The island is Midway, near one of World War II’s most important naval battles and now a quiet backwater where seabirds far outnumber the tiny human population. But Midway’s location near the center of the Pacific Ocean makes the nearby Great Pacific Garbage Patch accessible to the island’s seabirds scouring the ocean surface for food.

The plight of Midway’s birds took center stage Thursday night during a “Trash Talk” in the Geological Lecture Hall, sponsored by the Peabody Museum of Archaeology and Ethnology and co-sponsored by the Harvard Museum of Natural History. Presented by Max Liboiron, regional co-director of the Plastic Pollution Coalition and a graduate student at New York University, the talk was titled “Terrible and Charismatic Waste: A Close Reading of Ocean Plastics.”

Liboiron provided an overview of plastic pollution in the world’s oceans, describing everything from the computer modeling that shows how ocean currents concentrate floating plastics in the middle of the great gyres that stir the seas to the difficulty that scientists have had getting reliable measurements of how much is out there.

The heart of the problem, Liboiron said, is that the oceans are downstream from literally everywhere, so plastic debris ranging from discarded water bottles to stray supermarket bags washes into streams, flows down rivers, and eventually to the sea. There it joins oceanic waste, such as enormous “ghost nets” abandoned by fishermen. And it all floats with the currents.

Because plastic is stable and long-lived, trash made from it that flowed into the ocean decades ago is still there, Liboiron said, swelled by the steadily accumulating streams of the materials. Scientists are concerned about the effects of the accumulating trash, but Liboiron said there remain questions about the quantity and fate of plastics in the ocean.

Max Liboiron visited the Harvard Museum of Natural History and noted that it was in the early 1960s when an elastic band was found inside a puffin in England. The first recorded instance of plastic pollution, according to Liboiron.

While the images of dead birds, abandoned fishing nets, and inlets coated with floating bottles provoke a visceral reaction, Liboiron said scientists have had difficulty getting baseline measures of ocean plastics on which to evaluate changes year to year. Trawls performed in different years regularly turn up plastic, even in remote oceanic stretches, but the amount collected varies widely from year to year. Even the effect of ingested plastic on seabirds is debatable, with one study indicating that the plastic itself doesn’t harm the birds, though a belly full of plastic can leave little room for food, Liboiron said.

While the idea of ocean currents concentrating plastics may conjure up images of large, mid-ocean accumulations of floating garbage, the reality is more akin to a “soup” than an island, Liboiron said. Plastics of various sizes are scattered throughout the water column, and some is even co-opted by marine life as habitat, as illustrated by the image of a reef fish living in floating plastic piping far from the nearest reef.

While the precise extent of the problem remains elusive, there’s every indication that we now live on a “plastic planet,” Liboiron said, and that we need to consider how to manage the problem rather than envision a return to pre-plastic days.

Plastic can float for centuries. It doesn’t biodegrade into component materials, but can be broken down mechanically into tiny bits of plastic. It can act to magnify chemical pollution in the seas, since it attracts some types of pollutants, which are passed on to creatures that ingest it. One estimate is that there’s more plastic floating in the oceans today than plankton, the tiny drifting plants and animals that form the base of the ocean’s food web.

Though consumers may want to help, plastic recycling is hampered by the many different kinds of plastics in use today, Liboiron said. That means the problem is largely one that is industrial, fed by debris from transfer stations and the use of long-lived plastics on food and other items that by their very nature are short-lived and disposable. One solution, Liboiron said, would be to eliminate the use of plastics for disposable products, while retaining them for longer-lived household items. Another solution, already in effect in Germany, would be to make companies responsible for their products throughout the products’ life cycles, from production to disposal.

Crews are mobilizing to clear paths between the victims and two medical centers. Which roads should they open first, in order to quickly reach the largest number of victims? How many of those roads can they actually clear each day with the equipment available?

This was the problem posed to two teams of tech-savvy students participating in the IACS Computational Challenge in January. The competition was part of ComputeFest, a two-week program hosted by the recently created Institute for Applied Computational Science (IACS) within the Harvard School of Engineering and Applied Sciences (SEAS).

“The amount of debris created by regularly occurring disasters is huge,” said Özlem Ergun, visiting associate professor of applied mathematics at SEAS. In her usual post, Ergun is co-director of the Center for Health and Humanitarian Logistics at Georgia Institute of Technology, where she helps emergency management officials plan their response to disasters.

“The first problem,” she said, “is really to figure out in what order to open the streets so that you create connectivity between the population and the critical infrastructure.”

“The amount of debris created by regularly occurring disasters is huge,” said Özlem Ergun, visiting associate professor of applied mathematics at SEAS. Photo by Eliza Grinnell/SEAS

The Cambridge debris data was generated by Georgia Tech graduate students using the Federal Emergency Management Agency (FEMA) Hazus software, which visually models the human and environmental impacts of earthquakes, hurricanes, and floods.

In the Computational Challenge scenario, 2,478 disaster victims were distributed unevenly across 443 Cambridge locations served by two hospitals (one large, one small), connected by 604 road segments (blocked by varying amounts of debris), and accessed via a fleet of bulldozers that roughly doubled in size over a nine-day cleanup period. A penalty was imposed to simulate the real-life pressure of time — the chance of people losing their lives if help took too long to arrive.

In short, the number of data points and constraints was huge.

The two teams were asked to write code that would find a decent solution within three hours’ time on the high-performance computing cluster at SEAS.

“It’s very tricky in that there are these simultaneous competing goals,” said Chris Beaumont, a visiting student in astronomy at Harvard’s Graduate School of Arts and Sciences. “If it was just, ‘Here’s a map of a city and you have to establish the most efficient path to clear the debris to connect everybody,’ that would be pretty easy — that’s a well-known problem. Or if it was just, ‘Clear things as fast as possible,’ that might be easy. But it’s a combination of different factors, which means you may not take the most efficient path. You might dig some kind of awkward path to get to a really important area as quickly as possible.”

For a problem this complex, the teams had to translate every parameter and constraint into the vocabulary of network theory. Hospitals became “source nodes”; population points became “demand nodes.” Roads became “edges,” each with a weight corresponding to the resources required to clear it. Through the lens of computational science, the storm-ravaged city became a vast data set and a question of multi-period network expansion.

“Most of our creativity went into formulating the problem,” reflected Ariana Minot, a first-year graduate student in applied mathematics. “I’ve never tried to solve a problem that wasn’t in the context of the course I’d taken, where there were assumptions about what kind of methods to use, so that was really different.”

Minot and her teammates, Yu Qin and Yifan Wu ’14, knew early on that they would need to devise an algorithm that could see the “big picture.” A poor algorithm might start opening roads in a westward direction to reach a nearby pocket of 20 people, blind to the fact that a group of 100 people were only slightly further away, to the east.

Their final algorithm drew on a concept from biology, imitating the strategy of foraging ants. As the insects explore the environment around the nest, they leave a trail of pheromones that gradually evaporates. The ants follow their neighbors’ familiar scent, so the shortest, most efficient paths become more frequently traveled. As a result, despite the randomness of the ants’ initial explorations, the colony as a whole is able to quickly select the optimal route to the food.

Beaumont and his teammate Blessing Okeke, a teaching fellow in applied mathematics, chose a different approach. They wrote an algorithm that finds a viable (though inefficient) solution quickly and then “perturbs” it with random changes to try to improve it in the remaining time.

“I think we got a good high-level idea of what the problem was pretty quickly,” said Beaumont. “The main problem is that there are so many potential solutions you can try, so you have to be intelligent about the different options you explore.”

They found success with simulated annealing, a technique inspired by metallurgy, in which a metal is repeatedly heated and cooled so that the particles can settle into place and harden. In an algorithmic sense, it’s a way to repeatedly identify slight improvements to a solution.

“It’s a really interesting application of physics, computationally, to a real system,” said Rosalind Reid, executive director of IACS.

The teams, coached by lecturers Mauricio Santillana and Pavlos Protopapas, presented their approaches for feedback from Ergun and members of the IACS advisory board partway through the challenge.

“When you characterized the problem, I think you characterized it correctly as saving lives rather than finding the very best solution,” IACS board member and Oracle software architect Guy Steele ’75 told the first team. “If you’re in a search space where just finding a ‘good enough’ solution is adequate, you can probably find much faster algorithms.”

To win the challenge, he added, “you don’t necessarily have to find the very best answer.”

With a hypothetical population of 2,478 victims, and penalties accruing at the end of each period, the final scores were expected to be somewhere between 5,122 (the estimated best possible solution given unlimited computing power) and approximately 10,000 (clearing roads at random).

Beaumont and Okeke won the challenge by saving the most people in the shortest time, achieving a final score of 6,793.

It was clear, however, that the winners’ excitement had less to do with the iPad prizes and more to do with the challenge experience — just what Protopapas had expected when he conceived of organizing a student challenge during the winter break.

“It gives them an opportunity to get down to doing a hard problem,” said Ergun. “I imagine that’s an empowering thing to do.”

To read more about the IACS Computational Challenge and the winning approach, visit Chris Beaumont’s blog.

It’s also one that’s almost completely misplaced, said George Lauder, the Henry Bryant Bigelow Professor of Ichthyology.

Experiments conducted in Lauder’s lab and described in the Feb. 9 issue of the Journal of Experimental Biology reveal that, while sharks’ sandpaperlike skin does allow the animals to swim faster and more efficiently, the surface of swimsuits such as the Speedo Fastskin II has no effect when it comes to reducing drag as swimmers move through the water.

“In fact, it’s nothing like shark skin at all,” Lauder said of such swimsuit material. “What we have shown conclusively is that the surface properties themselves, which the manufacturer has in the past claimed to be biomimetic, don’t do anything for propulsion.”

That’s not to say that the suits as a whole do nothing to improve performance.

“There are all sorts of effects at work that aren’t due to the surface,” Lauder said. “Swimmers who wear these suits are squeezed into them extremely tightly, so they are very streamlined. They’re so tight they could actually change your circulation and increase the venous return to the body, and they are tailored to make it easier to maintain proper posture even when tired. I’m convinced they work, but it’s not because of the surface.”

By comparison, Lauder said, the research showed that the millions of denticles — tiny, toothlike structures — that make up shark skin have a dramatic effect on how the animals swim by both reducing drag and increasing thrust.

“What we found is that as the shark skin membrane moves, there is a separation of flow. The denticles create a low-pressure zone, called a leading-edge vortex, as the water moves over the skin,” he said. “You can imagine this low-pressure area as sucking you forward. The denticles enhance this leading-edge vortex. So my hypothesis is that these structures that make up shark skin reduce drag, but I also believe them to be thrust-enhancing.”

Importantly, however, the phenomenon was only found when the skin was attached to a flexible membrane. When placed on a rigid structure, no increases in swimming speed were seen.

“In life, sharks are very flexible. Even hammerheads and large ocean sharks are quite flexible,” Lauder said. “If you watch a shark swim, the head does not move very much, so it could be that the denticles on the head are mostly reducing drag, but those on the tail are enhancing thrust. But we don’t know what that balance may be. Ultimately, though, one of the key messages of this paper is that shark skin needs to be studied when they’re moving, which hadn’t been done before.”

Studying how shark’s skin helps them move through the water, however, is no easy proposition, and one that, for obvious reasons, can’t be done using live animals.

To perform the tests, Lauder and his team obtained samples of the skin of mako and porbeagle sharks and tested them alongside two other materials, the high-tech swimsuits and a material that featured tiny grooves, or “riblets,” which has been explored as a way to cut fuel consumption on aircraft and reduce drag on sailboats.

To conduct the tests, each of the materials was mounted on two forms, one a rigid, winglike structure and the other a flexible membrane. Each was then attached to a robotic arm mounted on a low-friction device suspended over a recirculating tank. To measure the speed at which the apparatus “swims,” researchers turned up the flow in the tank until the device returned to its starting point.

Understanding how water flowed over each material, however, was trickier.

To get at the problem, Lauder and his team relied on a technique called particle image velocimetry, which uses a laser to illuminate millions of reflective particles in the water. Using a high-speed camera that records at up to 1,000 frames per second, researchers can observe how the particles move and see where and when vortices form.

“I’ve thought for years that the literature on shark skin needed an upgrade,” Lauder said, explaining his motivation for the research. “Once we got going, I thought it would be fun to look at the Speedo materials, because we don’t have a lot of quantitative information on the effect of surface structure.

“Going forward, we want to try to image the flow as close to the surface as we can reasonably get,” he continued. “The other direction we are exploring is to make an artificial shark skin and then manipulate it — delete every other denticle, make them twice as large, or change the spacing — and see what effects that may have.”

Funding for the research was provided by the National Science Foundation.

The roots of hunger, eating, and weight are based in the brain’s complex and rapid-fire neurocircuitry. Over the years, nerve cells containing agouti-related peptide (AgRP) protein and pro-opiomelanocortin (POMC) protein have emerged as critical players in feeding behaviors. Located in the hypothalamus, the brain area that controls automatic body functions, AgRP neurons have been shown to drive eating and weight gain while POMC neurons inhibit feeding behaviors, causing satiety and weight loss.

