Bioengineering: Unlocking the secrets of human health

Bioengineering cover imageBy Takim Williams

RED-HOT RIVERS OF MOLTEN COPPER and aluminum alloys streamed from one receptacle to another. As an undergraduate watching the demonstration in a materials science class, Clifford Brangwynne was reminded of cells migrating through the bloodstream. He realized at that moment that he could mold his interest in materials science and engineering into work that might ultimately have implications for human health.

Bioengineering blood vessel imageScientists like Brangwynne, now an assistant professor of chemical and biological engineering at Princeton, recognize the natural connection between engineering and the life sciences. Their research is setting the groundwork for future applications in health and medicine, including curing diseases such as Alzheimer’s, growing replacement organs and preventing developmental abnormalities. Each of these pursuits hinges on the understanding that living matter obeys the same principles as nonliving matter.

Discovering the relevant principles — and using them to manipulate biological systems to meet our needs — is the goal of the growing field of bioengineering. “The thing that we do that’s different from other scientists who are looking at states of matter and their properties is that we are doing it in the context of living cells,” Brangwynne said. “What is the state of matter inside of a cell and how does that enable biological function?”

Brangwynne gestures toward a can of Gillette shaving foam next to a cylinder of silly putty on his desk and explains that the familiar grade school schema of three states of matter — solid, liquid, gas — is not entirely accurate. There are phases in between, and combinations with their own surprising properties.

“A mound of foam is essentially a solid,” Brangwynne said. “You can push on it and it deforms, and when you take your finger away it springs back into shape. You’ve taken something that is 95 percent gas — it’s mostly air — and 5 percent liquid, and you’ve combined those in such a way that you get a solid.”

Correct biological function depends on transitions between these phases of matter. For example, your blood — typically a free-flowing liquid — clots to form a protective scab. However, these transitions can cause problems, for instance when an internal blood clot causes a stroke.

Likewise, the liquid inside each cell — the cytoplasm — regularly goes through local phase transitions, some of which are disruptive. This issue is linked to neurodegenerative diseases, including Alzheimer’s disease and amyotrophic lateral sclerosis (Lou Gehrig’s disease). In these cases, proteins aggregate and spontaneously transition from a liquid phase into a sticky, solid-like state, prohibiting normal function in the brain or nervous system. These phase transitions are also thought to be involved in controlling cell size and growth, and thus diseases such as cancer.

Nucleoli from amphibian egg cells

Researchers in the Brangwynne lab use nucleoli from amphibian egg cells to study the role of gravity in determining the size of living cells. IMAGE COURTESY OF CLIFFORD BRANGWYNNE LAB

Brangwynne’s research focuses on gaining a better understanding of these living states of matter, and how they can be manipulated. Over the past few years, his group has published several studies exploring the molecules that control intracellular phase transitions and how the living matter within a cell affects gene regulation and cell size.

In one particularly exciting study, graduate student Marina Feric discovered that liquid-phase droplets of RNA and protein are biophysically linked to cell size through the force of gravity. Brangwynne, who receives support from the National Science Foundation (NSF) and the National Institutes of Health (NIH), is optimistic that these fundamental studies will lead to medical applications. “We’re certainly hoping to use our findings to perturb these systems and keep cells in a healthier state,” he said.

Swimming upstream

Like Brangwynne, Professor Howard Stone followed the flow of ideas from an area of engineering — fluid mechanics — to biology. “The living world involves flow almost by definition,” said Stone, who is the Donald R. Dixon ’69 and Elizabeth W. Dixon Professor of Mechanical and Aerospace Engineering. “You circulate blood, you breathe streams of air in and out, you sweat to regulate temperature. If you study fluid mechanics, and if you’re somewhat open-minded, it’s easy to stumble across biological problems.”

One of the biological problems that caught Stone’s attention is how bacteria move in a fluid. Moving through water is far more difficult for bacteria than it is for a human. For single-celled creatures a millionth of a meter long, the force of friction dominates their ability to swim in a given direction. Instead, bacteria are usually just carried along for the ride.

Image of lungs

“The living world involves flow almost by definition.” –Howard Stone, the Donald R. Dixon ’69 and Elizabeth W. Dixon Professor of Mechanical and Aerospace Engineering

The dominance of friction led to a discovery in Stone’s lab four years ago by visiting graduate student Yi Shen, who found that P. aeruginosa, a dangerous pathogen sometimes found in hospitals, can move against a current. The bacterium loses its flagellum — a long tail for swimming — when it adheres to a surface, which for many cells dictates the end of mobility. Yet P. aeruginosa can drag itself along a wall of, for example, a branched medical tube, by its small, tentacle-like pili, which are strong enough to resist the force of friction.

After observing this phenomenon, Stone and his collaborators — Professor of Molecular Biology Zemer Gitai; Albert Siryaporn, an associate research scholar in molecular biology; and Kevin Minyoun Kim, a graduate student in chemistry — began researching this behavior in systems mimicking the human body.

