekhov traveled across Siberia to document the lives of prisoners sentenced to a remote penal colony on Sakhalin Island. The visit inspired not only a nonfiction exposé but also several works of fiction, including a famous short story, “Ward Number Six,” about the ill-fated friendship of a doctor and a paranoiac patient in a rural Russian institution.

Science and medicine often provide the inspiration for literature, but graduate student Cate Reilly notes that the reverse also can be true. In an effort to establish psychiatry as a legitimate medical science, German physicians in the period from the 1890s to the late 1920s created a standardized terminology, one that eventually formed the basis of our present-day diagnostic manual of mental illness. Reilly, a doctoral student in comparative literature, is exploring how the literary descriptions of mental disorders by Russian and German-language fiction writers contributed to the science of mental illness in ways that stay with us today.

“The story that hasn’t been told is about the birth of these terms and how literature influenced the development of our current international classification system for mental disorders,” Reilly said. “This was all happening at a time of tremendous exchanges between psychiatrists in Germany and Russia. Those nations’ creative writers, some of whom were doctor-physicians like Chekhov, were involved in and contributed to this classification system.”

Reilly was inspired to explore this interdisciplinary area in part by modern debates over the extent to which definitions of pathologies are shaped by culture. At one time, mental illnesses included homosexuality and “indigenous psychopathology,” a diagnosis given by French physicians to native Algerians to justify their subjugation. “Once you have the standardization of these terms, then you start to see their abuse for purposes of power,” Reilly said.

Reilly explores how psychiatry and literature influenced each other during this critical time by citing works by Chekhov, Russian playwright Nikolai Evreinov, and German-language authors Rainer Maria Rilke and Alfred Döblin. For example, Evreinov’s dramas drew themes from German psychology and the anatomical-imaging technologies available during the 1880s and 1890s. Döblin’s 1924 “true-crime” novella, Two Girlfriends Commit Murder by Poisoning, about a court case involving lesbians who plotted to kill their husbands, featured pages of pseudoscientific diagrams to explain the women’s mental states.

“When creative writers influence what happens in psychiatry, it is not so much the case of a specific work of literature influencing a single term or definition, but the opening of a space for experimentation in how mental illness is characterized,” Reilly said. –By Catherine Zandonella

Bright future: Princeton researchers unlock the potential of light to perform previously impossible feats

By Bennett McIntosh

One hundred years ago, Italian chemist Giacomo Ciamician predicted a future society that would run on sunlight.

In a paper presented in 1912 to an international meeting of chemists in New York City, he foresaw a future of vibrant desert communities under “a forest of glass tubes and greenhouses of all sizes” where light-driven chemical reactions would produce not just energy but also wondrous medicines and materials.

Ciamician’s vision has not yet arrived, but a handful of Princeton researchers have succeeded with one part of his legacy: they are harnessing light to perform previously impossible feats of chemistry. In Princeton’s Frick Chemistry Laboratory, blue LED lamps cast light on flask after flask of gently stirring chemicals that are reacting in ways they never have before to create tomorrow’s medicines, solvents, dyes and other industrial chemicals.

The leader in this emerging field is David MacMillan, who arrived in Princeton’s chemistry department in 2006. He was intrigued by the potential for using light to coax new chemical reactions. Like most chemists, he’d spent years learning the rules that govern the interactions of elements such as carbon, oxygen and hydrogen, and then using those rules to fashion new molecules. Could light help change these rules and catalyze reactions that have resisted previous attempts at manipulation?

Changing the rules

The idea for using light as a catalyst had been explored since Ciamician’s time with limited success. Light can excite a molecule to kick loose one or more of its electrons, creating free radicals that are extremely reactive and readily form new bonds with one another. However, most chemists did not think this process could be controlled precisely enough to make a wide variety of precision molecules.

But that changed in the summer of 2007.

MacMillan and postdoctoral researcher David Nicewicz were working on a tough problem. The two scientists wanted to create chemical bonds between one group of atoms, called bromocarbonyls, and another group, known as aldehydes. “It was one of those longstanding challenges in the field,” MacMillan said. “It was one of those reactions that was really useful for making new medicines, but nobody knew how to do it.”

Nicewicz had found a recipe that worked, but it involved using ultraviolet (UV) light. This high-energy form of light causes sunburn by damaging the molecules in the skin, and it also damaged the molecules in the reaction mixture, making the recipe Nicewicz had discovered less useful. MacMillan, who is Princeton’s James S. McDonnell Distinguished University Professor of Chemistry, asked Nicewicz to investigate how to do the transformation without UV light.

Nicewicz recalled some experiments that he’d seen as a graduate student at the University of North Carolina-Chapel Hill. Researchers led by chemistry professor Malcom Forbes had split water into oxygen and hydrogen fuel using visible light and a special molecule, a catalyst containing a metal called ruthenium. The approach was known as “photoredox catalysis” because particles of light, or photons, propel the exchange of electrons in a process called oxidation-reduction, or “redox” for short.

David MacMillan

David MacMillan is a leader in developing the use of light to catalyze chemical reactions — a technique called photoredox catalysis. (Photo by Sameer A. Khan/Fotobuddy)

Visible light is lower in energy than ultraviolet light, so Nicewicz and MacMillan reasoned that the approach might work without damaging the molecules. Indeed, when the researchers added a ruthenium catalyst to the reaction mixture and placed the flask under an ordinary household fluorescent lightbulb, the two scientists were astounded to see the reaction work almost perfectly the first time. “More times than not, the reaction you draw on the board never works,” Nicewicz said. Instead, the reaction produced astonishing amounts of linked molecules with high purity. “I knew right away it was a fantastic result,” he said.