Described in the Feb. 9 issue of the journal Neuron, the findings show that during fasting, the AgRP neurons that drive feeding behaviors actually undergo anatomical changes that cause them to become more active, which results in their “learning” to be more responsive to hunger-promoting neural stimuli.

“The role of plasticity has generally not been evaluated in neuronal circuits that control feeding behavior, and with this new discovery we can start to unravel the basic mechanisms underpinning hunger and gain a greater understanding of the factors that influence weight gain and obesity,” explains senior author Bradford Lowell, an investigator in BIDMC’s Division of Endocrinology, Diabetes and Metabolism and professor of medicine at Harvard Medical School (HMS).

Adds BIDMC Chairman of Neurology Clifford Saper, “For most animals, finding enough food to survive is their biggest daily challenge, and so the brain’s increase in feeding drive may be adaptive. But, for humans who are overweight, reducing this drive to the AgRP neurons may prove to be a path to future weight loss therapies.”

Previous work by the Lowell lab and others had demonstrated that when AgRP neurons in mice are artificially switched on, the animals eat voraciously, consuming four times more than control animals. “The ‘switched-on’ animals search in an unrelenting fashion for food, and when given a task to obtain pellets, will work five times harder to get them,” Lowell explains. “Given the important role played by AgRP neurons, we had a great interest in understanding the factors that regulate their activity.”  While much focus had centered on hormones, including leptin, insulin, and ghrelin, the Lowell team hypothesized that other nerve cells might be the mechanisms that were regulating neuronal activity.

Neurons communicate with one another via neurotransmitters, chemical messengers that traverse synapses, the specialized junctions between upstream and downstream neurons. Glutamate is one such excitatory neurotransmitter.

“Studies in other regions of the brain [for example, those controlling learning and reward and addiction behaviors] have demonstrated that glutamate synapses are highly plastic, changing in their strength and sometimes even in their number,” explains Lowell. Shown to exert powerful control over behavior, synaptic plasticity is brought about when glutamate binds to NMDA receptors on downstream neurons.

“When glutamate gets released by upstream neurons and binds to NMDA receptors, calcium enters the downstream neuron. This, in turn, engages signal transduction pathways that cause synaptic plasticity. In other parts of the brain, such as the hippocampus, NMDA receptors drive plasticity which serves to encode memories,” Lowell adds.

Led by co-first authors — Tiemin Liu, Dong Kong, Bhavik P. Shah, and Chian Ping Ye — the investigators created and studied mice genetically engineered to lack glutamate-binding NMDA receptors on the AgRP neurons. For the sake of comparison, they also created mice genetically engineered to lack NMDA receptors on POMC neurons.

They found that while mice lacking NMDA receptors on POMC neurons showed no change in feeding behavior, the situation was dramatically different in the mice lacking NMDA receptors on AgRP neurons.  “These mice ate a lot less and were much skinnier than a group of control mice,” explains Lowell. Furthermore, the scientists found that a 24-hour period of fasting — which causes intense hunger in the control mice — was associated with a 67 percent increase in the number of dendritic spines on the AgRP neurons.

“Dendritic spines are tiny structures attached to the neuron’s dendrites, the treelike branches that receive incoming signals from upstream neurons,” explains Lowell. “These structures are the physical site, the subcellular communication hub, where synaptic input from upstream glutamate-releasing neurons is received, typically one synaptic input per spine.”

“I’ve been studying spines for a long time and I’ve never before seen a manipulation that triggered such rapid and robust changes in spine number,” says co-author Bernardo Sabatini, a Howard Hughes Medical Institute investigator in the Department of Neurobiology at Harvard Medical School (HMS). “Clearly, feeding is plugging in to the most basic mechanisms that control synapse and spine number in these cells. This may be a great system to understand not only feeding behavior, but also to understand the cell biology behind dynamic synapse formation and retraction.”

When the control mice were re-fed — and their hunger alleviated — the number of spines dropped back to normal. (In contrast, fasting had no effect on spine number in the mutant mice lacking NMDA receptors on AgRP neurons.) These dramatic changes in spine number and their tight association with states of hunger and satiety in control mice — and the absence of changes in spine number in mice lacking NMDA receptors on the downstream AgRP neurons — strongly suggests that structural plasticity of excitatory glutamate synapses on AgRP neurons is an important regulator of feeding behavior, says Lowell.

“Obesity is a major risk factor for type 2 diabetes, cardiovascular disease, and certain types of cancer,” he adds. “By understanding the neurobiological mechanisms underlying feeding behaviors, we can work on treatments for a problem that has now become a global epidemic. These findings move us closer to a mechanistic understanding of how various factors controlling hunger might work.”

This study was supported by grants from the National Institutes of Health and the American Diabetes Association, as well as support from the Shapiro Predoctoral Fellowship and the Parkinson’s Disease Foundation postdoctoral fellowship programs.

In addition to Lowell, Sabatini, and the paper’s first authors, other co-authors include BIDMC investigators Shuichi Koda and Zongfang Yang and HMS investigators Arpiar Saunders and Jun B. Ding.

As described in a recent paper in the journal Nature Methods, the research is aimed at answering one of the most fundamental, long-standing questions about how the brain gives rise to behaviors.

“What we have shown is that the larvae really make left- and right-steering decisions based on sensory input,” said Aravinthan Samuel, professor of physics and co-author of the paper. “We now believe we have a complete algorithmic picture of how those decisions are made, based on the ways in which motor activity is regulated by these inputs. We know smells cause the animal to initiate a navigational decision. And once that navigational decision starts, we know how it’s carried out.”

At the heart of the work was an unusual piece of technology, the Linear and Dynamic Gaseous Gradient Apparatus — or LADY GAGA for short — that allowed researchers to precisely control odors in the air.

“This was the most challenging stimulus-control system we’ve ever built,” Samuel said of the device. “It works by pushing air across a plate to create a very slight breeze — approximately one centimeter per second — while a series of switches injects scents into the airflow.”

Using a computer program to control precisely when, where, and how much scent is injected enables the device to produce a perfectly linear gradient of odor across the plate. At one end, Samuel said, the scent is absent, while it is unavoidable at the other. Unlike similar experiments, which typically used a droplet of an odor-producing chemical, the breeze prevents the odor from diffusing throughout the device. As long as it is renewed by the injector, the scent effectively stays put.

“The problem with earlier experiments is that when you put a scent on one side of the plate, you can’t keep it there,” said Marc Gershow, a postdoctoral fellow in physics and designer of the device. “Over time, it will diffuse.”

In addition to LADY GAGA, Samuel and his team relied on another oddly named piece of technology to unlock navigational behavior, the MAGAT analyzer.

Short for Multiple Animal Gait and Trajectory Analyzer, the technology is a software package that uses a high-resolution camera to track dozens of larvae as they move in reaction to stimuli. Once placed on the plate inside LADY GAGA, the analyzer showed that larvae sweep their heads to the left and right to sample the environment, then made a decision on which way to move based on the input they receive.

Using that data, Samuel said, the next step is to understand “how that algorithm is written in the wiring diagram of the brain.”

Doing so will require another device with a celebrity namesake, CoLBeRT — short for Controlling Locomotion and Behavior in Real Time — a tracking microscope that allows researchers to track individual larva and stimulate specific neurons using pulses of laser light.

“The nice thing about the larva is that it’s optically transparent,” Samuel said. “It also has a small brain, with less than 10,000 neurons, so we should be able to map all the processing of odor information to the increased or decreased activity of a specific circuit in the brain.

“Once we figure out what that circuit is, we can determine how the patterns of activity in that circuit correlate with observable behavior. Using CoLBeRT, we may also be able to ‘push’ the activation into a neuron, even in the absence of a sensory input, and get the animal to behave as if the input was actually there.”

The larvae may seem relatively simple creatures, but Samuel believes that studying them will ultimately uncover the general principles for how the nervous systems of higher animals work.

“If there are general principles for understanding how an entire nervous system orchestrates itself to do purposeful things, those principles will be ferreted out with simple organisms,” he said. “And if that’s true, maybe we don’t give these little organisms enough credit.”

The researchers found that such belated conversations tend to occur under particularly stressful conditions — when patients have been admitted to a hospital for acute care. And the doctor who shares in the end-of-life care talk is often a hospital physician rather than an oncologist who has treated the patient for much of his or her illness.

Together, these circumstances may deprive patients of the opportunity for extended reflection and deliberation that would have been possible months earlier, when the conversation also could have occurred under less trying and hectic conditions, the authors suggest.

“Previous studies have shown that patients who discuss their end-of-life care preferences with a physician are more likely to choose palliative, comfort-focused care over aggressive measures, and [to] receive hospice or other care consistent with their wishes. But studies haven’t looked at the timing of these discussions, or where and with whom they occur,” says the study’s lead author, Jennifer Mack of Dana-Farber/Children’s Hospital Cancer Center. Mack is also an assistant professor of pediatrics at Harvard Medical School (HMS).

The new study, which involved 2,155 patients with stage IV (highly advanced) lung or colorectal cancer, found that 73 percent of the patients had a conversation about end-of-life care with a physician, according to medical records or an interview with the patient or a companion. Among the nearly 1,000 patients who passed away and whose records document an end-of-life care discussion with a physician, the median time of those discussions was 33 days before death.

Other findings pertain to the location of those discussions and the type of physician involved. Of the more than 1,000 end-of-life care discussions in medical records, 55 percent occurred in the hospital. Oncologists documented end-of-life care talks with only 27 percent of their terminally ill patients in the study.

Data for the study was provided by the Cancer Outcomes Research and Surveillance Consortium (CanCORS), a multi-region, population- and health system-based study of more than 10,000 patients with lung or colorectal cancer. Researchers interviewed patients at two time points and analyzed their medical records 15 months after diagnosis.

“It’s encouraging to see such a high percentage of patients had end-of-life care conversations with a physician,” Mack says. “There’s a concern, though, that so many of these talks are taking place late in the trajectory of the disease.”

Previous studies had estimated that fewer than 40 percent of patients with advanced cancer had end-of-life care discussions. Mack theorizes that this lower figure may reflect that earlier studies didn’t record end-of-life talks that took place shortly before patients’ death.

Other research has suggested that physicians may delay end-of-life care discussions because of a natural reluctance to broach the subject, or because it conflicts with physicians’ problem-solving, hope-giving image. While such motivations are understandable, Mack says, they may work to patients’ detriment if they postpone the conversations too long.

Mack and her colleagues are planning future studies to examine the quality and content of end-of-life care conversations, and then explore whether having such talks earlier in the course of illness can benefit patients.

The study’s senior author is HMS Professor of Medicine Jane Weeks of Dana-Farber. Co-authors include Angel Cronin and Nathan Taback of Dana-Farber; Haiden Huskamp and Nancy Keating of Harvard Medical School; Jennifer Malin of the University of California, Los Angeles; and Craig Earle of the Ontario Institute for Cancer Research.

The study was funded by grants from the National Cancer Institute, the U.S. Department of Veterans Affairs, the American Cancer Society, and the National Palliative Care Research Center.

Creating new materials from abundant, natural plant sources, today’s biomedical and biochemical engineers are finding clinical uses for new “custom” materials that were not even remotely considered in recent decades.

Both renewable and remarkable, plant-based medical products are on the cutting edge of a field called “sustainable biomaterials,” a topic so intriguing that 23 undergraduates chose to spend an extra week at the Harvard School of Engineering and Applied Sciences (SEAS) to take a course on it during their winter break.

“It was engaging, comprehensive, and demonstrated just how ‘sexy’ science can be,” said Aubrey Walker ’15.

The seminar-style mini-course was led by Sujata Bhatia, assistant director for Undergraduate Studies in Biomedical Engineering, who arrived at SEAS last spring. As an industry scientist at DuPont, Bhatia had been at the forefront of research resulting in clinically relevant products, including plant-based tissue adhesives. She now brings that expertise to guide an agile and modern curriculum at SEAS.

Bhatia, who received a grant from the Harvard President’s January Innovation Fund for Faculty to offer the course, intended it as a “vehicle to really get undergraduates thinking about their paths in engineering, and to give a broader overview than they might get in any single course during the semester.”

“I hope that this will both draw undergraduates into the concentration and give concentrators the tools necessary to begin asking their own questions within the field,” she said.

For Walker, a freshman, the course was an inspiring introduction to the breadth of opportunities available in engineering.

“Through the lens of a bioengineer, I felt myself at the precipice of innovative solutions to some of our generation’s biggest problems,” he said. “I can’t imagine a more concise, intellectually stimulating, or rewarding program. I am very glad to have come back from my long break to gain this experience.”

During the week, the students attended foundational lectures on biomaterials and new methods of drug delivery. They also had the opportunity to survey some of the current research in the field by attending the Bio-Inspired Engineering International Symposium, which was hosted by Harvard’s Center for Nanoscale Systems on Jan. 17.