“Your blood vessels have branches. Your lungs are branched. We’ve made model branched systems and used a pump — like a heart — to drive fluid through it,” Stone said. “Bacteria inoculated into this flow sometimes end up in places you wouldn’t expect, and that, at this time, a simulation would never predict.” This basic research, which is supported by NSF, may allow us to better anticipate the movements of pathogens — in our bodies or our environments — in order to prevent infection and contamination.

Fluid environment

Bacteria are single-celled organisms that can form colonies, but a more sophisticated arrangement occurs in our own bodies, where huge communities of cells organize into tissues and organs. Celeste Nelson, an associate professor of chemical and biological engineering, studies the fetal development of these organs, which depends on the fluid environment in which they form.

One of the organs that forms in a fluid environment is the lung. A fetus’s lungs are filled with fluid during gestation. Nelson uses tissue cultures — parts of organs grown in laboratory dishes — and manipulates the speed and pressure of tiny streams of liquid that are directed onto the growing lung cells by small tubes.

Nelson has discovered that the higher the pressure of this fluid in the fetal lung, the more quickly the lungs develop, whereas lower pressure leads to slower development. Several congenital disorders can derail lung development, and Nelson’s work — which is supported by NIH, NSF, the David and Lucile Packard Foundation, the Camille and Henry Dreyfus Foundation, the Burroughs Wellcome Fund, the Essig Enright Family Foundation, and Princeton’s Project X, which provides seed funding for unconventional research — may improve our ability to diagnose such problems early.

The lungs, kidneys, mammary glands and other organs develop through a branched structure, which is an efficient space-filling strategy for functions that require maximum surface area. This exponential branching pattern is a highly reproducible selfassembly process, and in Nelson’s opinion, the forest of alveoli in the lungs is the most beautiful example. “The 23 generations of branches means several hundred million paths,” said Nelson. “Every one of those paths is needed for efficient diffusion of oxygen into the infant blood stream immediately after birth. “What’s amazing,” she said, “is that all of the branches in my lungs look exactly like the branches in your lungs.”

Lung image

Lung tissue extracted from a reptile embryo helps the Nelson lab study the effect of the fluid environment on lung development.

Nelson’s lab also studies a behavior in cancer cells called reversion, which — if it could be induced — would turn many cancers into benign, treatable illnesses. She collaborates with Derek Radisky, a researcher at the Mayo Clinic in Jacksonville, Florida. For Nelson, who started studying breast cancer while a postdoctoral fellow, the body’s organ systems have a mechanical elegance.

Timing is everything

Stanislav Shvartsman is as fascinated by the chemical aspects of development as Nelson is by the mechanical aspects. His research focuses on embryogenesis, the very early stages of fetal development.

“When you want to bake a cake, it’s not enough to say that you need eggs and milk and flour,” said Shvartsman, a professor of chemical and biological engineering and the Lewis-Sigler Institute for Integrative Genomics. “Knowing the ingredients, and even knowing the sequence in which you add these ingredients — which is what we know from genetics — is not enough to bake a cake that tastes good.”

When the recipe — the proper quantities of chemicals released by the cells of the embryo at the proper times — isn’t followed exactly, there are consequences for the developing organism. For example, a large class of developmental abnormalities, known as RAS-opathies, is associated with asymmetry in the craniofacial complex, stunted height, congenital heart defects, developmental delays and other issues. Such defects are observed in one in every thousand births and are believed to be caused by mutations in genes of the Ras-MAPK pathway.

Biologists know which genes are mutated, and even where to find these genes on our DNA. What they don’t know is why these particular mutations lead to a distinct set of clinical features. To find out, researchers turn to organisms that macroscopically look very different from us — such as bacteria and worms — but are very similar at the cellular level. Shvartsman’s research group, which is supported by NIH and NSF, uses the fruit fly to study embryogenesis.

Initially, the handful of cells that make up an embryo are all identical. By the time of birth, that homogenous handful will have given rise to brain, nerve, heart, blood and every other kind of cell required for a living, breathing organism. In order to differentiate into the right kind of cell at the right time, and to arrange into the correct three-dimensional shape, the embryonic cells have to communicate. They speak to each other through a language of chemical signals.

The signals are actually protein molecules, Shvartsman said. A protein released by one cell attaches to a receptor protein embedded in the surface of a neighboring cell. That surface protein reacts by changing shape, and in turn changing the internal environment of its cell. In this way cells “hear” each other. At any given time multiple cells are releasing various proteins, and the combination of signals floating through the embryonic environment tells a cell what to become, or when to divide to make more of itself.

To crack the code, Shvartsman is looking at one signal at a time, beginning with a set of proteins that is well understood genetically thanks to the work of such Princeton biologists as Gertrud Schüpbach, the Henry Fairfield Osborn Professor of Biology. By controlling the amount of these proteins released in the fly embryo, Bomyi Lim, a former graduate student in Shvartsman’s lab and now a postdoctoral research associate at the Lewis-Sigler Institute for Integrative Genomics, has discovered the minimum dosage necessary for proper structural development. This is the first step in a long process, but it is a milestone, and Shvartsman is excited about continuing the process. “It’s very exciting to work in a field where there’s no risk of ever saying, ‘This is the end of the times-table. There is no more material to learn,’” he said.