With support from the National Institutes of Health, MacMillan and Nicewicz spent the next year showing that the reaction was useful for many different types of bromocarbonyls and aldehydes, results that the team published in Science in October 2008. Research in the lab quickly expanded beyond this single reaction, and each new reaction hinted at a powerful shift in the rules of organic chemistry. “It just took off like gangbusters,” MacMillan said. “As time goes on you start to realize that there are nine or 10 different things that it can do that you didn’t think of.”

Old catalysts, new tricks

At the time that Nicewicz and MacMillan were making their discovery, chemistry professor Tehshik Yoon and his team at the University of Wisconsin-Madison found that combining the ruthenium catalyst with light produced a different chemical reaction. They published their work in 2008 in the Journal of the American Chemical Society the same day MacMillan’s paper appeared in Science. Within a year of MacMillan publishing his paper, Corey Stephenson, a University of Michigan chemistry professor, and his team found yet another photoredox-based reaction.

With these demonstrations of the versatility of photoredox catalysts, other chemists quickly joined the search for new reactions. About 20 photoredox catalysts were already available for purchase from chemical catalogs due to previous research on watersplitting and energy storage, so researchers could skip the months-long process of building catalysts. However, by designing and tailoring new catalysts, the chemists unlocked the potential to use light to drive numerous new reactions, and today there are more than 400 photoredox catalysts available.

The secret to these catalysts’ ability to drive specific reactions lies in their design. The catalysts consist of a central atom, often a metal atom such as ruthenium or iridium, surrounded by a halo of other atoms. Light frees an electron from the central atom, and the atoms surrounding the center act as a sort of channel that ushers the freed electrons toward the specific atoms that the chemists want to join.

One scientist who became intrigued with the power of photoredox catalysts was Abigail Doyle, a Princeton associate professor of chemistry. Doyle, whose work is funded by the National Institutes of Health, uses nickel to help join two molecules. In 2014, she was searching for a way to conduct a reaction that had long eluded other scientists. She wanted to find a catalyst that could make perhaps the most common bond in organic chemistry — between carbon and hydrogen — reactive enough to couple to another molecule. Perhaps a photocatalyst could make a reactive free radical, allowing her to then bring in a nickel catalyst to attach the carbon-carbon bond.

Abigail Doyle

Abigail Doyle is one of a handful of Princeton professors to quickly adapt the use of blue LED light and photoredox catalysis to rewrite the rules of organic chemistry. Drug companies have taken notice. (Photo by Sameer A. Khan/Fotobuddy)

Unbeknownst to Doyle, the MacMillan lab had recently turned their attention to combining photoredox and nickel catalysts on a similar reaction, coupling molecules at the site of a carboxylate group, a common arrangement of atoms found in biological molecules from vinegar to proteins.

Given the similarities in their findings, the MacMillan and Doyle labs decided to combine their respective expertise in nickel and photoredox chemistry. Together, the teams found a photocatalyst based on the metal iridium that worked with nickel to carry out both coupling reactions — at the carbon-hydrogen bond and at the carboxylate group. Their collaborative paper, published in Science July 25, 2014, showed the extent of photoredox catalysis’ power to couple molecules with these common features.

The ability to combine molecules using natural features such as the carbon-hydrogen bond or the carboxylate group makes photoredox chemistry extremely useful. Often, chemists have to significantly modify a natural molecule to make it reactive enough to easily link to another molecule. One popular reaction — which earned a Nobel Prize in 2010 — requires several steps before two molecules can be linked. Skipping all these steps means a far easier and cheaper reaction — and one that is rapidly being applied.

“It’s one of the fastest-adopted chemistries I’ve seen,” Doyle said. “A couple of months after we published, we were visiting pharmaceutical companies and many of them were using this chemistry.”

The search for new drugs often involves testing vast libraries of molecules for ones that interact with a biological target, like trying thousands of keys to see which ones open a door. Pharmaceutical companies leapt at the chance to quickly and cheaply make many more kinds of molecules for their libraries.

Merck & Co., Inc., a pharmaceutical company with research labs in the Princeton area, was one of the first companies to become interested in using the new approach — and in funding MacMillan’s research.The company donated $5 million to start Princeton’s Merck Center for Catalysis in 2006, and recently announced another $5 million in continued research funding.

In addition to aiding drug discovery, photoredoxcatalyzed reactions can produce new or less expensive fine chemicals for flavorings, perfumes and pesticides, as well as plastic-like polymer materials. And the techniques keep getting cheaper. MacMillan published a paper June 23, 2016, in Science showing that with the aid of a photoredox catalyst, a widely used reaction to make carbon-nitrogen bonds can be carried out with nickel instead of palladium. Because nickel is thousands of times cheaper than palladium, companies hoping to use the reaction were contacting MacMillan before the paper was even published.

Spreading the light

Doyle has continued to explore photoredox chemistry, as have other Princeton faculty members, including two new assistant professors, Robert Knowles and Todd Hyster.