Brandon Geller and Robyn Tsukayama of the Harvard Office for Sustainability gave a guest lecture on biopolymers, providing students insight into the strides that the University is making to integrate the fruits of bioengineering research into its operations.

In addition to seeing the work of experts in the field, students were able to learn about research that their classmates are undertaking. Seniors in engineering, including Erfan Soliman ’12, led one of the week’s sessions by discussing their thesis research and introducing the groups to the laboratory and design spaces that are available to students at SEAS.

Soliman’s work, which combines agar gel and corn-derived carbon nanotubes into a substrate for neural regeneration, extends far beyond the traditional boundaries of his own concentration, electrical engineering.

In addition to presenting a poster at the Bio-Inspired Engineering Symposium, Soliman was able to connect with other students, across disciplines. He teamed up in the lab with Godwin Abiola ’14, a biomedical engineering student, in January, teaching him about circuit theory in order to measure the electrical conductivity of the agar gels.

The partnership between Soliman and Abiola is typical of a trend of collaboration at SEAS that Bhatia believes is here to stay.

“It’s very powerful, and it helps students appreciate early on the importance of bringing diverse perspectives to a project,” she said. “I’ve always been interested in the interfaces between different disciplines. That’s where all the cool things can happen.”

Those pondering the earliest stirrings of life expect that it will either turn out to be easy to create and a natural outgrowth of the primordial conditions found on planets like Earth: rocky, not too hot, not too cold, with water and other key elements. If that’s the case, the rapid acceleration of discoveries of extrasolar planets would mean there are potentially millions of other worlds that are Earth-like enough for life to arise.

Or, life may be hard to get going, requiring a precise combination of conditions and chemicals that were present on Earth, perhaps fleetingly and only once. If that’s the case, such conditions may be difficult to locate in other places, and we may find ourselves in thin company — or even entirely alone — in the universe.

So far, researchers have run into one knotty problem after another. But Nobel laureate Jack Szostak, a genetics professor at Harvard Medical School, and distinguished investigator at Harvard-affiliated Massachusetts General Hospital, said Feb. 1 that we shouldn’t interpret the difficulty of the problems so far to mean that life is most likely rare in the universe.

“At this stage in our thinking, there are a lot of gaps in our understanding, places where we have no idea what happened,” Szostak said. But “problems that looked so intractable in retrospect look simple.”

Szostak, who won the 2009 Nobel Prize in physiology or medicine, spoke at the Harvard Museum of Natural History in the kickoff lecture of the season’s “Evolution Matters” series. Szostak gave a packed Geological Lecture Hall an overview of the work of researchers like himself who are seeking to answer life’s most fundamental question: Where did we come from?

Szostak’s research focuses on understanding primitive cells, how they might have been created, and how they might have behaved and divided. Among other findings, Szostak and colleagues have shown that cell-like vesicles are relatively easy to create from fatty acid molecules suspended in water. He has also shown that vesicles divide naturally when passed through a smaller pore, and explored other possible methods of early cell division.

One of the early problems researchers in this field faced was how genetic information in the first cells was transmitted. The way cells work today, Szostak said, is that the information in DNA is taken by RNA and used to create a vast array of proteins, which do much of the body’s work. This DNA-to-RNA-to-protein process feeds back on itself, with proteins playing key roles in creating RNA from DNA. Scientists found such a closed loop difficult to unravel: With no proteins in an early cell, how do you get the DNA’s information out to create RNA and then more proteins?

That changed in the early 1980s, when researchers discovered that RNA, in addition to having the ability to carry genetic information, also can catalyze chemical reactions, something thought to be the domain of proteins. The discovery gave rise to the possibility that early cells held their genetic information not in DNA, but in RNA molecules, as some viruses do today, and that RNA, not proteins, could have played a role in catalyzing the cellular processes. The problem changed from needing three kinds of molecules that interacted in complex ways to needing just one kind.

While that presented a plausible scenario, many details remain problematic. Two of them, it turns out, are solved with a single solution, Szostak said. One issue is that when two RNA molecules are joined to form a double helix, pulling them apart to get at their genetic information is very difficult without using cellular enzymes, which wouldn’t have been present in early cells.

The second problem is that the molecular backbone occurring in RNA that is created through chemical processes like those possible on early Earth is not the same as that manufactured inside cells. When cells make RNA, the molecular backbone bonds with different atoms at specific locations. When RNA is made through primitive chemical processes, there is more sloppiness, with atoms attached in the wrong spot in some cases.

Both seemed intractable problems, Szostak said. But when members of his lab replicated the situation, evolving an RNA molecule through chemical processes, they realized that instead of being a problem, the sloppiness in the backbone was actually a solution. A few misplaced atoms didn’t affect the whole RNA molecule’s structure, and with those atoms out of place, it didn’t bond quite as strongly to another RNA molecule, allowing them to come apart more easily and letting replication proceed, solving the first problem as well.

“Instead of being a fatal problem for RNA, we now think that backbone heterogeneity may be what allowed RNA to emerge as primordial genetic material,” Szostak said. “Our thinking on this problem is just completely inverted.”

But to Samuel, working on anesthetized or immobilized worms can only tell you so much about how the brain and nervous system work. To truly understand the system, researchers need to see it in action.

So Samuel and researchers in his lab set to work designing equipment that could measure nerve activity in living, wiggling worms. They first succeeded three or four years ago, becoming the first to record neural activity in freely moving worms. Then, last year, they topped that, using pulses of green and blue light on worms that had been genetically modified so that their nerves contained light-activated proteins. This allowed researchers to exert control over the worms by aiming pulses of light at specific nerves.

To do this, they had to design some sophisticated equipment: a tracking microscope to follow the worms’ movements and image-processing software to estimate the location of individual neurons and control a mirror to direct light to the target nerve cells.

The system worked spectacularly. Researchers were able to simulate a touch that caused the worms to recoil by shining a light at a nerve near the worms’ front. They were able to goose the worms into action by shining a light at a nerve toward their back end. They were able to steer a worm left and right and even get it to lay an egg, all without a single physical touch.

At the time, Samuel described the method as perhaps his lab’s “greatest invention” and said it would provide a new tool in the arsenal of researchers seeking to understand the nervous system.

Today, Samuel and members of his lab are moving ahead with their work on the roundworm. Samuel, a physics professor who uses the tools of that field to explore important biological questions, said he chose to work on C. elegans, a millimeter-long roundworm often used in laboratory research, for several reasons. It is transparent, so researchers can see what’s going on inside it, and it’s so simple that researchers have all of its 302 neurons mapped out. That means researchers seeking a beachhead from which to explore the complex workings of the nervous system can look for basic principles in C. elegans that would also apply to more complex creatures.

After years working on C. elegans, Samuel’s laboratory is tackling increasing complexity. A few years ago, the researchers began working on larva of the fruit fly Drosophila. While Drosophila is another commonly studied laboratory animal — favored for genetics research because of its short life span — it is usually studied in its adult fly form. Its wormlike larva, which Samuel said has a nervous system an order of magnitude more complex than C. elegans, is not as widely studied. One project, if successful, will yield a complete map of the nerves involved in the larvae’s sensitivity to light and heat.

Although he has been on Harvard’s faculty since 2003, Samuel has been at the University far longer, for 23 years. After growing up in Sidney, New York with an interest in mathematics and physics, Samuel came to Harvard as an undergraduate. While looking for laboratories where he could conduct biological or physics research, he visited the lab of Howard Berg, a biophysicist who studies movement in bacteria. Samuel found a home there, conducting both undergraduate and graduate studies under Berg.

“Everything he touched seemed to work. He roamed and read widely. At one point he was learning Japanese … and reading James Joyce,” Berg said. “We are lucky to have him here.  He is working at the interface of physics and biology and needs the support of both communities.”

Samuel said he was attracted to Berg’s lab — and biophysics generally — because so many fundamental biological questions remain unanswered that he felt there were ample opportunities to conduct basic research.

“You can do fundamental work quickly. That’s not so easy to do in physics,” Samuel said.

Samuel received his doctorate in biophysics in 1999, spent four years doing postdoctoral research at Harvard, and then became an assistant professor of physics in 2003. He became an associate professor in 2007 and professor of physics in 2010.

Over his career, Samuel has come to understand what he calls the “inefficiencies” in science, the research down blind alleys that can consume a lot of effort but yield no results. As the leader of his own lab, Samuel said he tries to touch base with each lab member daily instead of waiting for lab meetings, to head off forays down paths that won’t prove fruitful.

“I try to make sure everyone is working on solvable problems,” Samuel said.

The material, made from discarded shrimp shells and proteins derived from silk, is called “shrilk.” It is thin, clear, flexible, and strong as aluminum at half the weight, according to postdoctoral fellow Javier Fernandez, who began work on chitin-based material as a doctoral student at the University of Barcelona and developed shrilk during a year-and-a-half stint working at the Wyss Institute with Director Donald Ingber.

Ingber, the Judah Folkman Professor of Vascular Biology at Harvard Medical School and Harvard-affiliated Children’s Hospital and professor of bioengineering at the Harvard School of Engineering and Applied Sciences, said companies have already expressed interest in the material, particularly for medical applications. Possible medical uses are boosted by the fact that the ingredients in shrilk have already been approved by the Food and Drug Administration. Potential uses include sutures that would dissolve over time in hernia repair, protective coverings for burns and wounds, and a scaffold on which cells can grow to regenerate tissue.

A major benefit of the material, which was described in a December issue of the journal Advanced Materials, is its biodegradability, Ingber and Fernandez said. Plastic’s toughness and moldability represented a revolution in materials science during the 1950s and ’60s. Decades later, however, plastic’s very durability is raising questions about how appropriate it is for one-time applications such as plastic bags, or short life-span consumer goods, used in the home for a few years and then tossed into a landfill where they will decompose for centuries.

“All this plastic, what’s the point of making something that lasts 1,000 years?” Fernandez asked.

Shrilk not only will degrade in a landfill, but its basic components are used as fertilizer, and so will enrich the soil.

Natural materials, Fernandez said, were supplanted by synthetic materials partly because synthetics can be easily controlled in manufacturing and made into a wide variety of goods. Natural materials are making a comeback, however, as scientists learn from nature the manufacturing techniques needed to mimic the properties that make them desirable. Shrilk is a good example of the Wyss Institute’s mission, which is to learn how to make things from nature’s own engineering.

“This is the second chance for natural materials,” Fernandez said.

Shrilk’s secret, Fernandez and Ingber said, is not just its chemistry but also its design. There are two basic ingredients, a variation on the material chitin that makes up a large part of an insect’s tough outer layer, called chitosan, and fibroin, a protein derived from silk. But just combining those two ingredients doesn’t produce a hard, flexible material. Instead of blindly combining the materials, Fernandez and Ingber looked to nature to see not just what materials were used, but how.

In an insect’s body, the fibroin protein and chitin are layered, creating the kind of stiff design that gives plywood its strength and rigidity. By mimicking nature’s design and layering the chitosan and fibroin protein, shrilk was born.

“Much of the structural properties found in nature are not just chemistry, they’re architecture,” Ingber said.

Shrilk has great potential, the two said. Chitin is one of the most abundant materials in nature, found in everything from shrimp shells to insect bodies, snail and clam shells. That makes shrilk not only low cost, but also potentially scalable should it be used in applications demanding a lot of material.

Work on shrilk is continuing in the lab, the two said. Ingber said the material becomes flexible when wet, so they’re exploring ways to use it in moist environments. They’re also developing simpler manufacturing processes, which could be used for products in non-medical applications, like for computer cases and other products inside the home. They’re even exploring combining it with other materials, like carbon fibers, to give it new properties.

In a paper published in the journal Molecular Psychiatry, a team including Harvard-affiliated Massachusetts General Hospital (MGH) researchers reports that a test analyzing levels of nine biomarkers accurately distinguished patients diagnosed with depression from control participants without significant false-positive results.

“Traditionally, diagnosis of major depression and other mental disorders has been made based on patients’ reported symptoms, but the accuracy of that process varies a great deal, often depending on the experience and resources of the clinician conducting the assessment,” says George Papakostas of the MGH Department of Psychiatry and an associate professor of psychiatry at Harvard Medical School, lead and corresponding author of the report.  “Adding an objective biological test could improve diagnostic accuracy and may also help us track individual patients’ response to treatment.”

The study authors note that previous efforts to develop tests based on a single blood or urinary biomarker did not produce results of sufficient sensitivity, the ability to detect the tested-for condition, or specificity, the ability to rule out that condition.  “The biology of depression suggests that a highly complex series of interactions exists between the brain and biomarkers in the peripheral circulation,” says study co-author John Bilello, chief scientific officer of Ridge Diagnostics, which sponsored the current study. ”Given the complexity and variability of these types of disorders and the associated biomarkers in an individual, it is easy to understand why approaches measuring a single factor would not have sufficient clinical utility.”