Image of fruit fly embryo structure

The image shows thin slices of a part of fruit fly embryos where stem cells turn into mature eggs. Created by graduate students Yogesh Goyal and Bomyi Lim and postdoctoral researcher Miriam Osterfield in the laboratory of Stanislav Shvartzman, the image was selected for display in Princeton’s 2014 Art of Science competition.

Some assembly required

Brangwynne views embryogenesis as the epitome of self-assembly, the process by which small, disorganized components interact based on simple rules to form complex structures without human intervention. A classic example is the snowflake, a delicate crystalline jewel formed in midair as water molecules freeze. Engineers have been trying to take advantage of self-assembly for some time — often in Brangwynne’s field of materials science — where time and money could be saved if certain synthetic materials would form on their own in a solution, rather than being painstakingly put together atom by atom.

“The embryo of an organism like C. elegans essentially starts out as just a bag of molecules,” Brangwynne said. Once the egg is fertilized, it begins to organize, and the unstructured soup of molecules turns into a wriggling worm. “There’s absolutely nothing that human engineering can do that comes anywhere close to what I just described takes place in embryos all the time,” Brangwynne said.

While Princeton scientists are importing methods and paradigms from engineering disciplines to biology, they see a two-way street, recognizing that biology itself has methods to share.

“We would like to learn how nature, through hundreds of millions of years of evolution, has generated these systems that are just completely unbelievable in their level of sophistication,” Brangwynne said. “It’s as if we’ve been visited by an alien civilization that was millions of years more advanced than us. The first thing we would do would be to take a really close look at that spaceship. We’d try to figure out what it is made of, what are the principles that govern its flight and its control systems. That’s what we are doing with biological systems.”

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Beautiful minds

Princeton’s mathematicians explore the hidden patterns that underlie nature and form the basis of modern technologies

By Catherine Zandonella

TOWERING ABOVE THE ARCHES AND IVY, 13-story Fine Hall is home to the Department of Mathematics and to some of the deepest thinkers on campus.

“Our goal as a department is to work on the most fundamental problems, to address the most interesting questions, to open new directions of inquiry, and to push the frontiers of mathematics. It is that simple,” said David Gabai, the Hughes- Rogers Professor of Mathematics and chair of the department since 2012.

It is a goal that Princeton has met for more than a century. It was here in the late 1930s that Alan Turing — subject of the 2014 film The Imitation Game — earned his Ph.D. and worked on ideas that form the foundation of computer science. In the 1990s at Princeton, Andrew Wiles conquered one of math’s toughest challenges by proving Fermat’s Last Theorem, a problem that had baffled mathematicians for three centuries. It was at Princeton that John Nash, his life also made into a film, A Beautiful Mind, did some of his most influential work in mathematics.

Today’s mathematics department carries on this tradition of excellence. Graduate students of the program at Princeton have gone on to become professors at the top universities in the country and abroad. “The combination of freedom to explore what interests you and exposure to some of the most renowned faculty in the field makes Princeton’s one of the best programs for training new researchers,” said Igor Rodnianski, professor of mathematics and acting chair of the department.

The number of Princeton undergraduates choosing math has tripled in the past 15 years, said Rodnianski. “People are starting to understand that mathematics is one of the foundational sciences, and that getting an undergraduate education in math will be helpful no matter what you do afterwards.”

Science of patterns

Mathematics is often described as the science of finding patterns, which appear throughout nature, in everything from ripples of pond water to the orbits of the planets. The patterns found in the numbers we use every day (1, 2, 3 …) have fascinated mathematicians since the time of the ancient Greeks. In the last few centuries, mathematics research has led to discoveries about the underlying structure of nature and fueled the development of today’s technologies.

“A lot of people think that mathematics is a rigid science, that we just sit around applying existing problem-solving tools — like addition, subtraction, multiplication and division — to problems that are given to us,” Rodnianski said. “Well, neither are the problems given to us, nor are we given the tools. We have to develop the tools as we go along.”

The creative nature of mathematics research makes its pursuit rewarding in its own right, according to many of the Princeton mathematicians interviewed for this article. Often the applications of this research take decades to emerge, but when they do, they are transformative. “Mathematical concepts can have dramatic consequences in other fields,” said Elias Stein, the Albert Baldwin Dod Professor of Mathematics, Emeritus, who is active in research in the field of analysis, which has its roots in the development of calculus. For example, the discovery of the structure of DNA in the early 1950s was possible because of previous work on the mathematics of analyzing signals to identify their components.

Sometimes, curiosity-driven mathematics research finds more immediate use. In the 1990s Peter Sarnak, the Eugene Higgins Professor of Mathematics, and two fellow mathematicians, Alexander Lubotzky of the Hebrew University of Jerusalem and Ralph Phillips of Stanford University, introduced Ramanujan graphs, which are arrangements of dots, with pairs of dots joined by edges according to specialized rules of number theory. They showed that for these graphs, the dots were highly interconnected, but with the fewest possible connections. This turned out to be of great interest in computer networking, where engineers could cut costs by using fewer wires between nodes without sacrificing connectivity. Other examples of curiosity-driven investigation leading to practical applications include the research of Professor of Mathematics Assaf Naor on the field of computer science and the research of Charles Fefferman, the Herbert E. Jones, Jr. ’43 University Professor of Mathematics, on the study of fluids.