Hyster combines photoredox catalysis with reactions inspired by biology. Drugs often function by fitting in a protein like a hand fits in a glove. But just as placing a left hand in a right glove results in a poor fit, inserting a left-handed molecule into a protein designed for a right-handed molecule will give poor results. Many catalysts produce both the intended product and its mirror image, but by combining photoredox catalysts with artificial proteins, Hyster is finding reactions that can make that distinction.

Hyster, who arrived at Princeton in summer 2015, was drawn to Princeton’s chemistry department in part because of the opportunities to share knowledge and experience with other groups researching photoredox catalysis. “The department is quite collegial, so there’s no barrier when talking to colleagues about projects that are broadly similar,” he said.

Students from different labs chat about their work over lunch, teaching and learning informally — and  formally, as the labs encourage collaboration and sharing expertise, said Emily Corcoran, a postdoctoral researcher who works with MacMillan. When Corcoran was trying to determine exactly how one of her reactions  worked, she was able to consult with students in Knowles’ lab who had experience using sensitive magnetic measurements to find free radicals in the reaction mixture.

“If you have a question, you can just walk down the hall and ask,” Corcoran said. “That really pushes all the labs forward at a faster pace.”

A bright future

After the graduate students go home at night, the blue LEDs continue to drive new chemical reactions and new discoveries. “This is really just the beginning,” Doyle said.

Hyster thinks that within a few years, manufacturers may take advantage of photoredox chemistry to produce biological chemicals — such as insulin and the malaria drug artemisinin — to meet human needs. For his part, MacMillan envisions zero-waste chemical plants in the Nevada desert, driven not by fossil fuels but by the sun.

MacMillan’s vision echoes that of the original photochemist, Ciamician. The Italian’s optimistic vision of a sunlit future is brighter than ever.

Tiny delivery capsules for new drugs

‘Jack’ Hoang Lu researches nanoparticles for drug delivery

Graduate student ‘Jack’ Hoang Lu works on engineering nanoparticles for targeted drug delivery and diagnostics in the laboratory of Robert Prud’homme, professor of chemical and biological engineering. PHOTO BY CATHERINE ZANDONELLA

Some drugs cannot be delivered via a normal pill or injection because they cannot readily dissolve in water. About 40 percent of new pharmaceuticals have this hydrophobic (water-fearing) character, and like a globule of oil in water, they are unable to reach their targets in the body.

Robert Prud’homme, professor of chemical and biological engineering, addresses this problem by putting the drugs inside of nanoparticles, each about one-thousandth of the width of a human hair, which are then covered with a polymer called polyethylene glycol. The small size enables dissolution of the drug to increase their bioavailability.

Nanoparticles can also tackle a different delivery challenge presented by a growing class of drugs called biologics that, as the name implies, are made from cellular or genetic components. The problem is that they are all water-soluble, which make them easy prey for patrolling proteins that identify them as foreign and degrade them. The solution is similar: nanoparticles protect the biologics long enough for them to carry out their mission.

In addition to increasing the time that drugs spend flowing through the body, Prud’homme’s nanoparticles are capable of targeted delivery. This is necessary in the case of toxic drugs, including many cancer treatments, which would damage healthy cells if allowed to roam freely throughout the body. Prud’homme puts appendages, called ligands, on the outside of his nanoparticles that, due to their specific shape and chemical properties, attach to their target and only to their target. In collaboration with Patrick Sinko at Rutgers University, Prud’homme’s group discovered the optimum density of an appendage called a mannose ligand, used to target cells harboring tuberculosis microbes. The unexpected result was that attaching more appendages to a nanoparticle decreased its targeting effectiveness. This demonstration of the complex interplay between engineered nanoparticles and how the human body responds to them is a major theme of the Prud’homme research team. In addition to tuberculosis, the researchers are using these principles to attack cancer, inflammation, and bacterial infections.

The project receives funding from the National Institutes of Health, the National Science Foundation, Princeton’s IP Accelerator Fund and the School of Engineering and Applied Sciences Old Guard Grant.

–By Takim Williams

New chemistry aids drug development

Tova Bergsten


DRUG DEVELOPMENT OFTEN INVOLVES modifying the chemical structure to get the right combination of properties, such as stability and activity. Working in the laboratory of John Groves, the Hugh Stott Taylor Chair of Chemistry, undergraduate Tova Bergsten and graduate student Xiongyi Huang developed a practical and versatile method for altering molecules that could have wide application in drug synthesis and basic research. The method involves using a manganese catalyst to convert carbon-hydrogen bonds into chemical structures known as azides, which are useful for modifying the properties of drugs.

“Since this was my first long-term lab experience, I learned quite a bit,” Bergsten said. “It was eye-opening to be involved in the experimenting, writing and publishing side of a paper. I plan to continue with scientific research, and what I’ve learned through this experience will definitely be useful for my future work.”

The research, which was supported by the National Science Foundation, was published in the Journal of the American Chemical Society on April 14, 2015.

–By Tien Nguyen

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Listening in on bacterial communications

Leah Bushin and Mohammad Syedsayamdost

While an undergraduate, Leah Bushin (left) co-authored an article on the structure of a signaling molecule involved in bacterial communication with co-first author Kelsey Schramma and adviser Mohammad Seyedsayamdost (right), assistant professor of chemistry, PHOTO BY C. TODD REICHART

BACTERIA SPEAK TO ONE ANOTHER using a soundless language known as quorum sensing. In a step toward translating bacterial communications, researchers have revealed the structure and biosynthesis of streptide, a signaling molecule involved in the quorum sensing system common to many diseasecausing streptococci bacteria.