The test developed by Ridge Diagnostics measures levels of nine biomarkers associated with factors such as inflammation, the development and maintenance of neurons, and the interaction between brain structures involved with stress response and other key functions. Those measurements are combined using a specific formula to produce a figure called the MDDScore — a number from 1 to 100 indicating the percentage likelihood that the individual has major depression.  In clinical use the MDDScore would range from 1 to 10.

The initial pilot phase of the study enrolled 36 adults who had been diagnosed with major depression at the MGH, Vanderbilt University, or Cambridge Health Alliance in Cambridge, Mass., along with 43 control participants from St. Elizabeth’s Hospital in Brighton, Mass.  MDDScores for 33 of the 36 patients indicated the presence of depression, while only eight of the 43 controls had a positive test result.  The average score for patients was 85, while the average for controls was 33.  A second replication phase enrolled an additional 34 patients from the MGH and Vanderbilt, 31 of whom had a positive MDDScore result.  Combining both groups indicated that the test could accurately diagnose major depression with a sensitivity of about 90 percent and a specificity of 80 percent.

“It can be difficult to convince patients of the need for treatment based on the sort of questionnaire now used to rank their reported symptoms,” says Bilello.  “We expect that the biological basis of this test may provide patients with insight into their depression as a treatable disease rather than a source of self-doubt and stigma. As we accumulate additional data on the MDDScore and perform further studies, we hope it will be useful for predicting treatment response and helping to select the best therapies.”

Papakostas adds, “Determining the true utility of this test will require following this small research study with larger trials in clinical settings.  But these results are already providing us with intriguing new hints on how powerfully factors such as inflammation — which we are learning has a major role in many serious medical issues — contribute to depression.”

Over Harvard’s history, researchers and physicians have played key roles in vanquishing disease, from testing and distributing the first American smallpox vaccine in 1800, to the breakthrough in the 1940s that led to a polio vaccine, to the myriad advances of today’s broad-ranging medical research.

In just the past few decades, labs on Harvard’s campuses, at its affiliated hospitals, and in research centers have been the birthplace of key findings against disease, from the 1980s characterization of a frightful condition called AIDS, to new ways of fighting cancer by choking off its blood supply, to pioneering stem-cell-based approaches that use a cell’s innermost secrets to attack degenerative ailments.

Harvard’s disease fighters today share the mission of those who preceded them, but they wield weapons that would be foreign to doctors of yesteryear. They use stem cells to create disease-bearing tissues for lab study, advanced imaging equipment to peek inside the body, genetic techniques that probe a cell’s DNA, and vast statistical databases from which researchers pick out rare anomalies and open doors to understanding.

The list of Harvard’s medical and public health advances includes many vital contributions, from the first use of anesthesia at Massachusetts General Hospital in 1846, to the invention of the iron lung in 1927, to the discovery in the 1950s that vitamin A is essential to vision, to the invention of the heart pacemaker in 1952, to the first human organ transplant in 1954, and many others.

“Harvard has certainly been a leading center for research and therapeutic innovation,” said Scott Podolsky, assistant professor of global health and social medicine at Harvard Medical School (HMS) and director of HMS’s Center for the History of Medicine.

HMS faculty members began fighting disease almost as soon as the Medical School started. In 1800, one of the institution’s first three professors, Benjamin Waterhouse, was the first person in America to test Edward Jenner’s smallpox vaccine, developed in Britain two years earlier.

After reading Jenner’s account of milkmaids’ immunity acquired by a mild infection with cowpox, Waterhouse sent for a sample. He tested it on his 5-year-old son, Daniel, and then inoculated his family and servants. He became a smallpox vaccination advocate, gaining the ear of President Thomas Jefferson.

In the decades to follow, many ailments stalked the American countryside. One, puerperal fever, killed as many as one in five new mothers in European hospitals. In America, where hospital delivery was rare, deaths would follow doctors as they went from delivery to delivery. Caused by streptococci bacteria, it was carried from patient to patient by physicians’ poor hygiene habits in an era before germ theory became standard.

Boston doctor Oliver Wendell Holmes, who was HMS dean from 1847 to 1853, wasn’t the first to suspect puerperal fever was contagious. But his 1843 pamphlet, “The Contagiousness of Puerperal Fever,” went a long way toward convincing a skeptical medical establishment that it was carried by the physicians themselves.

Podolsky said Holmes is an example of another important Harvard medical contribution: skepticism. Holmes pointed out flaws in how things were done at the time, as did a later skeptic, Maxwell Finland, who regularly debunked ineffective antibiotics.

In 1926, HMS faculty members George Minot and William Murphy tackled another deadly ailment: pernicious anemia, which often killed sufferers within three years. Their study showed that a diet heavy in raw liver improved the sufferers’ condition. Later studies isolated the active ingredient, vitamin B12, that today is given routinely. Minot and Murphy, together with George Whipple, shared the 1934 Nobel Prize in Physiology or Medicine for the work.

Even as progress was made against other diseases, polio was a stubborn holdout. Polio could cause paralysis just hours after infection, and, if the paralysis involved breathing muscles, death. Because the disease attacked nerve cells, researchers found it difficult to culture in the lab.

In 1948, HMS Professor John Enders, along with colleagues Frederick Robbins and Harvard School of Public Health Professor Thomas Weller, were trying to grow chicken pox virus in a mixture of human embryonic skin and muscle tissue. In a nearby cabinet was a sample of polio virus, which they decided to try in the new culture. The successful result set the stage for the development of polio vaccines by Jonas Salk and Albert Sabin, and netted Enders, Robbins, and Weller the 1954 Nobel Prize in Physiology or Medicine.

In the early 1980s, the world struggled to understand a mysterious ailment raging through the gay community. In the Harvard lab of Max Essex, researchers were connecting the dots gleaned from his research into feline leukemia, a disease of cats that has startling parallels to human AIDS. Caused by a retrovirus — which carries its genetic information as RNA rather than DNA — feline leukemia often doesn’t cause that actual leukemia but instead suppresses the immune system so other diseases can attack.

Essex, the Lasker Professor of Health Sciences at the Harvard School of Public Health and director of the Harvard School of Public Health AIDS Initiative, was the first, with Robert Gallo, to propose that a retrovirus causes AIDS. His lab contributed several other major findings in AIDS research, including the discovery of GP 120, a protein on the virus’ surface. That finding enabled development of an AIDS screening test, and the protein remains a focus of vaccine research. He also traced the development of HIV in hemophiliacs to HIV-positive blood donors, identified HIV-2, a less virulent strain of the virus mainly found in West Africa, and an HIV analog in other primates called simian immunodeficiency virus, or SIV, which has provided an important laboratory model for how HIV works in the human body.

Today Essex, whose contributions won the 1986 Lasker Award with Gallo and Luc Montagnier, continues to work on AIDS as part of a broader research community that is seeking to understand the human body — healthy and ill — and devise new ways to combat disease.

The answers that have emerged — and are still emerging — are surprising and obvious both. Having a difficult childhood, for example, matters a lot in early adulthood, but its effects fade as the years go by. Among those who had tough beginnings, self-starters who seek out jobs as kids do better than those who don’t. And education — specifically going to college — is more important than money or social status in determining lifetime success.

More recently, the study’s aging subjects have shown that one’s situation at age 50 has more to do with one’s health and happiness at 70 than what happened earlier in life. And surprisingly, the quality of vacations younger in life — a measure of the ability to play — is a better indicator of late-life happiness than income.

The study highlights both controllable and uncontrollable factors that affect healthy aging. While there’s not much someone can do about parents’ social class, early family stability, or ancestors’ longevity, a person certainly has a say over whether to smoke, abuse alcohol, exercise, and keep weight down. The study also highlights the importance of a healthy, stable marriage to late-life happiness and underlines the importance of having mature coping mechanisms for the adversity sure to come.

“We used to think that if you had relatives who lived to a ripe old age, that was the best predictor” of a long life, said Robert Waldinger, director of the Harvard Study of Adult Development, a psychiatrist at Massachusetts General Hospital, and an associate professor of psychiatry at Harvard Medical School. “It turns out that the lifestyle choices people make in midlife are a more important predictor of how long you live.”

Waldinger became director of the Harvard study in 2003, when longtime director George Vaillant stepped down from day-to-day management. To Vaillant, who continues to work on the study, the most important findings concerned the negative effects of alcohol on marital and lifetime success and the evidence that programs like Alcoholics Anonymous work better than other interventions. The study also added nuance to understanding adult development, Vaillant said, which is often thought of as stalling in middle age or peaking at 50 and then declining.

“You only have to think of distinguished 70-year-olds in art and politics to see that something is wrong with that view,” Vaillant said. “Adult development from 30 to 80 certainly takes place. [But] it’s like watching the hour hand of a clock; that’s why it’s not appreciated.”

Waldinger said the study’s central focus now is on marriage, examining how couples have weathered life’s storms and cope with challenges such as declining health and concerns about finances. In recent interviews, researchers asked older couples about conflicts and how they resolve them. But couple after couple, Waldinger said, couldn’t recall conflicts.

“They said, ‘We used to argue about it, but we just don’t anymore,’ ” Waldinger said. “The main developmental task for younger couples is managing conflicts. The main task for older couples is mutual support. … Being in a good marriage buffers you from the effects of pain and disability.”

Both Waldinger and Vaillant have published extensively on the study’s findings. Some of them were published just last year. In a recent paper, Waldinger, Elizabeth Kensinger, and Marc Schulz utilized neural imaging to find that older adults with positive outlooks process emotional information differently from those with more negative views. Vaillant, who has written scholarly articles and several books based on the study, is at work on a history of the study itself.

The research has its roots in a Harvard University Health Services examination of 268 members of Harvard classes between 1939 and 1944. Begun in 1938 and called the Grant Study, it started with exhaustive physical examinations and included regular follow-ups over the years.

The second arm of the study began with Harvard Law Professor Sheldon Glueck, who recruited 456 young men from inner-city Boston neighborhoods between 1940 and 1945 as controls for a study of juvenile delinquency. They were added to the study in the 1970s. Today, just 68 of the Harvard cohort are still alive, many in their early 90s, while 120 of the Glueck Study are alive, most in their early to mid-80s.

Over the decades, subjects have answered biennial questionnaires, allowed health information to be gathered from their doctors, and sat for in-depth interviews. In recent years, they’ve also submitted to neuroimaging scans and given blood for DNA analysis. Researchers have also begun to engage more deeply with their wives, whose reaction, Waldinger said, was, “It’s about time.”

Though the study has led to many publications, Waldinger and Vaillant view the decades of data, interview notes, questionnaires, and videotapes as a barely tapped treasure trove for researchers, providing a rare view of much of these men’s lives. Over the years, researchers have studied the effects of World War II combat, substance abuse, childhood trauma, education, and other factors. To make data easier to access for researchers, Waldinger said, they’ve embarked on a digitization project for the records, currently held in 50 filing cabinets.

“You can search for the word ‘father,’ and the computer will pull out every time that word was used in a man’s life,” Waldinger said.

Vaillant said the study still can surprise, even though he has been involved with the data for 40 years. Just last year, he said, he found that 57 percent of all divorces among Grant Study men involved alcoholism. That statistic had been artificially low until then because, though the men had spoken of their own alcohol problems, many hadn’t been forthcoming about those of their wives until later in life.

“It’s still a treasure trove, and with each passing year more people mine it in different and imaginative ways,” Vaillant said.

In addition to adding new genetic techniques, Waldinger said the researchers are seeking funding to continue the study by enrolling children and even grandchildren, an opportunity rarely replicated. That’s because most longitudinal studies — which follow subjects over long periods — fade after a decade or so because subjects drop out, funding dries up, and researchers move on to new projects. A study lasting as many decades as the Harvard one is a bit freakish, Waldinger said.

“We know how they felt about their parents when they were 19, we know how their parents felt about them, we know what their childhoods were like,” Waldinger said. “It’s so unique, it’ll never be done again.”

A frenzy of movement and laughter ensued, and each iteration of this team-building activity ended in a comical confrontation between two people — just as likely roommates as a professor-student pair. More than just an icebreaker, though, the scene was a primer in human dynamics: a first lesson in engineering design.

For a week in January, 40 students from a variety of backgrounds — comparative literature to computer science — engaged in a “design thinking” workshop led by IDEO, an internationally renowned design consulting firm. Throughout, the human element was key — How do people actually use a product? — as was a certain amount of ad-libbed fun.

By midweek, the second-floor conference room of Maxwell Dworkin looked as though it had been hit by a tornado. Sticky notes covered the walls and dry erase boards, scattered with phrases, concepts, and ideas: “Huge!,” “Turtle backpack,” “Imagination pod,” “Mentor program,” “Kung fu video,” and more. Glue guns, markers, and poster board littered the floor; spaghetti and tape spilled into the adjacent lounge.