New findings and insights in mathematics can take years to develop, but the effort pays off, said Gabai, who is on sabbatical at the nearby Institute for Advanced Study, a leading center for theoretical research. “A career in mathematics research is about enduring frustrations with tenacity, being willing to be stuck on a problem, having an open mind and trying things others haven’t,” Gabai said. “The path is not easy, but it is incredibly rewarding in the end.”

Albert Einstein

Einstein’s legacy

Although Albert Einstein was never on the faculty at Princeton, he occupied an office in the University’s mathematics building in the 1930s while waiting for construction of the Institute for Advanced Study, and his ideas have inspired generations of physicists and mathematicians at Princeton and around the world.

The year 2015 marks the 100th anniversary of the most profound of Einstein’s intellectual feats, general relativity, a theory that explains the relationship between gravity and matter. With this work, Einstein unleashed extraordinary new concepts such as black holes, the Big Bang, the bending of light by galaxies, and the rippling of gravitational waves through space, all consequences of the theory and the mathematical equations that describe it.

Einstein’s theory explains how matter, in the form of galaxies, suns, planets and other objects, creates gravitational fields in the fabric of the universe and how these gravitational fields in turn control the behavior of matter. His ideas, set forth in a series of lectures in late 1915, were almost immediately applied to describe, for example, the unconventional orbit of the planet Mercury.

But although the theory is easy to explain in words, the underlying math, in the form of partial differential equations, is considerably more complicated. “Einstein’s equations provide a tremendous number of deep problems for mathematicians,” said Sergiu Klainerman, the Eugene Higgins Professor of Mathematics. “These are some of the most difficult equations there are, by far.”

Klainerman is one of a group of Princeton mathematicians working on general relativity that includes Rodnianski; Mihalis Dafermos, the Thomas D. Jones Professor of Mathematical Physics; Alexandru Ionescu, professor of mathematics; Stefanos Aretakis, assistant professor of mathematics; and several postdoctoral researchers and graduate students.

Finding new ways to understand these equations could aid in the understanding of black holes, regions of extremely dense gravity that were predicted by Einstein’s equations long before they were observed in the universe. One of the outstanding problems in general relativity is to explain mathematically how a process called gravitational collapse results in a black hole. “We want to understand what it is about the present that tells us a black hole will form in the future,” Rodnianski said.

Another area of research is cosmic censorship, first posed by physicist Roger Penrose, which can be roughly translated as, “Whatever happens in a black hole stays in a black hole.” In other words, mathematicians want to find proof that the intense gravity in a black hole cannot come out to wreak havoc in the universe. “It is a very comforting thought,” Klainerman said, “but it is a very difficult mathematical problem, and one of our long-term objectives is to prove it or disprove it.”

Maria Chudnovsky

Maria Chudnovsky. PHOTO BY DENISE APPLEWHITE

Dinner party mathematics

Imagine you are planning a banquet. You want to make sure that if two people don’t like each other, they don’t sit at the same table. To help with planning, you might draw a diagram with dots for guests and lines joining the pairs that are best kept apart.

Maria Chudnovsky studies mathematical objects called graphs, which consist of dots and lines, with each line connecting two dots. “A graph is a good tool to model real-life situations where the information comes in pairs,” Chudnovsky said, “such as pairs of cities connected by a direct flight, pairs of people who know each other, or pairs of computers connected by an optical fiber.”

Assigning the dots on the graph (or people at your banquet) into groups, so that no conflicts occur is, in mathematical parlance, called “coloring” the graph. That means coloring the dots so that no two dots, or nodes, of the same color are connected. (Think color-coding the tables, and then “coloring” the guests according to their assigned table.)

No efficient algorithm exists for coloring that applies to all situations, Chudnovsky said, but there are classes of graphs, such as one called the “perfect graphs,” that behave particularly well with respect to coloring. While a graduate student at Princeton, Chudnovsky was part of a team — made up of Chudnovsky’s Ph.D. adviser and Professor of Mathematics and Applied and Computational Mathematics Paul Seymour, Neil Robertson of Ohio State University, and Robin Thomas of the Georgia Institute of Technology that solved a 40-year-old problem: a conjecture stating that there is always a simple reason why a graph is not perfect. The conjecture they proved is called “The Strong Perfect Graph Theorem.”

“It was very exciting to accomplish this as a graduate student — it was as huge a shock as you can imagine,” Chudnovsky said. She went on to become a professor at Columbia University before returning last year to Princeton, where she is now a professor of mathematics and the Program in Applied and Computational Mathematics. She receives funding for her research from the National Science Foundation and the United States-Israel Binational Science Foundation.

More recently, Chudnovsky has been exploring another question about perfect graphs. Can you efficiently color the dots with the smallest possible number of colors? The answer to this question is yes, but all the known algorithms use a complex technique known as combinatorial optimization. Might there be another technique that relies solely on graph theory? Recently, Chudnovsky and Columbia graduate student Irene Lo, with Frédéric Maffray at the Grenoble Institute of Technology, Nicolas Trotignon of École Normale Supérieure de Lyon, and Kristina Vuškovi of the University of Leeds, were able to make progress on this, designing such an algorithm for a large subclass of perfect graphs.