The research team included undergraduate Leah Bushin, who was the co-first author on an article published on April 20, 2015, in Nature Chemistry. Bushin helped determine the structure of streptide as part of her undergraduate senior thesis project.

To explore how bacteria communicate, first she had to grow them, a challenging process in which oxygen had to be rigorously excluded. Next, she isolated the streptide and analyzed it using two-dimensional nuclear magnetic resonance (NMR) spectroscopy, a technique that allows scientists to deduce the connections between atoms.

The experiments revealed that streptide contains an unprecedented crosslink between two unactivated carbons on the amino acids lysine and tryptophan. To figure out how this novel bond was being formed, the researchers took a closer look at the gene cluster that produces streptide. Within the gene cluster, they suspected that a radical S-adenosyl methionine (SAM) enzyme, which they dubbed StrB, could be responsible for this unusual modification.

“Radical SAM enzymes catalyze absolutely amazing chemistries,” said Kelsey Schramma, a graduate student and the other co-first author on the article. The team showed that one of the iron-sulfur clusters reductively activated one molecule of SAM, kicking off a chain of one-electron (radical) reactions that gave rise to the novel carbon-carbon bond.

Kelsey Schramma is a graduate student in chemistry working on a project to study bacterial communication. Disrupting communication could lead to novel strategies to fight infections. PHOTO CREDIT: C. TODD REICHART

Kelsey Schramma is a graduate student in chemistry working on a project to study bacterial communication. Disrupting communication could lead to novel strategies to fight infections. PHOTO CREDIT: C. TODD REICHART

“The synergy between Leah and Kelsey was great,” said Mohammad Seyedsayamdost, an assistant professor of chemistry who led the research, which was supported by the National Institutes of Health. “They expressed interest in complementary aspects of the project, and the whole ended up being greater than the sum of its parts,” he said.

Future work will target streptide’s biological function — its meaning in the bacterial language — as well as confirming its production by other streptococcal bacteria strains.

–By Tien Nguyen

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Unconscious bias: Research helps break down barriers

Stacey Sinclair

Unconscious bias: Research helps break down barriers, PHOTO BY SAMEER A. KHAN/FOTOBUDDY

STACEY SINCLAIR WAS AWARE OF INEQUALITY AT A YOUNG AGE. ”On some level I was always interested in injustice,” said Sinclair, an associate professor of psychology and African American studies. “As a 7-year-old, I wanted to be the first black female to do everything.”

Today, Sinclair uses the tools of science to peel back the human psyche in search of the causes of racial inequality. In a recent study, she and Drew Jacoby-Senghor, who earned his doctorate in 2014, explored how implicit prejudices affected people’s interactions. Since people tend to group together based on shared characteristics, Sinclair and Jacoby-Senghor wondered if people with the same levels of implicit prejudice — also called unconscious bias — end up in the same circles.

The researchers found that whites with stronger implicit anti-black bias were less motivated to affiliate with whites who have black friends than with whites who have white friends. In other words, people likely to have similar levels of implicit prejudice gravitated toward each other, even if they weren’t consciously aware of it. The study was published in the September 2015 issue of the Journal of Personality and Social Psychology.

For the study, the researchers recruited white participants via an online platform and showed them pairs of faces, one white and the other either white or black. In each case, subjects were asked to rate the friendliness of the white face by answering questions such as, “To what extent do you think you would want to become friends with this person?” Additionally, the subjects’ perceived similarity between themselves and the person on the screen was measured by asking how strongly they agreed with statements such as, “This person and I probably see things in much the same way.”

Sinclair and her collaborators found that white participants with higher implicit bias exhibited higher perceived similarity to the white faces paired with a white friend. This perceived similarity in turn was related to a stronger desire for friendship.

Sinclair’s previous research shows that people adjust their implicit-prejudice level to match the views of the people with whom they interact, a principle called social tuning. This research, which Sinclair outlined in a 2014 review article in the journal Policy Insights from the Behavioral and Brain Sciences, suggests that egalitarian views can be catching.

Sinclair offers some practical advice based on her research. To make use of social tuning, she advises: “Literally wear your egalitarianism on your sleeve. In policy, what this means is make it clear that this is an environment that truly appreciates diversity, that equality is a value that the individuals in this environment hold. Our research suggests that people’s attitudes will change to be in line with these values relatively effortlessly on their part.”

In awareness of their tendency to seek similarity, Sinclair suggests that people step out of their comfort zone. “When you’re networking, or when you’re at a party, and you’re deciding who to walk up to, if your impulse tells you to go one way, go the other way. If we all did that, it could really change what our networks look like.”

–By Takim Williams

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Janet Currie investigates the building blocks of children’s success

Janet Currie


By Michael Hotchkiss

TRAINED AS A LABOR ECONOMIST, Janet Currie earned her doctorate at Princeton by studying strikes and arbitration. But as she began her academic career in the late 1980s, she shifted her focus to examining the building blocks of success for children, as well as the stumbling blocks that can get in their way.

While the topics are very different, Currie said both benefit from research by economists. “I realized that economics is really more of a method, or a way of thinking, than a set of topics, and I have implemented that by working on issues that can benefit from the tools of economics research,” she said.