The course, “jDesign,” was among many programs available to students during Optional Winter Activities Week, the jam-packed conclusion to Winter Break at the Harvard School of Engineering and Applied Sciences (SEAS).

“Design is about making decisions, often in the face of uncertainty.”

“JDesign” was spearheaded by Gu-Yeon Wei, Gordon McKay Professor of Electrical Engineering and associate dean for academic programs at SEAS, with support from Joseph Zinter, a former design preceptor at SEAS (now at Yale University).

“Design is about making decisions, often in the face of uncertainty,” Zinter said. “It’s like running a race where the course keeps splitting. Each fork is a decision.”

“The good designer adheres to a process — a set of tools and techniques that guides them in the decision-making process,” Zinter said. “JDesign is about teaching those tools and techniques.”

Students were assigned to seven groups and asked to create and present a “starter kit” for a person with some goal. One group decided to make a toolbox for a high school graduate transitioning to college; another designed items that the homeless of Harvard Square could use to stay warm during harsh winters.

Throughout the design process, each team was urged to consider human factors; one team devised a lovable stuffed turtle to help an overwhelmed sophomore select a concentration at Harvard.

Intertwined with formal presentations by IDEO on topics such as human-centered design and visual thinking were brainstorming sessions, role-playing games, construction projects, and man-on-the-street interviews.

Siyabulela Xuza ’12, a South African student who participated in the course, noted the impact that the workshops had on him as an aspiring engineer.

“Academically, it’s given me a paradigm shift,” he said. “I’ve been given tools to know how to approach problems by considering human factors — putting humans at the center, and also really asking myself questions about the day-to-day things that we do.”

“I came in here thinking that I knew how to design on the world, imposing solutions,” Xuza added, “but learning about humans throughout the design process taught me how to design in the world.”

Emi Nietfeld ’15, a freshman with an artistic background, particularly enjoyed the opportunity to program using Arduino, a hardware-software combination designed for people at all skill levels.

“It was awesome to see that there’s this whole world out there just meant to empower people to build stuff,” she said. “I really like that we had ideas and made them right away.”

The workshop was led by David Goligorsky and other IDEO employees and facilitated by graduate students from SEAS and the Harvard Graduate School of Design (GSD). The faculty and facilitators integrated seamlessly into the design teams, learning just as much from their energetic teammates as they contributed in expertise.

Wei hopes that the inaugural workshop will continue to inspire “channeled innovation” in the students who participated.

“I was really impressed by the creativity and the energy,” he said. “Everyone evolved throughout the week from what they thought they were going to work on, on day one, to what they actually ended up working on and presenting on day five. I’m hoping we can all take what we learned throughout this week and apply it to what we do, whether it be research, whether it be courses, [or] continuing on to design new projects.”

The workshop pushed beyond the traditional perception of engineering as a math-centric, technical domain, emphasizing that effective engineering design is informed by (and resides within) the context of the humanities and social sciences.

Said Nietfeld: “There’s the product side of things, and there’s the story side of things, and we did both [during jDesign], but the story was so important. You could’ve had a loaf of bread, and if you told the right story about it, everybody would be like, ‘Oh my God, that’s so cool — it’s a loaf of bread!’”

“For an engineering program, jDesign was pretty progressive,” said Zinter. “SEAS is pushing hard against the conventional engineering paradigm, and that’s pretty rad.”

Besides Wei, Zinter, and Goligorsky, major contributors to the course were Brad Crane (GSD/IDEO), Jawn Lim (GSD), Faye Hayes (GSD), Nathan King (GSD), Avi Uttamchandani (design preceptor at SEAS), Conor Walsh (assistant professor of mechanical and biomedical engineering at SEAS), and Beth Altringer (visiting lecturer on innovation and behavior at SEAS).

The course was supported by the Harvard President’s January Innovation Fund for Faculty.

The remarks were part of the keynote address delivered by Hammonds at MIT’s Institute Diversity Summit. The annual conference provides an opportunity for students, faculty, and staff to learn about and discuss ways to promote excellence and diversity at the school.

Hammonds, the Barbara Gutmann Rosenkrantz Professor of the History of Science and of African and African American studies, said that women and people of color had demonstrated time and again their interest in science, technology, engineering, and mathematics (STEM), as well as their ability to succeed in these fields. Scientists agree that race and gender should not determine whether a student pursues a career in STEM. So why, she asked rhetorically, do women, Latinos, African-Americans, and Native Americans continue to be underrepresented in these areas of study?

To shed light on the question, Hammonds called on the work of the African-American intellectual, scholar, and activist W.E.B. Du Bois. Du Bois, she said, was the first to name and identify the ‘diversity problem’ in science in his 1939 essay “The Negro Scientist.” The piece was a response to the statements by a prominent white American scientist who had publicly noted how few African-Americans had made their mark in science.

“The scientist had stated that Negroes — the preferred term of the period — had made their mark in music, literature and on the stage but not in the exact sciences,” she said. “Du Bois’ response called the man’s attention to the fact that it was not easy for an American Negro to pursue science.  Though the man publicly agreed with Du Bois’ point, privately he expressed to him ‘… that the exact and intensive habit of mind, the rigorous mathematical logic demanded of those who would be scientists [was] not natural to the Negro race.’”

To disprove this opinion, Du Bois discussed the careers of the 12 African-American male scholars listed in American Men of Science. Although the men had been educated at some of the most prestigious schools in the country — including Harvard, Yale, Brown, Bowdoin, the University of Chicago, and Williams — their careers had been curtailed because of “color prejudice,” or racism.

“In each instance, Du Bois described men who were well-educated, serious scholars and researchers,” Hammonds said. “They published in the leading journals in their fields and strived to attain positions in major institutions. Yet, in each case they were denied permanent positions for which they were qualified.  In many instances, their work was well regarded, and on that basis alone these men were sometimes offered prominent positions in the academy — only to be denied employment when ‘it was learned by correspondence or interview that they were colored.’”

Du Bois also gave examples of discriminatory treatment toward graduate students, Hammonds said, including that of an African-American student who was denied a fellowship because his teacher believed that he would not be able to find work after studying science. Others were denied doctorates only on the basis of their color even after passing their general examinations. Young African-American scientists could sometimes find work in the historically black colleges and universities (HBCU), but these institutions typically had no laboratories, no museums, and no scientific collections.

“Here in 1939, on the eve of World War II, Du Bois offered a powerful analysis of the ‘diversity problem’ in science,” Hammonds said. “He located that problem in the social context of the United States where legalized segregation constrained the opportunities of African-Americans who had the desire, the ability, and the education to do science.  More importantly, he asserted that the prejudice of white scientists was connected to the pervasive view that ‘the exact and intensive habit of mind, the rigorous mathematical logic demanded of those who would be scientists is not natural to the Negro race.’”

African-American women faced even greater barriers to participation in science than their male counterparts, Hammonds said. Before World War II, there were only eight African-American women with Ph.D.s in science in the United States, compared with nearly 20,000 white men. All secured positions at historically black colleges, but, in addition to the lack of resources that plagued their male counterparts, the women encountered negative attitudes about gender roles that limited their advancement even within those institutions. Hammonds, who received a master’s degree in physics from MIT, commended the institution as one of the few in the country with a history of educating African-American women scientists. Even so, she said, the opportunities were few and far between.

“The first African-American female graduated from MIT in 1902,” she said. “The second was in the 1950s; during the late 1960s MIT admitted only one or two African-American women a year. Significant numbers of women from this group were not admitted until the 1970s. The first African-American woman was appointed to the faculty in the 1970s; the first one tenured through the ranks in 1998; and the first African-American female faculty in the school of engineering was tenured just this year. As you can see, the barriers within science have persisted for minority women even as they changed for white women and minority men.”

Hammonds made a plea for continued study of the issue of diversity in science and engineering. It is critical to better understand how scientific communities work and how talent is recognized, valued, and assessed, she said. To illustrate why, Hammonds closed her talk with a final quote from Du Bois.

“One may say in answer to all this: so what?  After all, there are plenty of white men who can be trained as scientists.  Why crowd the field with Negroes who certainly can find other socially necessary work?  But the point is that ability and genius are strangely catholic in their tastes, regard no color line or racial inheritance.  They occur here, there, everywhere, without rule or reason.  The nation suffers that disregards them.  There is ability in the Negro race — a great deal of unusual and extraordinary ability, undiscovered, unused and unappreciated.  And in no line of work is ability so much needed today as in science.”

“My grandfather pulled the short stick, so he had to be the test pilot on that glider without much knowledge,” recalls T. Fettah Koşar, a principal scientist and facilities manager at Harvard’s Center for Nanoscale Systems. “He didn’t have a license — had been on planes, but I used to hear stories about how he was so nervous.”

“But he flew and landed without any trouble.”

That’s the story Koşar grew up with, first as an aspiring astronaut, then as a budding pilot, following in his grandfather’s footsteps. From the age of 5, he built model airplanes from balsa wood and read aviation magazines.

“I never got my license,” Koşar’s role model would tell him, at home in Turkey. “I hope one day you’ll be able to do that — to do what I couldn’t do.”

Today, in the United States, Koşar is a certified (licensed) pilot, sharing his passion for flight with the community around him, just as his grandfather did.

Ismail Tursan (far right) stands in front of the Kleopatra, a glider he built with his friends and flew in 1934. Tursan's grandson, T. Fettah Koşar, now works at Harvard's Center for Nanoscale Systems. Photo courtesy of T. Fettah Koşar

A course in flight takes off

January at Harvard is a time of intellectual excitement — of investment in personal interests and growth. In the weeks between semesters, students have the opportunity to participate in a vast range of optional workshops, mini-courses, field trips, training sessions, and seminars, all made possible by the passion and dedication of the University’s faculty and staff.

Koşar, with the support of the Center for Nanoscale Systems, arranged and taught a three-day mini-course on the fundamentals of aerodynamics. Offering far more than just a classroom introduction to the physics of flight, however, Koşar treated students to one-on-one time in the cockpit of a rented plane, high above the snowy, coastal landscape of northeastern Massachusetts.

“It was an amazing feeling to fly in a small plane where you can see what exactly is going on,” says Pakpong Chirarattananon, a graduate student in electrical engineering at Harvard School of Engineering and Applied Sciences (SEAS). Chirarattananon is a member of the Harvard Microrobotics Laboratory, where his research in control systems and robotics involves designing the flapping-wing mechanism of a micro-air vehicle.

“We were even given a chance to take control of the plane for a brief period,” Chirarattananon adds. “In the meantime, the exercise was a brilliant demonstration of results we expected to see according to physical laws.”

Before takeoff, the students taped strands of yarn onto the wings of the plane in order to visualize the airflow during a stall.

“It’s like free fall,” Koşar explains, lifting a model airplane in the classroom. “You reach the point where the wing is not generating enough lift, and it goes down like this” — he drops his hand — “and all those strings start to do chaotic things instead of being nicely aligned with the air flow.”

Several other in-flight exercises helped to bring theory to life. The students explored how the position of the wing flaps affected the stall speed and, with a kitchen scale, measured and calculated how the angle of a turn affected the G forces.

Koşar also showed his students the facilities where enthusiasts can build their own planes — not with wood, these days, but with aluminum and fiberglass.

“It was great fun,” says Matthias Lorenzen, a visiting graduate student in mechanical engineering at SEAS who went up in the plane. “It is a mixture of the feeling you have when you leave the ground and the great view that makes flying so interesting. Clouds suddenly become something three-dimensional; you can nearly touch them.”

Two dreams

An engineer by training, Koşar earned his bachelor’s degree in chemical engineering at Boğaziçi University in Istanbul. He pursued graduate studies in the United States, receiving master’s degrees first in chemical engineering and materials science at the University of California, Davis, and then in bioengineering at the University of Washington.

A career in engineering, however, was not his only goal, and in 2000 he began his first training as a pilot.

“Flying over Seattle, over the sea, and seeing the mountains, it was really nice,” he recalls.

But aviation is not a cheap hobby, and the demands of Koşar’s continuing graduate studies forced him to postpone his dream. He graduated from the University of Washington in 2005 with a Ph.D. in bioengineering and nanotechnology, as well as a certificate in technology entrepreneurship — but still no pilot’s license.

In 2006, Koşar arrived at the Center for Nanoscale Systems, a research facility maintained by Harvard’s Faculty of Arts and Sciences and supported by the National Science Foundation. While working as a specialist in soft lithography, and later as manager of the Material Synthesis and Characterization Facility, he became eligible for tuition assistance (TAP) benefits.

That changed everything. Koşar enrolled in an online course in aerodynamics from Embry-Riddle Aeronautical University, immediately thinking, “I should offer this at Harvard.”

He restarted his flight training at Beverly Municipal Airport in Danvers, Mass., and in October 2011, he made his 98-year-old grandfather proud, finally earning his pilot’s certification.

For Koşar, it is just a hobby, but it’s also a passion. On the weekends, when he’s not flying to Nashua “for a $100 omelet,” he’s flying radio-controlled model planes in a park in Burlington, Mass., with other enthusiasts and kids.