Manjul Bhargava

Manjul Bhargava. PHOTO BY DENISE APPLEWHITE

Caution: Elliptic curves ahead

Manjul Bhargava was warned long ago never to think about math while driving. “I find doing mathematical research requires very deep concentration,” said Bhargava, the Brandon Fradd, Class of 1983, Professor of Mathematics. “It is almost like a meditative state.”

On a sunny afternoon in his office, however, Bhargava is lively and enthusiastic as he talks about his research. He is known about campus for his mathematical accomplishments (in 2014 he won the Fields Medal, considered the highest honor in mathematics) and for his popular freshman seminar, “The Mathematics of Magic Tricks and Games.”

But it is his research on curves — or more precisely, elliptic curves — that has the mathematical world taking notice. Beautiful and practical, elliptic curves are at the forefront of mathematics research and are increasingly being used to secure the privacy of online transactions, from credit card purchases to iMessages.

They are also worth $1 million in prize money to the person who can explain them. Elliptic curves are at the heart of one of the seven greatest unsolved mathematical puzzles of our time, according to the Clay Mathematics Institute, which offers the prize. A team including Bhargava and Princeton Professor of Mathematics Christopher Skinner, along with mathematician Wei Zhang of Columbia University and Arul Shankar, who earned his Ph.D. at Princeton and is now at Harvard University, is making exciting progress.

Elliptic curves have captivated mathematicians because they have a special property: If you draw a straight line through any two points on the curve, that line will always intersect th this unusual — no other kind of equation has this property — but cryptography schemes can use this property to encode passwords.

“There is no known set of instructions for how to solve these equations, or even whether or not it is possible to solve them,” said Skinner. Skinner and Bhargava receive support for their research from the National Science Foundation and the Simons Foundation.

So far, mathematicians have shown that some elliptic-curve equations have an infinite number of solutions that are “rational,” meaning they are either whole numbers or they are fractions. Other equations have a finite number of rational solutions. The $1 million prize will go to the person or team that confirms that there is a way to tell whether there are an infinite or finite number of rational solutions, thereby proving a mathematical idea known as the Birch and Swinnerton-Dyer conjecture.

Contributions from Bhargava, Skinner, Shankar and Zhang have found that the conjecture is true for 66 percent of elliptic curves. This is still a long way from proving that the conjecture is true for all curves, warned Bhargava. “We need some additional ideas before we can prove that the conjecture is true for all curves.

Advanced course: A sampling of mathematics research areas

Number theory: Strange patterns pervade our counting numbers. Why do prime numbers usually appear in pairs separated by one number (3 and 5, 5 and 7, 11 and 13, and so on)? Finding the hidden behaviors and patterns of numbers is the basis of number theory.

Analysis: Any signal, whether it is coming from a violin or from the stars, consists of multiple parts. For example, the sound from a violin consists of the tone plus the harmonics. Analysis enables the evaluation of signals in terms of their basic constituents.

Topology: We can think of shapes in terms of how many holes they have. (A donut has one hole, a figure 8 has two.) Topology describes shapes in terms of whether they retain their identity when they are stretched and deformed, but not ripped or cut.

The department is also strong in many other areas of mathematical research, including applied mathematics, dynamical systems, discrete mathematics, geometry and mathematical physics.

In memory of John Nash

A legendary fixture of Princeton’s Department of Mathematics, John Nash Jr. was renowned for his breakthrough work in mathematics and game theory as well as for his struggle with mental illness. In May 2015, Nash and his wife, Alicia, died in an automobile accident while returning from Oslo, Norway, where Nash had received the Abel Prize, one of the most prestigious honors in mathematics, from the Norwegian Academy of Science and Letters. “He had a profound originality as if he somehow had insights into developing problems that no one had even thought about,” said department chair David Gabai. “Beyond great originality, he demonstrated tremendous tenacity, courage and fearlessness.”

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Janet Currie investigates the building blocks of children’s success

Janet Currie

Janet Currie PHOTO BY DENISE APPLEWHITE

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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Ashes, images and the survival of democracy

Loutrophoros

A vase known as a loutrophoros that carried water for ritual cleansing and was often placed at the graves of young, unmarried men. Loutrophoros in the manner of Talos the Painter. Berlin, Staatliche Museen. PHOTO CREDIT: JOHANNES LAURENTIUS/ ART RESOURCE, NEW YORK

Ashes, images and the survival of democracy: Nathan Arrington searches for meaning in ancient Athens’ public cemetery

By Catherine Zandonella

IT’S AN OVERCAST AND WINDY DAY, cold for June, but a strawberry stand across the road reminds us that summer has almost arrived in New Jersey. Nathan Arrington, an assistant professor of art and archaeology, sometimes visits the cemetery near campus to think. “Archaeologists tend to be comfortable with death,” he says.