Over the nearly three decades since, Currie has used the methods of an economist, her analytical skills and an openness to new ideas to offer important insights into the health and well-being of children. In the terms of economics, she studies the factors that affect children’s human capital — the intangible assets such as health, skills and knowledge that play a role in life outcomes.

Today the Henry Putnam Professor of Economics and Public Affairs at Princeton and chair of the Department of Economics, Currie has tackled research on a wide range of topics, including socioeconomic differences in child health, environmental threats to children’s health and the long-term effects of poor health in early childhood.

Beyond the individual findings, Currie said, are broader lessons.

“One would be that very early life is important,” she said. “That is now pretty well accepted and has had an impact on policy, but at the time I was starting to do this research that wasn’t so widely appreciated. Another kind of general conclusion is that pollution at lower levels than Environmental Protection Agency thresholds for concern has measureable and detectable health effects.”

Currie joined the Princeton faculty in 2011 from Columbia University. Previously, she was on the faculty at the University of California-Los Angeles and the Massachusetts Institute of Technology.

At Princeton, Currie is director of the Center for Health and Wellbeing, which fosters research and teaching on aspects of health and well-being in developed and developing countries. She is also a senior editor of the Future of Children, a publica- tion that translates social science research about children and youth into information that is useful to policymakers, practitioners and other nonacademic audiences.

Sara McLanahan, a Princeton sociologist who works with Currie on projects including the Future of Children and shares many of her research interests, said Currie is “one of the most outstanding economists in the country who is doing work on child health.” And, McLanahan added, Currie’s impact goes beyond her research.

“She’s just very willing to give her time and be generous,” said McLanahan, the William S. Tod Professor of Sociology and Public Affairs. “She’s a straight shooter. She tells you what she thinks. She does more than her share, and she wants it to be done right. She’s just a great positive force.”

An economist’s approach

Currie, who earned her bachelor’s and master’s degrees in economics from the University of Toronto before coming to Princeton for her doctoral studies, said several aspects of economics make it useful in studying children and their outcomes.

Among them: a tradition of using models to frame issues, an emphasis on measurement and a focus on establishing causal relationships.

Often, she has applied these principles in natural experiments, which are observational studies where conditions outside a researcher’s control randomly assign some people to an experimental condition and others to a control condition.

For example, interest in the impact of pollution on infant health led Currie and Reed Walker, then a graduate student at Columbia and now an assistant professor at the Haas School of Business at the University of California-Berkeley, to examine the effect of introducing electronic toll collection on the health of children born to mothers who lived near toll plazas. They found that the switch to electronic toll collection, which greatly reduced traffic congestion and vehicle emissions near toll plazas, was associated with a decline in premature and low-birth-weight babies born to those mothers.

That research depended on identifying the roll-out of electronic toll collection as a potential natural experiment, gathering pollution data for the area of toll plazas, and mining birth records for the necessary information about the residences of mothers and birth outcomes.

In another natural experiment, Currie and Maya Rossin-Slater of Columbia used birth records from Texas and meteorological information to identify children born in the state between 1996 and 2008 whose mothers were in the path of a major tropical storm or hurricane during pregnancy. They found that expectant mothers who dealt with the strain of a hurricane or major tropical storm passing nearby during their pregnancy had children who were at elevated risk for abnormal health conditions at birth.

Keeping an open mind

Hannes Schwandt, who has worked closely with Currie during three years as a postdoctoral research associate at the Center for Health and Wellbeing, said another important aspect of Currie and her work is her openness to new ideas.

“On the one hand, she has this great detailed expertise, given all the work she has done,” Schwandt said. “At the same time, she’s always open to new questions. I think combining her expertise with this view for broad, new directions is what makes her so special.”

Take a paper he and Currie published in 2014 on the effect of recessions on fertility. The idea began, Schwandt said, with a discussion they had about evidence that babies born during recessions are generally healthier than those born in better times.

“Janet said we need to step back and look at fertility — who is giving birth — instead of focusing on the health of babies,” Schwandt said. “She immediately made the connection that in the news there is always a discussion that there is decline in fertility during recessions. But no one really knew the long-term effect.”

After examining 140 million births over 40 years, Currie and Schwandt found that recessions are linked to an increase in the number of women who remain childless at age 40.

What’s ahead

Currie is continuing to pursue ways to address issues relating to children and their development.

One project is looking for new evidence of the impact of lead exposure on children and their educational outcomes in Rhode Island. By matching birth records, lead-test results and school records, Currie is examining the impact of a program to reduce children’s exposure to lead.

“One of the really interesting things about this research, I think, is that the program to reduce lead exposure seems to have been pretty effective,” Currie said.

Because African American children were more likely to live in areas with high lead levels, the program brought their lead levels down more quickly than those of white children. At the same time, Currie said, the gap in standardized test scores between the groups narrowed.

The research could offer new clues about the role lead exposure plays in the lower test scores typically recorded by students who live in inner-city areas where lead exposure is more common, Currie said.

Another work in progress takes advantage of the implementation of congestion pricing in Stockholm, which levies a tax on most vehicles entering and exiting the city’s center, to measure the impact of traffic — and the resulting pollution — on child health. A third is examining state-by-state differences in smoking patterns among pregnant women and the relationship between smoking among pregnant women and low-birth-weight births.

A topic she would like to address in future work: mental health.