And Koşar kindles that same excitement in his students, several of whom hope to become pilots.

“It has always been my dream to operate a real airplane,” says Xiao Guo, a graduate student in computer science at SEAS who took the January mini-course. “When I flew in the sky, I forgot all the pressure in my life and just focused on the flight.”

Today, the Experiment Fund, a new seed-stage investment fund, opens its doors with backing from storied venture capital firm New Enterprise Associates (NEA). Designed specifically to support student start-ups and nurture novel technologies and platforms created in Cambridge (or by innovators educated in Cambridge), the Experiment Fund will eventually include additional strategic angel investors and advisers.

“We are very excited about the Experiment Fund; we believe it will provide a much-needed set of people, skills, and financial resources to spur the innovation and idea creation of our students,” says Cherry A. Murray, dean of the Harvard School of Engineering and Applied Sciences (SEAS).

Murray, who helped to realize the fund, will designate SEAS faculty members to advise student entrepreneurs about the Experiment Fund and other available opportunities and resources, such as the new Harvard Innovation Lab (i-lab).

The idea to provide an intensely local company-building resource to young innovators originally grew out of close collaboration between venture capitalist Patrick Chung, academic and entrepreneur David Edwards, and scholar-turned-entrepreneur Hugo Van Vuuren.

“Cambridge has always seeded and cultivated brilliant minds and entrepreneurs, and now they’ll have another reason to stay rooted in and draw strength from these fertile soils,” says Chung, who is co-head of NEA’s consumer and seed-stage investing practices.

Chung received his A.B. degree in environmental science from Harvard College and a joint J.D.-M.B.A. degree from Harvard Law School and Harvard Business School.

“Students will have an obvious place to go once they breach the boundary of the classroom,” adds Edwards, Gordon McKay Professor of the Practice of Biomedical Engineering at SEAS and founder of Le Laboratoire in Paris.

“We are very excited to work with everyone on campus to infuse the fund with our global platform and entrepreneur-first tradition,” says Harry Weller, general partner at NEA and graduate of Harvard Business School.

Van Vuuren, a 2007 graduate of Harvard College, student at the Harvard Graduate School of Design, and fellow at the Berkman Center for Internet & Society at Harvard, adds, “The fund is looking for smart and resourceful people, zealous full-time teams, and experiments in need of seed funding and hands-on help to get off the ground.”

Designed to attract engineers, entrepreneurs, and designers and to empower them to test and build bold ideas, the Experiment Fund will explore three core areas: Information, health care, and energy technologies.

Chung, who serves as an expert-in-residence at SEAS, expects the fund to support several promising companies in the coming two years. Each new venture will receive up to $250,000 over that same period.

While the fund expects to cultivate student innovation initially at Harvard, it will function completely independently of the University and will invest broadly on the East Coast.

This grant will allow the scientific community to expand its understanding of how biological decisions are made in health and disease, paving the way for major treatment breakthroughs.

“Creating a complete catalog of cell circuitry will ultimately have a huge impact on our ability to understand and treat disease,” said Broad Institute Director Eric Lander. “The Klarmans are laying the foundation for what I predict will grow eventually into a worldwide effort, with the same spirit and vision of the Human Genome Project. This is a bold step by two extraordinary philanthropists.”

The grant will launch the Klarman Cell Observatory at the Broad Institute, which will foster groundbreaking discoveries and technological advances in cell circuit research. It will continue to propel advances in the experimental and computational methods needed to understand cell circuitry, and establish their broad applicability by studying a variety of cell types. Moreover, observatory researchers will partner with researchers across the Broad and around the world to pursue collaborative projects that shed light on the inner workings of these cells.

Beth Klarman, president of the Klarman Family Foundation, said, “The Cell Observatory has the potential to foster insights into so many different aspects of health and disease, including the biological basis for behavioral health. We feel that providing this funding to the Broad, an institution whose model of collaboration accelerates innovation, is the best way to positively impact the greatest number of people.”

Much of what is currently known about cell circuits emerged from decades of research on single-celled organisms, such as yeast and bacteria. The cells of more complex beings, such as humans and other mammals, have been much more difficult to study in part because their circuits are more elaborate. Researchers have worked on the problem, of course, but the typical approach—deciphering a single component or connection at a time—has been a slow and piecemeal process, in part because the tools and knowledge needed to comprehensively crack mammalian cell circuits have only recently become available.

The Klarman Cell Observatory will be led by Broad Institute core member Aviv Regev, who has pioneered a new paradigm for defining cellular circuitry. Over the past five years, Regev and her colleagues have made significant strides in systematically deciphering the circuits of two key human cell types: dendritic cells, a type of immune cell, and the stem cells that give rise to blood cells. This work not only shed light on the cells’ biology and the systems in which they function, but it also served as a proof-of-principle for how to approach such projects on a large scale.

“Our work has shown that you can choose one cell type and very systematically—one layer at a time—decipher its circuits,” Regev said. “I’m truly grateful to the Klarmans for their visionary support, which will allow us to move this early proof-of-concept work to the next critical phase.”

The Cell Observatory will pursue a range of collaborative projects by partnering with scientists within the Broad community and beyond. A critical component of the observatory’s work will involve collaborations with scientists in Israel, including training opportunities for junior scientists. Researchers in that country are renowned experts in the cell circuitry of single-celled organisms and established many of the initial methods used to decipher them.

Seth Klarman, chairman of the Klarman Family Foundation and Broad Institute board member, said, “Beth and I are thrilled to support this groundbreaking effort. It requires not only deep scientific expertise, but also the ability to draw researchers together from various institutions and disciplines. Through my involvement on the Broad’s board, I have developed an even greater appreciation of the fact that scientists are on the verge of critical breakthroughs, and there’s really no other place to do this kind of work than the Broad.”

The study appears in the Jan. 25 issue of the Journal of the American Medical Association (JAMA).

“Routine childhood immunizations are a mainstay of modern disease prevention. The negative impact on childhood vaccinations from PFCs should be viewed as a potential threat to public health,” said Grandjean, adjunct professor of environmental health at HSPH and the report’s lead author.

PFCs have thousands of industrial and manufacturing uses. Most Americans have the chemical compounds in their bodies. Prior studies found that PFC concentrations in mice similar to those found in people suppressed immune response, but the adverse effects on people had been poorly documented.

The researchers analyzed data on children recruited at birth at National Hospital in Torshavn, Faroe Islands, 1999-2001. A total of 587 participated in follow-up examinations. Children were tested for immune response to tetanus and diphtheria vaccinations at ages 5 and 7 years. PFCs were measured in maternal pregnancy serum and in the serum of children at age 5 to determine prenatal and postnatal exposure.

The results showed that PFC exposure was associated with lower antibody responses to immunizations and an increased risk of antibody levels in children lower than those needed to provide long-term protection. (Antibody concentrations in serum are a good indicator of overall immune functions in children.) A twofold greater concentration of three major PFCs was associated with a 49 percent lower level of serum antibodies in children at age 7.

“We were surprised by the steep negative associations, which suggest that PFCs may be more toxic to the immune system than current dioxin exposures,” said Grandjean.

The PFC concentrations were similar to or slightly below those reported in U.S. women, and most serum PFC levels in Faroese children at age 5 were lower than those measured in U.S. children aged 3 to 5 in 2001-2002.

The study was supported by the National Institute of Environmental Health Sciences, the U.S. Environmental Protection Agency, the Danish Council for Strategic Research, and the Danish Environmental Protection Agency.

Ancient humans may not have had the luxury of updating their Facebook status, but social networks were nevertheless an essential component of their lives, a new study suggests.

The study’s findings describe elements of social network structures that may have been present early in human history, suggesting how our ancestors may have formed ties with both kin and non-kin based on shared attributes, including the tendency to cooperate. According to the paper, social networks likely contributed to the evolution of cooperation.

“The astonishing thing is that ancient human social networks so very much resemble what we see today,” said Nicholas Christakis, professor of health care policy at Harvard Medical School and professor of sociology in the Harvard Faculty of Arts and Sciences, and senior author on the study. “From the time we were around campfires and had words floating through the air, to today when we have digital packets floating through the ether, we’ve made networks of basically the same kind.”

“We found that what modern people are doing with online social networks is what we’ve always done — not just before Facebook, but before agriculture,” said study co-author James Fowler, professor of medical genetics and political science at the University of California, San Diego, who, with Christakis, has authored a number of seminal studies of human social networks.

The findings will be published Jan. 26 in Nature.

Roots of altruism

The natural world, red in tooth and claw, has a gentle side. While individuals compete fiercely to ensure the proliferation of their progeny, a few animals, including humans, also cooperate and act altruistically. Researchers have wondered if human social networks are a product of modern lifestyles, or if they could have emerged under the kind of conditions that our distant ancestors faced. This question has been challenging for classic evolutionary theory to explain neatly.

For cooperation to arise, an altruistic act, like sharing food with a nonrelative, must have a net benefit for the sharers. Otherwise, purely self-serving individuals would outcompete and eventually replace the selfless. All theoretical explanations for the evolution of cooperation — kin selection, reciprocal altruism, group selection — rely on the existence of some system that allows cooperators to group together with other individuals who tend to share.

“If you can get cooperators to cluster together in social space, cooperation can evolve,” said Coren Apicella, a postdoctoral research fellow in Health Care Policy at Harvard Medical School and first author on the paper. “Social networks allow this to happen.”

While it is not possible to quiz our distant ancestors about their friendships or habits of sharing and collaborating, a team of researchers from Harvard Medical School, the University of California, San Diego, and the University of Cambridge have characterized the structure of social networks among the Hadza, an ethnic group in the Lake Eyasi region of Tanzania, one of the last surviving groups of hunter-gatherers. (There are fewer than 1,000 Hadza left who live in the traditional way.)

Getting connected

The Hadza lifestyle predates the invention of agriculture. The Hadza eat a wide range of wild foods, foraging for tubers, nuts, and fruit and hunting a great variety of animals, including flamingos, shrews, and giraffes. Honey is one of their favorite foods, known by half a dozen different names in Hadzane, their primary language.

Apicella took the lead in collecting the data for the study, interviewing 205 adult Hadza over the course of two months, measuring their tendency to cooperate and mapping their friendships.

Apicella, Fowler, and Christakis designed the study and experiments, working with Frank Marlowe, lecturer in the Department of Archaeology and Anthropology of the University of Cambridge, and author of the only book-length ethnography on the Hadza in English.

Collecting the data was not easy. The nomadic Hadza roam over 4,000 rugged square kilometers. Apicella and her research assistants traveled the region by Land Cruiser battling mud-drenched trails — at one point forcing her and her colleagues to pave the ground with felled trees — and, on an earlier trip, even fleeing a horde of marauding elephants.

“The astonishing thing is that ancient human social networks so very much resemble what we see today,” said Harvard Professor Nicholas Christakis, senior author on the study. File photo Jon Chase/Harvard Staff Photographer

In order to construct a social network, Apicella and her colleagues took a dual approach. First, they asked Hadza adults to identify individuals they would prefer to live with in their next encampment. Second, they gave each adult three straws of honey and told them they could give these straws as gifts to anyone in their camp. This generated 1,263 campmate ties and 426 gift ties.

In a separate activity, the researchers measured levels of cooperation by giving the Hadza additional honey straws that they could either keep for themselves or donate to the group.

When the networks were mapped and analyzed, the researchers found that cooperators and noncooperators formed distinct clusters.

The researchers also measured the connectedness of people with similar height, age, handgrip strength, etc., and other characteristics, such as food preference. They also analyzed the transitivity of friendship — the likelihood that one’s friends are friends with one another, and other network properties.

The structure and dynamics of the Hadza hunter-gatherer social networks were essentially indistinguishable from existing social network data drawn from modern communities.

“We turned the data over lots of different ways,” said Fowler. “We looked at over a dozen measures that social network analysts use to compare networks, and pretty much, the Hadza are just like us.”

“Human beings are unusual among species in the extent to which we form long-term, nonreproductive unions with other members of our species,” said Christakis. “In other words, not only do we have sex, but we also have friends.”

Previous work by Christakis and Fowler, who are co-authors of the book “Connected,” has shown that our experience of the world depends on where we find ourselves within social networks. Particular studies have found that networks influence a surprising variety of lifestyle and health factors, such as how prone you are to obesity, smoking cessation, and even happiness.

For the researchers, the Hadza offer strong new evidence that social networks are a truly ancient, perhaps integral part of the human story.

This research was funded by the National Institute on Aging and by the Science of Generosity Initiative of the University of Notre Dame.

Through experiment and mathematical analysis, researchers have shown that the extracellular matrix (ECM), a mesh of proteins and sugars that can form outside bacterial cells, creates osmotic pressure that forces biofilms to swell and spread. The ECM mechanism is so powerful that it can increase the radius of some biofilms fivefold within 24 hours.