I walk with Arrington past pitted, moss-stained headstones, wondering if any of those buried here died fighting for a fledgling democracy in the Revolutionary War’s Battle of Princeton. Arrington is an expert on another burial ground, thousands of miles away and 2,500 years in the past, in Athens, Greece, where another fledgling democracy — perhaps the world’s first — was fighting for survival.

The cemetery is an appropriate place for a mystery, and Arrington is exploring a mystery that has captivated him since he was an undergraduate at Princeton in the early 2000s. Back then, he became intrigued by how ancient Greek art included portrayals of their defeats as well as their victories. For example, several of the marble carvings on the Parthenon showed Greeks being speared, trampled and otherwise humiliated in battle. In contrast, Arrington says, “The ancient Assyrians would never portray their warriors as anything but victorious.”

Greek portrayal of defeat

As an undergraduate at Princeton, Arrington was intrigued at how the ancient Greeks portrayed their own defeat in works of art, such as this marble sculpture created around 447-438 B.C. of a centaur trampling a Greek warrior situated on an outside wall of ancient Athens’ largest building, the Parthenon. London, British Museum. PHOTO CREDIT: ALBUM/ART RESOURCE, NEW YORK

The portrayals of Greek defeat would eventually lead him to the larger question of how a young democratic society, at first fighting for survival against foreign aggression and later waging war for territorial expansion, convinced its citizens to sacrifice its young men to war. This topic would become the subject of a several-years obsession and eventually a book, Ashes, Images, and Memories: The Presence of the War Dead in Fifth-Century Athens (Oxford University Press, 2015). It’s a mixture of art, archaeology, history and modern neuroscience, tackling questions of how Athens in the fifth century B.C. developed rituals that helped its citizens accept the war dead as a necessary sacrifice to the survival of the state, rituals that influence us even today.

Mapping Athens’ ancient cemetery

When Arrington was an undergraduate, these findings were still far in the future. He wrote his senior thesis, a major work of scholarship required of all Princeton undergraduates, on the portrayal of defeat in classical Greek art, graduated in 2002 and then departed — first to the University of Cambridge, where he earned a master’s degree, and then to a doctoral program at the University of California- Berkeley. During that time, he spent a year as a Fulbright scholar at the American School of Classical Studies at Athens.

One day in 2008, amid the sound of cars honking and the smell of chestnuts roasting in a street vendor’s cart, Arrington followed Leda Costaki, a research archivist at the American School, on a tour of Athens’ ancient city walls. Most of the walls lie in ruins beneath the concrete and asphalt of the modern city. We know the location of the walls due to the work of government archaeologists who hastily catalogue the historical treasures — crumbling walls, roadbeds, even statues — uncovered whenever the urban landscape is peeled back during the construction of a commercial building or apartment house.

This type of archaeology — the examination of artifacts exhumed from beneath existing development — is considered so hard that a lot of people don’t want to do it. Instead of digging in dirt, urban archaeologists delve through stacks of papers or scroll through computerized reports. But as Arrington traipsed in and out of basements where parts of the walls had been preserved, he realized that it might just be possible to use the reports of these urban archaeologists to learn more about Athens’ ancient public cemetery.

Inspired by Costaki’s tour, Arrington undertook the task of mapping Athens’ ancient cemetery, the dēmosion sēma. Scholars already knew a bit about it from funeral orations and gravestones, but until Arrington, no one had conclusively mapped it or catalogued the locations of the large public graves for the war dead.

Arrington’s map revealed more mysteries. For one thing, the cemetery wasn’t exactly where you might expect a public graveyard to be — it was a little off the beaten path and outside the city — and the graves were not placed in neat rows the way they are in modern veterans’ cemeteries such as the Arlington National Cemetery. Instead, the graves were spread out over an area nearly a mile long that also housed a pottery manufacturing area.

“Sources speak of the [cemetery region] as a quiet place of solitude, or an ideal spot for a walk,” Arrington wrote of what the region would have been like in the fifth century B.C. in his doctoral thesis. “The wide road created an appealing, open space, with many paths leading off to the sides. The public graves did not dominate the edges of the road in a strict line but, like family plots, created smaller, inviting precincts. Such layouts of the monuments encouraged the pedestrian not to stroll by or between memorials, but to pause, experience, explore.”

The mapping of the dēmosion sēmaand study of casualty lists earned Arrington his doctorate degree in 2010, acclaim for his scholarship, and a job the same year as Princeton’s newly hired expert on classical Greece — filling the shoes, incidentally, of his senior thesis adviser, William Childs. Childs, professor of art and archaeology, now emeritus, is impressed with the scholar that Arrington has become.

“He is extraordinarily sensitive and very intelligent,” Childs says when I meet him in a windowless room above Princeton’s Marquand Library of Art and Archaeology. The room is crammed with filing cabinets and the walls are lined with faded black-and-white photos of Princeton archaeologists from a time when men on expedition dressed for dinner. “He covers just about everything — I disagree with him on a few points, but it is first-rate work, and he is a first-rate scholar.”

As an assistant professor at Princeton, Arrington began to piece together the story of what the public cemetery, together with the art and texts of the time, tell us about the lives and customs of a young, militant democracy.