“I’m interested in that for a lot of different reasons,” she said. “If you look at the U.S. economy, mental health is the leading cause of lost work. That’s because it tends to strike people who are of working age, whereas a lot of other health conditions are more for older people. It’s important from an economic point of view. It also seems to be very related to a lot of learning issues.”

Over the past 20 years, Currie said, a raft of new psychiatric medications has come on the market, many of which are not well understood, and prices are rising.

“It seems like there’s this huge black box of things that are happening and no one is really studying, and there’s not very good data on it,” she said. “That’s something I’ve been struggling with for a while, how to get some purchase on that problem.”

Valued as a mentor

Currie is also widely recognized for her work with young researchers and her advocacy for them.

“In addition to all the work she does as a top economist, being willing to work with students is a great benefit,” McLanahan said. “Having someone do so well and be so generous is important, especially for the next generation of female economists.”

In spring 2015, Currie received a Graduate Mentoring Award from the McGraw Center for Teaching and Learning. Graduate students described Currie as insightful and readily available to help aspiring researchers develop their ideas and present them publicly.

Molly Schnell, a Ph.D. candidate in economics, said Currie is so generous with her time “that she seems to defy the principle of scarcity.”

In particular, she pointed to Currie’s willingness to co-author papers with graduate students.

“Learning to develop a paper by working through the process with an established researcher is a formative experience, and Janet makes sure that her students have this opportunity,” Schnell said.

Schwandt said Currie has helped him grow more confident in tackling new topics.

“One thing I’ve learned from her is not to worry too much whether other people think something is economics or not,” he said. “She always says: ‘First, who defines what economics is? And second, why do we really care so long as it is a really important question and we can help answer it?’”

Professor Janet Currie’s research uses the tools of economics research to study issues in children’s health. Among her findings:

E-Z Pass Research


Expectant mothers



Foreclosure research




Fertility research





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RESILIENT SHORES: After Sandy, climate scientists and architects explore how to co-exist with rising tides

Coastal Resilience
AFTER THE WIND, RAIN AND WAVES of Hurricane Sandy subsided, many of the modest homes in the Chelsea Heights section of Atlantic City, New Jersey, were filled to their windows with murky water. Residents returned to find roads inundated by the storm surge. Some maneuvered through the streets by boat.

This mode of transport could become more common in neighborhoods like Chelsea Heights as coastal planners rethink how to cope with the increasing risk of hurricane-induced flooding over the coming decades. Rather than seeking to defend buildings and infrastructure from storm surges, a team of architects and climate scientists is exploring a new vision, with an emphasis on living with rising waters. “Every house will be a waterfront house,” said Princeton Associate Professor of Architecture Paul Lewis. “We’re trying to find a way that canals can work their way through and connect each house, so that kayaks and other small boats are able to navigate through the water.”

The researchers aim for no less than a reinvention of flood hazard planning for the East Coast. A new approach, led by Princeton Professor of Architecture Guy Nordenson, rejects the strict dividing line between land and water that coastal planners historically have imposed, favoring the development of “amphibious suburbs” and landscapes that can tolerate periodic floods. These resilient designs can be readily modified as technologies, conditions and climate predictions change.

Discovery2014_CR_textbox1To plan for future flood risks, Princeton climate scientists are using mathematical models of hurricanes to predict storm surge levels over the next century, taking into account the effects of sea level rise at different locations. Four design teams — from Princeton, Harvard University, the City College of New York and the University of Pennsylvania — are using these projections to guide resilience plans for specific sites along the coast: Atlantic City; Narragansett Bay in Rhode Island; New York City’s Jamaica Bay; and Norfolk, Virginia. [See Planning for resilience up and down the coast.]

The designs will serve as a guide for the U.S. Army Corps of Engineers’ North Atlantic Coast Comprehensive Study, a plan to reduce the risk of flood damage to coastal communities, which is due to Congress in January 2015. “The Army Corps understands that they have to revisit what it means to make structures that are resilient,” said Enrique Ramirez, a postdoctoral research associate in architecture at Princeton and the project’s manager. He serves as a liaison between the design teams and Army Corps officials in regional districts.

The idea for the project grew out of Nordenson’s work on a pre-Sandy project to develop creative proposals for adaptation to rising sea levels in New York Harbor. The project culminated in a book, On the Water: Palisade Bay, and a 2010 exhibition, Rising Currents, at the New York City Museum of Modern Art. The proposals included repairing and lengthening existing piers, as well as planting wetlands and building up small islands inside the harbor. “It was forward thinking because we showed that there are benefits to building things in the water,” Nordenson said. Other Princeton contributors to On the Water were engineering professors James Smith and Ning Lin (then a graduate student) and climate scientist Michael Oppenheimer of the Woodrow Wilson School of Public and International Affairs.

Hurricane Sandy heightened the urgency of long-term coastal planning. While advising a New York State commission on future land use strategies, Nordenson began discussing a broader plan for the East Coast with Joseph Vietri of the U.S. Army Corps of Engineers and Nancy Kete of the Rockefeller Foundation. This discussion led to the Structures of Coastal Resilience project, which is funded by the Rockefeller Foundation and began in October 2013. The project is managed by Princeton’s Andlinger Center for Energy and the Environment and will extend resilient design concepts to other coastal regions, as well as integrate hurricane storm surge predictions with projections of local sea level rise.