The results have been published in the Proceedings of the National Academy of Sciences.

Biofilms, large colonies of bacteria that adhere to surfaces, can be harmful in a wide range of settings, causing tooth decay, hospital infections, agricultural damage, and corrosion. Finding ways to control or eliminate biofilms is a priority for many industries.

In order for a biofilm to grow, a group of bacterial cells must first adhere to a surface and then proliferate and spread. When a vast number of cells are present, this can translate into the creation of a filmy surface spanning several meters.

“Our work challenges the common picture of biofilms as sedentary communities by showing how cells in a biofilm cooperate to colonize surfaces,” says lead author Agnese Seminara, a research associate at the Harvard School of Engineering and Applied Sciences (SEAS).

Several types of biofilms have been characterized based on composition and antibiotic resistance, but until now it has not been clear what roles the whiplike flagella and the ECM play in the outward movement of cells.

While the presence of a flagellum has traditionally been associated with greater movement capability, the new research has found that a flagellum actually confers little advantage in the formation of biofilms. In the Harvard study, mutant bacteria lacking flagella were able to spread at almost the same rate as the wild-type (natural) ones. Mutants that could not secrete the ECM, however, showed stunted growth.

The team of physicists, mathematicians, chemists, and biologists examined the formation of biofilms in Bacillus subtilis, a type of rod-shaped bacteria often found in soil. Their focus on this particular species was led by Roberto Kolter, professor of microbiology and immunobiology at Harvard Medical School and an expert on biofilms and the genomics of B. subtilis.

“This project establishes a link between the phenotype, the physically observable traits of biofilm growth, and the genetic underpinning that allows spreading to happen in B. subtilis,” said co-principal investigator Michael Brenner, the Glover Professor of Applied Mathematics and Applied Physics at SEAS.

The researchers had speculated about a possible connection between the biofilm’s quest for nutrition and the process of spreading. Because biofilms absorb nutrients through their exposed surface area, they can only swell vertically to a certain point before the surface-area-to-volume ratio makes it impossible to adequately nourish every cell. At this point, the biofilm must begin to spread outward so that the surface area increases along with the number of cells.

The ECM, a complex mesh of proteins, sugars, and other components outside of the individual cells, holds the key to one aspect of this movement: it apparently increases osmotic pressure within the biofilm.

In response to the increased pressure, the biofilm immediately absorbs water from its surroundings, causing the entire mass to swell upward. The final change in the shape of the biofilm is due to a combination of this swelling and the horizontal spreading that follows.

Seminara and Brenner created a mathematical model that mirrored many of the team’s physical observations. The model supported the experimental observations; by considering the relationship between swelling and spreading, they were able to find the “critical” time at which horizontal outward motion begins.

“This work is led by theoretical predictions which were tested by experiment and proved to be correct,” said co-principal investigator David Weitz, Mallinckrodt Professor of Physics and Applied Physics at SEAS and co-director of the BASF Advanced Research Initiative at Harvard. “The results also demonstrate how simple physical principles can provide considerable insight into the behavior of biofilms.”

The motion of biofilms represents only a small part of a complex subject. Further research will investigate how biofilms adapt and possibly manipulate their environment. The ultimate goal is to alter biofilms’ behavior to minimize their harmful effects.

“The natural question at this point is: do cells actively control biofilm expansion and can they direct it toward desired targets?” said Seminara. “This is a first step toward understanding the striking evolutionary success of these ubiquitous organisms, and it may open the way to unconventional methods of biofilm control.”

Seminara, Brenner, and Weitz worked with Thomas Angelini, an assistant professor at the University of Florida and a former member of the Weitz lab; James Wilking, a SEAS research associate in applied chemistry; Senan Ebrahim ’12, an undergraduate at Harvard; and Kolter and Hera Vlamakis of Harvard Medical School.

The research was supported by the BASF Advanced Research Initiative at Harvard, the Seventh European Community Framework Programme, the National Institutes of Health, and the Harvard Materials Research Science and Engineering Center, which is supported by the National Science Foundation.

The paper is available here.

“I got caught up in the new experience of college,” she said. “You forget about sleep and eating healthy because you think about the friends you make and the activities you can go to. Then you kind of get away from the routine that allows you to experience everything and still stay healthy.”

Nyambi and dozens of her classmates started 2012 with a new emphasis on wellness, thanks to the Optimal Health program held over Wintersession at the Fong Auditorium. Sponsored by the Center for Wellness and Harvard Athletics, Optimal Health touched on all the major aspects of prevention, with presentations from a lifestyle medicine consultant, a nutritionist, a sleep specialist, and other experts.

“We were very excited to have different professionals from around the University come and talk to students about optimal health,” said Jeanne Mahon, director of the Center for Wellness. “We tried to put together an afternoon of workshops that were both educational and fun.”

First up was Elizabeth Frates ’90, the energetic director of medical student education at Boston’s Institute of Lifestyle Medicine. Frates had students fill out a wellness wheel and rank on a scale of 1 to 10 the importance of friends, fun and recreation, sleep, nutrition, exercise, and other aspects of physical and mental health. Using the same scale, she had the students rate the amount of energy they were putting into each area. When they compared the two ratings, most in the crowd found that they weren’t putting a lot of time and effort into the aspects of wellness that were most important.

In response, Frates spoke to students about P.A.V.I.N.G. a path to wellness. “Physical activity [P] is a critical piece of wellness,” she said. “So is our attitude [A] and beliefs. It’s important to keep a variety [V] in all aspects of our life, whether physical activity or nutrition. You can’t keep working off old information about health, so constant investigation [I] is key. In the 1980s, for instance, fat was the enemy. Today, it’s sugar. Good nutrition [N] means a focus on fruits and vegetables, whole grains, healthy proteins, and fiber. And when you’re on a wellness journey, you have to continue to have concrete goals [G].”

To show students how easy it can be to integrate wellness into their lives, she had the group stand up and join her in jogging vigorously in place for two minutes. If many of the students were a little out of breath at the finish, they also felt invigorated and got the message that an expensive gym membership wasn’t a prerequisite for fitness.

“You can do things that don’t necessarily take you to the shower,” Frates said. “It’s great to work out and to take the hour, but you can also practice a little lifestyle medicine and get physical activity during the day.”

Next, Harvard University Health Services (HUHS) nutritionist Yeemay Su Miller gave students a primer on healthy eating. She listed the top three diseases in the United States — heart disease, cancer, and stroke — and said preventing each was heavily influenced by diet. The good news, she told the crowd, is that research shows it’s possible to change one’s sense of taste over time to prefer more healthy foods, such as whole grains, fruits and vegetables, and lean protein.

“We know fruits and vegetables are preventative for disease,” she said. The recommended 7 to 13 servings a day may seem like a lot, but it’s doable. If you don’t smoke and you get exercise, then good health really comes down to nutrition.”

Miller recommended that students eat smaller meals 4 to 5 times a day. Downsizing meal size prevents postprandial sluggishness, she said, and increased frequency ensures that the brain always has the glucose it needs for optimal function.

Her final advice was for students to be mindful when eating.

“Let eating be a pure pleasurable activity,” she said. “Engage all of your five senses. Don’t do work, watch TV, or surf the Web. Just eat.”

When Miller was done, Wellesley College’s Catherine Collins came in to help students get some sleep. She asked undergraduates how much rest they typically get each night. Most said that they slept only 4 to 6 hours, significantly less than the 7 to 9 hours necessary for optimal health.

“Sleep is something that is not extra,” Collins said. “It’s important for your academic health and well-being. What happens is that all you learn during the day gets synthesized when you go to sleep. Research shows that if you learn something new and want to be able to apply it, you really need to sleep.”

Collins gave students tips on getting good rest: Turn off the television or computer at least an hour before bed to give the body time to produce melatonin, the hormone that creates drowsiness; keep a “worry pad” by the bed for middle-of-the-night concerns about work; avoid alcohol, nicotine, and heavy exercise for 3 to 6 hours before bed. She also gave students advice on what to do when sleep won’t come.

“If you haven’t fallen asleep in 20 minutes, leave your bed. Read, doodle, crochet, or do something to take your mind off of what’s keeping you from falling asleep. If you don’t get 7 to 9 hours a night, a 20- to 30-minute nap can be restorative, and a 90-minute nap on the weekend can eat away at sleep debt.”

The afternoon’s program wrapped up with a quick tutorial on stress management from HUHS outreach nurse Lois Badwan, who gave students some simple advice on staying calm and happy.

“Find 15 to 30 minutes a day to shut off your cellphones, BlackBerries, etc.,” she said. “Eat well. Exercise daily. Talk to a friend. Above all, take time to laugh.”

Before moving into the lobby of Boylston Hall with her classmates to chat about wellness and to nosh on healthy snacks after the program, Jasmine Gipson ‘15 said she appreciated Optimal Health’s focus on active steps and practical information.

“They didn’t just spout a lot of facts,” she said. “They named resources on campus that could help — where the gyms were; what classes they offered; what the schedule is; what’s in the cafeteria; and what you should put on your plate. It was very specific to Harvard.”

Nyambi said Optimal Health will help her to resume many of the good habits she had when she arrived at Harvard.

“I was passionate about nutrition and living healthy in high school,” she said. “I wanted to continue at Harvard, but found in the fall that I had gotten away from wellness. This program was a good segue to changing things around and getting back to the way I was.”

“We found that labeling all foods and beverages with a simple red, yellow, and green color scheme to indicate their relative healthiness led patrons to purchase more of the healthy and fewer of the unhealthy items,” said Anne Thorndike of the MGH division of general medicine, who led the study.  “We also found that moving items around to make the healthy items more convenient and visible led to further improvement in the nutritional quality of items purchased.”

Thorndike is an assistant professor of medicine at Harvard Medical School.

The authors note that most point-of-purchase efforts to encourage more nutritious choices focus on labeling the calorie content of food, which will soon be required for many restaurants and food service vendors as part of the Patient Protection and Affordable Care Act. However, calorie information is only useful if people read and comprehend it — which requires understanding their own calorie needs, accurately estimating serving sizes, and having enough time to consider and act on the information provided.  Studies by psychologists and behavioral economists have noted that individuals tend to maintain their typical behavior patterns and are more motivated by actions with immediate, rather than long-term, rewards.

The research team — including leaders of the MGH Nutrition and Food Services — devised a two-phase plan.  In the first, which began in March 2010, color-coded labels were attached to all items in the main hospital cafeteria — green signifying the healthiest items, such as fruits, vegetables, and lean meats; yellow indicating less healthy items; and red for those with little or no nutritional value.  Signs in the cafeteria encouraged customers to consume green items often, to consume yellow items less often, and to consider other choices for red items. Cash registers were programmed to record and identify each purchased item as green, red, or yellow. Additional nutritional information was made available in the cafeteria throughout the six-month study period.

For the second phase, which began in June 2010, displayed food items were rearranged according to principles of behavioral economics. This phase focused on cold beverages, premade sandwiches, and chips — popular items likely to be purchased by customers who have little time to spend and may be more influenced by location and convenience. Refrigerators were arranged to place water, diet beverages, and low-fat dairy products at eye level, while beverages with a red or yellow label were placed below eye level.  The sandwich refrigerator was also arranged to put green items at eye level while red or yellow items were placed above and below.  Racks of chips had yellow items at eye level and red items below, and additional baskets of bottled water were placed near stations where hot food was served.

At the end of the study period, sales of green items had increased significantly, while sales of red items decreased.  During the first phase, sales of all red items decreased 9.2 percent — with red beverage purchases dropping 16.5 percent — while green item sales increased 4.5 percent, with a 9.6 increase in green beverages.  In the second phase, red item sales dropped another 4.9 percent compared with the first phase, with beverages dropping by 11.4 percent; and while sales of green items decreased 0.8 percent in the second phase, sales of green beverages increased another 4.0 percent.  A comparison with two satellite cafeterias where these measures had not been instituted revealed that these changes were much more pronounced in the cafeteria where the study was conducted.

“We believe this intervention was so successful because it was simple and easy to understand quickly.  The labeling did not require any special skills and could be easily interpreted when a customer was in a rush,” said Thorndike.  “Any of these strategies could be easily translated to other food service environments.”

All elements of the program remain in place, said Thorndike, with the color-coded labeling extended to other MGH food service locations. Future analysis is planned to see whether the changes are maintained over time.

Co-authors of the report — which was supported by the National Center for Research Resources and the National Heart, Lung and Blood Institute — are Lillian Sonnenberg and Susan Barraclough, MGH Nutrition and Food Services; Douglas Levy, Mongan Institute for Health Policy at MGH; and Jason Riis, Harvard Business School.

Jayawardhana, a fellow at the Radcliffe Institute for Advanced Study this year, said that understanding of the Milky Way has advanced dramatically since the early 1990s, when the only known planets in the galaxy were those circling the sun.