The story starts about 508-507 B.C., when the citizens of Athens set up what is considered the first-ever democratic system of government. The city had hardly gained independence when it faced the threat of Persian invaders. Banding together with other Greek city-states, Athens triumphed over the Persians in 480 B.C. and waged many more battles — not only for survival but to gain power and territory. But the cost of these victories, and also some defeats, was high.

“There was an obvious problem with the war dead,” Arrington says. “You had to convince a society that these wars were worth the risk. And if you are a young democratic community, you need to honor the dead, but you cannot elevate the dead above the rest of society.”

The public cemetery was one way that city leaders sought to make the sacrifice more acceptable, Arrington found. Prior to the dēmosion sēma’s construction, the mourning of family members killed in battle was a very personal experience. Families would go to the battlefield to collect the body. Once home they’d wash the body, and invite extended family and friends to honor the deceased. Those who could afford to do so erected statues and monuments to commemorate the dead.

Once the public cemetery was created, however, the building of private monuments ceased, according to the records and artifacts that Arrington studied. Instead, officials cremated the war dead at the battlefield or somewhere else outside the city, then brought the ashes into Athens by the cartload to display in the burial ground. “This would have been a startling and disturbing sight,” Arrington says.

Individual monuments were replaced by tall slabs of marble called stelae inscribed with lists of names of the fallen. The carvings appear to have been done with some haste, probably in time for an annual celebration that would include speeches and funeral games.

“This was a way to honor people equally,” Arrington says. “You were elevated to the same level as your rich neighbor across the street. Death in battle was the great equalizer.”

Death was also the great anonymizer, he says. Only first names were carved on the stelae. “The anonymity of the lists encouraged a view of dead as a collective instead of individuals. These were fundamental changes in the way that people viewed their dead.”

Coopting the war dead for civic purposes

As Arrington learned more about these customs by studying the stelae, the works of art of the period and surviving funeral oration texts, he began to understand how the Greek battle scenes that had so puzzled him as an undergraduate fit into the picture.

These battle scenes were prominently on display on the crown of Athens’ largest building, the Parthenon, which, with its marble sculpture, was the Times Square of the ancient world. There, for all to see, were carvings of an Amazon spearing a Greek soldier, a centaur trampling a Greek and a Greek soldier turning to run or crawl away. These mythical foes, carved between 447 and 438 B.C., represent real-life battles. The Amazons, for example, wore Persian dress.

The location of these scenes on a sacred building — the Parthenon is a temple to the goddess Athena — suggests a deific stamp of approval. The images of flight, loss, defeat and death are a means of catharsis, creating an emotional connection between the viewer and the defeated, Arrington argues. Long after the funeral orations and games were over, the monuments posed the question to the living: What will you do?

Nathan Arrington

“There was an obvious problem with the war dead. You had to convince a society that wars were worth the risk.”
–Nathan Arrington, assistant professor of art and archaeology. PHOTO BY DENISE APPLEWHITE

How did the Greeks respond to coopting of their war dead for civic purposes? With their private traditions supplanted by public rituals, families over time shaped new customs. One such custom was to place in the cemetery offerings of decorative oil-filled bottles called lekythoi.

At the Princeton University Art Museum in the center of campus, I meet J. Michael Padgett, curator of ancient art. At a back entrance, a security guard checks me in, and Padgett takes me to a room lined with shelves of Greek antiquities where Arrington once worked as a student, and where in turn his students come to study lekythoi and other artifacts in the classes he teaches.

Padgett hands me a smooth vase about the size of a soda bottle. If I drop it, I would destroy an object created thousands of years ago. Holding it makes me feel somehow closer to understanding how a grieving mother might revere such an object, which served as a way of connecting the living and the dead. “Vases are a window on the past, although they are a smudged and cracked window,” Padgett says.

On one of the lekythoi described in Arrington’s book, a woman stands facing a tall grave marker, her outstretched hand holding a lekythos, possibly purchased at the nearby pottery works. A warrior looks at her from the other side of the grave.

From his armor, it is clear that he is a ghost; people didn’t go to graves dressed like that. The image carries a reassuring message for the grieving survivor who held this vase in pre-Christian Greece: Your dead son is here in spirit, and he knows that you visit his grave.

Lekythos

Disallowed from building individual monuments for their loved ones who died in battle, Athenians honored their war dead in the public cemetery by placing small vases called lekythoi at the mass graves. On this lekythos, dating from about 460-450 B.C., a woman carrying a basket with grave offerings on her head offers a lekythos to a striding warrior, probably the deceased. Berlin, Staatliche Museen. PHOTO CREDIT: JOHANNES LAURENTIUS/ ART RESOURCE, NEW YORK

Arrington examined this and other lekythoi as snapshots — the selfies of everyday life and loss in ancient Greece — and started to see how the Athenians used the vases in combination with the public cemetery to make sense of their losses. “What you actually see is the variety of responses to the war dead, to the point of almost being subversive. I wouldn’t call it an antiwar movement, but these were reactions against the city’s claims to the dead, to the bodies or to the endless wars.” Eventually the monuments to individuals returned, paid for by the families who could afford them, around 430 B.C.