One of the project’s goals is to encourage a reconsideration of the absolute flood zone boundaries on maps produced by the Federal Emergency Management Agency (FEMA), which determine building code requirements and insurance rates. Climate science shows that the geographical borders of flood risk should be based on the probabilities and outcomes of different storm events, not the placements of artificial levees that may be overtopped by high storm surges. Indeed, many of the homes and businesses ravaged by Hurricane Sandy were not located in flood hazard zones on FEMA’s maps. “Sandy really brought home the message that we have to do a lot better in the future,” said Oppenheimer, the Albert G. Milbank Professor of Geosciences and International Affairs. “Because while we sit here thinking about it, the risk is only increasing.”

Click to enlarge. The low-lying barrier island that is home to Atlantic City is particularly vulnerable to storm surges, especially in parts of the city, such as residential Chelsea Heights, that were built on wetlands. Researchers are exploring ways to make existing neighborhoods (Panel A) more resilient in the face of occasional storm surges. By raising houses, using roads as low levees and letting abandoned lots return to wetland conditions, these neighborhoods can become “amphibious suburbs” (Panel B). A similar approach can be applied to existing canal neighborhoods (Panel C), making them more resilient and tolerant of flooding (Panel D).

Click to enlarge. The low-lying barrier island that is home to Atlantic City is particularly vulnerable to storm surges, especially in parts of the city, such as residential Chelsea Heights, that were built on wetlands. Researchers are exploring ways to make existing neighborhoods (Panel A) more resilient in the face of occasional storm surges. By raising houses, using roads as low levees and letting abandoned lots return to wetland conditions, these neighborhoods can become “amphibious suburbs” (Panel B). A similar approach can be applied to existing canal neighborhoods (Panel C), making them more resilient and tolerant of flooding (Panel D).

Smarter building codes are also needed, according to Lin, an assistant professor of civil and environmental engineering, who heads the effort to predict storm surge levels. Current building code books primarily address earthquake risks. “A tiny few chapters are for wind, and very few pages are for flooding,” Lin said. Large-scale, long-term projects such as levees and seawalls have been the standard approach to coastal protection. But the Coastal Resilience team puts forth a different view, one of coping with occasional flooding rather than fighting it. “We will never be able to prevent such hazards. We can only be prepared to reduce their impact,” Lin said.

Resilient designs call for supporting, revitalizing and in some cases reengineering natural features such as wetlands and beach dunes. This so-called “soft infrastructure” can reduce the impact of waves, improve water quality and create new recreational spaces for coastal residents and visitors. Rather than the exclusive construction of barriers, the project’s plans include “layered systems of natural and engineered structures that will respond in different ways to different hazards,” Nordenson said. “It is a more nuanced and more resilient approach.”

Flexible design is also an important component of the project. Ideally, the sizes and arrangements of structures will be adaptable as predictive models improve. Scientists continue to debate how climate change will affect the strength and frequency of storms. “But we are trying to take what we know right now and do the best job we can in accounting for the uncertainties in what we know, and use that to explore how we should be thinking about adaptation,” said Smith, the William and Edna Macaleer Professor of Engineering and Applied Science and chair of the Department of Civil and Environmental Engineering at Princeton.

Meteorological measurements show that the extreme winds of a swirling hurricane transfer energy to the ocean surface. The winds and the storm’s low air pressure cause a dome of water to rise, generating a surge of high water when the storm makes landfall. “When you think of the storm, you think of the wind and the rain. That’s what seems scary,” said Talea Mayo, a postdoctoral research associate who is working with Lin to model storm surges. But the coastal storm surge was the main cause of deaths and property damages from Hurricane Sandy.

To predict future storm surges, Lin and Mayo are using thousands of synthetic hurricanes modeled by Kerry Emanuel, an atmospheric scientist at the Massachusetts Institute of Technology. “Anytime you’re studying hurricanes, especially so far north, your historical data are really limited because there just aren’t enough events,” Mayo said. “So instead of basing our risk analysis on historical data, we use synthetic data.”

Hurricane damage 1944

Storms have caused significant damage to Atlantic City’s iconic boardwalk throughout its existence. Shown here is South Inlet during the Great Atlantic Hurricane of 1944. Image from the archive of the Coastal and Hydraulics Laboratory, Engineer Research and Development Center, Vicksburg.

Emanuel’s team uses existing models of global climate circulation patterns to generate 3,000 synthetic, physically possible storms for nine different climate change scenarios at each of the four study sites — a total of more than 100,000 storms. These hurricanes exist only in computer code, but their wind speeds, air pressure levels and patterns of movement are based on physical laws and information from recorded storms. Mayo and Lin plug these parameters into algorithms that work like sophisticated versions of high school physics problems: solve the equations for conservation of mass and momentum to estimate maximum water levels at each site. Variations in tide levels, coastline shapes and seafloor topographies add additional layers of complexity.

To make reasonable projections of future flood hazards, the models must also account for sea level rise. According to geoscientist Chris Little, an associate research scholar working with Oppenheimer, storm surges are a short-term version of sea level rise. “They both contribute to coastal flooding,” Little said. “Climate change will be felt through the superposition of changes in long- and short-term variations in sea level.”

And when it comes to sea level rise, local projections are crucial for planning efforts. A constellation of factors influence regional differences in sea levels, including the vertical movement of the Earth’s surface, changes in ocean circulation and the melting of glacial ice. Little and Oppenheimer were among the authors of a study published in June 2014 in the journal Earth’s Future, which used model-based and historical tide gauge data for sites around the globe to project local sea levels over the next two centuries.

“We live in a hotspot, where the local sea level rise has been higher in the past than the global mean, and we expect it to continue to be higher in the future,” Oppenheimer said — as much as 40 percent higher than the worldwide average. One reason for this is that the land along the East Coast is slowly sinking (by a millimeter or two each year), a legacy of the ice sheet that covered much of North America until about 12,000 years ago. The ice sheet depressed Earth’s crust over present-day Canada, causing the liquid mantle beneath to bulge southward. Now that the glaciers have melted, the mantle is being gradually redistributed, flowing out from under the East Coast of the United States.

Sea levels respond slowly to changes in climate, including the current warming trend, caused in part by increased carbon dioxide levels from human activity. Because future carbon emissions depend on human decisions, predictions of sea level rise come with built-in uncertainty. This project attempts to meet this challenge head-on: “A major purpose of the project is to think about doing a more thorough job of assessing the uncertainty in these flood zones,” Little said. “I think it’s difficult but worthwhile.”

Resilient designs call for planning and reengineering natural features such as salt marshes, submerged aquatic vegetation and wetlands, as in this imagined coastline for Staten Island, south of Manhattan.

Resilient designs call for planning and reengineering natural features such as salt marshes, submerged aquatic vegetation and wetlands, as in this imagined coastline for Staten Island, south of Manhattan.

Because of this uncertainty, climate scientists deal in probabilities. The Princeton team has projected flood levels for storms with return periods of 100, 500 and 2,500 years. A return period of 100 years is akin to a “100-year flood” — this means that in any given year there is a 1 percent chance of that flood level occurring. These forecasted flood risks are key to making smart building and design decisions in the face of climate change. “Every decision-maker is going to look and decide what risk is tolerable for their region in the context of how much it would cost to defend against that risk,” Oppenheimer said.

The design teams are beginning to test their plans against the climate scientists’ predictions. Simulated local water levels will reveal which structures may be inundated by future storms and at what probabilities. These analyses may prompt the designers to adjust the heights of buildings, roads or beach dunes in their blueprints. And as the science improves, this process will repeat itself. “Over time, others can start to add things that we haven’t been able to include, like the relationship of the wind and the flood,” Nordenson said.

True resilience necessitates a change in outlook. In Atlantic City, the focus area for Lewis and the Princeton group, a narrow channel of water separates the Chelsea Heights neighborhood from the city’s famous boardwalk and high-rise casinos, where many residents work. “You have extensive areas of suburban neighborhoods that are built on wetlands,” said Lewis. “Two binary positions are retreat, where you return these to wetlands, and fortification, which is the seawall approach. And both of them are problematic.”

The team recognizes the social and economic importance of maintaining the neighborhood. But barricading it behind a seawall may be prohibitively expensive, not to mention unattractive. More important, metal or concrete seawalls can actually exacerbate flooding when areas behind them are inundated by heavy rain. Lewis and his team have a fundamentally different vision for places like Chelsea Heights: “We’re looking at developing an amphibious suburb,” he said. “We want water to come in. If there are berms [earthen seawalls] that are put in, they should be built with a series of valves.”

The plans for Chelsea Heights include raised homes and roads interspersed with canals and revitalized wetlands. Lewis hopes these ideas will be useful to policymakers and to the Army Corps of Engineers, which may apply the Princeton team’s concepts to Chelsea Heights and other similar communities along the New Jersey shore. By the end of this century, grassy suburban lawns may be transformed into salt marshes.


Natural features play a pivotal role in the designs for two of the project’s other focal regions, New York’s Jamaica Bay and Rhode Island’s Narragansett Bay.

  • The plan for Jamaica Bay includes the use of local dredged materials to build up land for marsh terraces, which can serve to reduce wind fetch as well as improve water quality and encourage sediment deposition, according to Catherine Seavitt, an associate professor of landscape architecture at the City College of New York. In particular, her team hopes to expand the restoration of a native wetland grass, Spartina alterniflora, an effective attenuator of wind and waves that also provides valuable ecological habitat.
  • Michael Van Valkenburgh and Rosetta Elkin lead the Harvard design effort for Narragansett Bay. One of their plans involves relocating two critical reservoirs that supply drinking water to the city of Newport. The reservoirs are currently vulnerable to coastal flooding; the proposed project would use dredged material from the original reservoir to fill in and extend the existing maritime forest, now a rare ecosystem along the New England coast. The larger forest, designed by the team, would mitigate coastal erosion, attenuate wave action, and become a valuable recreational area for surrounding communities.
  • The project’s other site, the Norfolk, Virginia, area of Chesapeake Bay, calls for a more extensive reshuffling of settlement and infrastructure, according to Dilip da Cunha, an adjunct professor of landscape architecture at the University of Pennsylvania. Of the four sites, Norfolk is expected to see the most dramatic sea level rise, and is home to the world’s largest naval station and a vital commercial port. The UPenn team’s designs stem from the natural network of fractal-like interfaces where land and water meet. The plan seeks to bolster “fingers of higher ground” that will be more robust to gradual sea level rise as well as storm surges. “The higher grounds could be for housing, schools and other facilities, and the low grounds could accommodate various things, from marsh grasses to football fields,” da Cunha said. “Things that can take water in the case of a storm event, but will not endanger lives.”

-By Molly Sharlach