Padgett takes the lekythos from my hand. He has clear memories of Arrington as an undergraduate. Just after graduation in 2002, Arrington worked as an intern in the art museum, helping Padgett prepare an exhibition. “Of course I remember Nathan,” Padgett says. “He stood out even then as an extremely bright and motivated student. He has great powers of concentration — and he was already multilingual by then. I and others were delighted when he came back.”

During his undergraduate years at Princeton, Arrington met his wife, Celeste, who is now an assistant professor of political science specializing in the Koreas and Japan at George Washington University. A few years later, while they both were working on their doctorates, Arrington found himself living in Japan. When not sifting through piles of photocopied Athenian archaeology documents, he would visit the Yasukuni war shrine. (“I was the strange tourist just sitting there watching people come and go,” he says.) Here, soldiers who gave their lives for Japan are revered as deities. Around that same time, the U.S.-Iraq war was going on, yet U.S. government policy forbade news photography of the coffins arriving home from Iraq and Afghanistan. He began to think about how our ways of remembering the dead — even today — influence our willingness to accept the personal cost of war.

Crossing the centuries

The sprawling cemetery, the anonymity of the grave markers, the funeral orations, the objects of art from the small lekythoi to the massive marble friezes — all were clues that pointed to ways that societies shape how their citizens view death.

And that led to the last piece of the puzzle: Exactly how did these material objects influence the thought processes of Athenians? Arrington found himself turning to modern neuroscience to learn how our environments and past experiences influence what we remember. We don’t remember everything that happens to us, but rather only those things that have some importance or value. And our biases or mindsets can influence what we remember. The public nature of the cemetery with its ashes on display, funeral games and speeches, plus the anonymity of the markers, carried strong messages that the war dead should be perceived and remembered for their contribution to the state rather than as good sons or dedicated husbands.

Few scholars today could have put together such a comprehensive look at how the objects of art and archaeology revealed something about the culture of ancient Athens, says Matthew Sears, a historian who studies classical Greek warfare at the University of New Brunswick in Canada. “Nathan’s work crosses boundaries between disciplines,” says Sears, who first met Arrington when they were students at the American School of Classical Studies at Athens. “The objects of art that Nathan describes in his book are very well known. They’ve been studied for, in some cases, centuries, but they’ve only been studied in isolation from each other. Nathan brings them all together, as parts of the same story, and he brings in advances in memory and cognitive studies, things that have nothing to do with classical scholarship, in a way that sheds light on how Athenians lived,” Sears says.

A truck rumbles past the strawberry stand outside the cemetery in Princeton. Arrington is leaving for Greece in a few days, where he’ll lead students in an excavation of an ancient trading port on the north coast of Greece. The financial uncertainty in Greece is a worry. Celeste will go with him, and they’ll be bringing their young child (with another on the way), to the dig.

Arrington is musing on how modern society has coopted Greek classical art and architecture to make grand statements. For example, near campus on the Princeton Battlefield stands a neoclassical monument consisting of four Greek columns. “We use classical style as a way to elevate things, but to do that is to not understand the full complexity of Greek art,” he says. “I think we adopted some of these practices without understanding where they are coming from.”

The issues of the treatment of the war dead, the state support of war veterans and the place of war in society are issues that we are still grappling with today, says David Pritchard, a senior lecturer in Greek history at the University of Queensland who is familiar with Arrington’s work. “All of these questions are still being asked. Athens is a very rich point of comparison for thinking about pressing issues of democracy, citizenship and military participation.”

He adds: “Ancient Athens was democratic, but it was a state that was constantly at war. It was a state that prioritized military spending over social security spending, and it was a state that picked fights with other states all the time. So I think that Athens stands as a warning to the modern world that we shouldn’t be complacent in thinking that democracy protects us from warmongering or that democracy means that we only fight just wars, and we only fight necessary wars.”

Western-style democracies, in other words, have much in common with the ancient Greeks when it comes to the war dead: What do you do with the bodies? How will you memorialize them? How will you portray them in images? And will you honor the dead as a way to glorify war?

Arrington is not sure we honor our war dead particularly well. “We as a culture tend to ignore death as much as we possibly can,” he said. “It is difficult for society to come to grips with the cost of war because death is not part of our visual culture on a regular basis, the way it was in the ancient world. Yet these ashes, images and the memories they create are needed if we are to have national healing.”

Arrington’s work has been supported by Princeton University’s David A. Gardner ’69 Magic Project and the Stanley J. Seeger Sabbatical Research Grant.

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Discovery_2015_F_3_Arrington_book_cover_9780199369072Arrington explores how a young democracy coped with the sacrifice of so many of their young men to war in his book Ashes, Images, and Memories: The Presence of the War Dead in Fifth-Century Athens (Oxford University Press, 2015). On the cover of the book is a vase known as a loutrophoros that carried water for ritual cleansing and was often placed at the graves of young, unmarried men. The vase, which dates from about 410 B.C., shows a deceased man looking at an equestrian statue of himself. The vase represents a way that families commemorated their dead and hints at a backlash against the practice of burying soldiers’ ashes en masse in Athens’ public cemetery.