From its incremental beginnings, the search for planets around other stars, dubbed extra-solar planets or “exoplanets,” has met more and more success as astronomers devised techniques and took advantage of technological advances. The search dramatically accelerated in 2009 when NASA launched the Kepler Space Telescope, designed to find Earth-like planets elsewhere in the galaxy.

Though Kepler has focused on a relatively small patch of sky — as big up close as one’s hand extended at arm’s length — it has already returned a dazzling number of planet candidates, 2,326 so far. Those candidates are being investigated further to determine if they are indeed planets, with 35 confirmed so far. Scientists using a different technique from Kepler recently said that planets orbiting stars appears to be the rule rather than the exception in the galaxy, where they estimated there are one or more planets per star. With 200 billion to 400 billion stars, that estimate, if correct, would mean a staggering number of planets to explore.

“I don’t think we’ll have a paucity of planets. We’ll have more planets than we know what to do with,” Jayawardhana said. “You’re living through an incredibly exciting, revolutionary time.”

Jayawardhana said the findings so far show that the Milky Way is a surprisingly diverse place.

Already, planets have been found of many sizes, from giants larger than the solar system’s Jupiter to planets as small as Mars, at the edge of current detection abilities. One system has six giant planets, Jayawardhana said, with five jammed into orbits that would fit inside that of Mercury, the solar system planet closest to the sun. Planets have been found orbiting one partner of a stellar pair, called binary stars. And one binary system has been found where the planet orbits both stars.

Jayawardhana, who recently released the book “Strange New Worlds: The Search for Alien Planets and Life Beyond our Solar System,” spoke at the Harvard Museum of Natural History. He described two main methods for finding planets. In one, astronomers look for a wobble in a star’s rotation, which indicates that the mass of a planet is tugging on the star as it turns. Because the amount of wobble is dependent on a planet’s mass, scientists learn more than just a planet’s presence or absence.

A second technique examines a star’s light for periodic dimming, which is evidence of planets passing in front. This technique, employed by the Kepler Space Telescope, provides evidence of a planet’s size, since a larger planet will dim starlight more than a smaller one will. By combining the two techniques, Jayawardhana said, scientists can combine mass and size to understand a planet’s density, providing a clue as to whether the planet is rocky, like Earth, or made up of gas, like Jupiter.

In addition, scientists are now able to get clues about the atmosphere of planets that transit stars by examining a star’s light both before and after a planet passes in front of it. Because chemicals in the planet’s atmosphere absorb different wavelengths of light, by subtracting normal starlight from that, scientists can see the signature of the chemicals in the planetary atmosphere.

Other information that can be gleaned is how far a planet is from its star, an important factor in the search for life. Each star has a “habitable zone” where it is not too hot or too cold for life to emerge, scientists believe. Kepler’s mission is to find Earth-like planets in that habitable zone.

Scientists searching for life will look at the atmosphere of exoplanets for chemicals associated with life on Earth, including oxygen, methane, carbon dioxide, and water vapor.

But Jayawardhana cautioned against taking too narrow a view of the characteristics of life on other planets. If the search for exoplanets has taught us anything, he said, it’s to be prepared for surprises and to cast a wide net when it comes to looking for life. With the rapid increase in stellar discoveries, scientists will be able to do that through statistical techniques by analyzing the characteristics of large numbers of planets for signals that, though they don’t indicate Earth-like life, look unusual for a particular planet type. Those could lead to a new understanding of life in the galaxy.

“It’s only one example we have of life. To generalize is risky,” Jayawardhana said. “We do have to keep our minds open for completely different evidence of life.”

As described in the Proceedings of the National Academy of Sciences last month, the findings suggest that while people who share similar interests in music and movies are more likely to befriend one another, few interests are likely to spread among friends. It’s a result that challenges earlier research, which found that a host of social problems, from obesity to smoking to loneliness, quickly spread across social networks.

“The idea that ‘birds of a feather flock together’ is something we’ve known about for a long time,” said Kevin Lewis, a Ph.D. candidate in sociology who co-authored the paper with independent scholar Jason Kaufman and sociology graduate student Marco Gonzalez. “It’s not terribly surprising that, if you and I like the same things, we might become friends.

“What we’ve been able to show, however, is that this phenomenon is not actually as widespread as we once thought,” Lewis added. “There are only certain types of tastes that breed a connection. We’re also finding that this very common notion that what your friends do and like rubs off on you is not very widespread at all. We are not suggesting, of course, that taste in movies or music necessarily operates in the same way that obesity or depression does; but this paradigm that ‘everything spreads’ — it’s simply not true.”

The researchers gathered information from the profiles of students at an anonymous college. Once a year for four years, the researchers took snapshots of students’ profiles, recording their friends and what kinds of music, movies, and books they liked. That information was then broken down further, into genrelike “clusters” representing broad areas of interest that might diffuse throughout a network of friends.

Armed with that data, researchers used a computer program to evaluate how students’ friendship networks and preferences evolved over time, and to model the possible causes behind the changes.

“We used a simulation-based approach,” Lewis said. “So if we have a snapshot taken at two different times, the model examines all the possible trajectories that could have led from one point to another and identifies which is most likely.”

Importantly, Lewis added, the model controlled for a variety of possible causes for why two people might become friends or reasons why someone’s tastes might change over time, ensuring that researchers weren’t misdiagnosing the causes of those changes.

In the case of music, the results showed that people who listen to classical or jazz music are likely to be friends. The same was true for fans of light and classic rock. When it comes to onscreen entertainment, fans of raunchy comedies and gory movies are likely to be friends, as well as fans of darkly satirical films. Surprisingly, Lewis said, there was no connection between book preferences and friendship.

Only one type of taste — an interest in classical or jazz music — was found to spread across friendship networks, Lewis said.

“It’s not often you find a non-finding to be important, but I think this finding absolutely is important,” Lewis said. “There is a tendency to believe in peer influence — we all believe that what our friends like rubs off on us because it’s very easy to think of examples when that has happened. But we don’t remember the myriad instances that it doesn’t happen.”

“Much of Facebook’s business model is based on the assumption that Facebook users ‘influence’ one another through displays of things they ‘like’,” said Kaufman. “If you say you like a band, product, movie, etc., Facebook purports an ‘influence’ effect whereby your friends become more likely to adopt that preference in turn.

“What we found is that only in very specific instances does anything like ‘influence’ occur,” he continued. “This stands in contrast to an active research literature on the ‘contagiousness’ of various behaviors, such as obesity, smoking, and happiness, and gives pause at the millions, if not billions, of dollars spent every year on so-called ‘social media’ advertising campaigns.”

The finding is the result of a yearlong effort by a team of researchers led by Naoshige Uchida, associate professor of molecular and cellular biology, to examine a brain process known as reward prediction error. Thought to be a key component of learning, prediction error has long been considered the product of dopamine neurons firing in response to an unexpected “reward,” thus reinforcing the behavior that led to the reward.

But Uchida and colleagues from Harvard and Beth Israel Deaconess Medical Center report in the Jan. 18 issue of Nature that reward prediction error is actually the product of a complex interplay between two classes of neurons — one that relies on dopamine and an inhibitory class of neurons that uses the neurotransmitter GABA.

“Until now, no one knew how these GABA neurons were involved in the reward and punishment cycle,” Uchida said. “What we believe is happening is that they are inhibiting the dopamine neurons, so the two are working together to make the reward error computation.”

Before Uchida and his team could prove that GABA neurons were involved in the computation, however, they had to be sure what type of cells they were observing.

The challenge in studying both dopamine and GABA neurons is that the two cell types are intermingled in a relatively small area of the brain, making it difficult for researchers to definitively know which type they are observing. Ultimately, researchers developed an elegant solution to the problem.

Researchers genetically altered the neurons in two groups of mice — one for the dopamine neurons, the other for GABA neurons — to fire when hit by a pulse of laser light. Once researchers were certain they were measuring the correct type of neuron, they used electrodes to measure whether and when the neurons fired in response to expected and actual rewards.

The results, Uchida said, showed that while firing of dopamine neurons signaled reward prediction error, firing of GABA neurons signaled an expected reward. Taken together, GABA neurons help dopamine neurons calculate reward prediction error.

The finding is particularly important, Uchida said, because it sheds new light on how behaviors can be reinforced, either through normal brain function, or by damaging the way the two types of neurons interact.

“What happens with drug abuse is that many drugs, such as opioids and cannabinoids, target the GABA neurons,” he said. “What we are hypothesizing is that, by inhibiting those GABA neurons, you can lose this feedback cycle, so you keep getting reinforcing signals from the dopamine neurons.

“This is a new way of thinking about addiction in general,” Uchida continued. “Based on this theory, I believe you may be able to develop new theories or treatments for addiction.”

Funding for the research was provided by the Howard Hughes Medical Institute, the Human Frontier Science Program, the Richard and Susan Smith Family Foundation, the Alfred P. Sloan Foundation, and the Milton Fund.

Developed by Harvard’s Center for Geographic Analysis, WorldMap allows scholars to share access to view and edit geospatial information. Unlike similar tools, WorldMap allows the use of large, detailed datasets, and supports a number of formats.

First released in beta last July, the software already boasts 1,250 users from more than 100 countries. Users have contributed more than 1,700 mapping layers and created more than 500 map collections to support their research.

The bulk of the best geographic data resides outside any single institution. WorldMap takes a unique approach to this challenge by providing the global community with a platform to meet its needs. By so doing, the system increases the amount of high-quality spatial data in the public sphere.

WorldMap allows scholars to integrate information from diverse sources by making it possible to overlay data in users’ own computers with materials on the Web. The system also lets users incorporate paper maps, perform online digitizing, and link locations to other media.

The system allows for collaborations that can range from small groups in which all participants have editorial rights to interactive publications for large audiences. The system is also designed to support the research process, by allowing information to initially be made private, before being opened to larger groups for refinement, and finally to be published or released to the public.

Free and open to the public, WorldMap is cloud-hosted as well as open source, meaning new functions can be added to the system. A handful of new features are under development, including the ability to visualize change over time, searching place names for current and historic locations, and creating and editing online map layers.

One approach to treating cancer targets angiogenesis, or blood vessel growth. In this new investigation, senior author Raghu Kalluri, chief of the Division of Matrix Biology at Beth Israel Deaconess Medical Center (BIDMC) and professor of medicine at Harvard Medical School (HMS), wanted to find out if targeting a specific cell type, the pericyte, could inhibit tumor growth in the same way that other antiangiogenic drugs do. Pericytes are an important part of tissue vasculature, covering blood vessels and supporting their growth.

“If you just looked at tumor growth, the results were good,” says senior author Raghu Kalluri, chief of the Division of Matrix Biology at Beth Israel Deaconess Medical Center. “But when you looked at the whole picture, inhibiting tumor vessels was not controlling cancer progression. The cancer was, in fact, spreading.” Courtesy of BIDMC

Kalluri and his colleagues began by creating mice genetically engineered to support drug-induced depletion of pericytes in growing tumors. They then deleted pericytes in implanted mouse breast cancer tumors, decreasing pericyte numbers by 60 percent. The researchers saw a 30 percent decrease in tumor volumes in the deleted pericyte tumors compared with wild-type controls over 25 days. However, contrary to conventional clinical wisdom, the investigators found that the number of secondary lung tumors in the engineered mice had increased threefold compared with the control mice, indicating that the tumors had metastasized.

“If you just looked at tumor growth, the results were good,” says Kalluri. “But when you looked at the whole picture, inhibiting tumor vessels was not controlling cancer progression. The cancer was, in fact, spreading.”

To understand the mechanism behind this increased metastasis, Kalluri and his team examined the tumor’s microenvironment to find out what changes were taking place at the molecular level. They found a fivefold percentage increase in hypoxic areas in tumors lacking pericytes. “This suggested to us that without supportive pericytes, the vasculature inside the tumor was becoming weak and leaky — even more so than it already is inside most tumors — and this was reducing the flow of oxygen to the tumor,” explains Kalluri.

“Cancer cells respond to hypoxia by launching genetic survival programs,” he adds. To that end, the investigators found evidence of epithelial-to-mesenchymal transition (EMT), a change that makes the cells more mobile, so they can travel through those leaky vessels to new locations, and makes them behave more like stem cells, so they are better able to survive. Experiments that demonstrated fivefold increases in protein markers of EMT showed that the cells had undergone the change. The team also found a fivefold increase in activation of Met, a receptor molecule that promotes cell migration and growth.

Importantly, the team found that these molecular changes occurred inside the smaller, pericyte-depleted tumors that had increased incidences of secondary tumors in the lungs in the mouse models. “This suggested that smaller tumors are shedding more cancer cells into the blood and causing more metastasis,” says Kalluri. “We showed that a big tumor with good pericyte coverage is less metastatic than a smaller tumor of the same type with less pericyte coverage.”

Because cancer therapies such as Imatinib, Sunitinib, and others have been shown to decrease pericytes in tumors, the researchers’ next step was to perform the same experiments in mice with primary tumors, only this time, using Imatinib and Sunitinib rather than genetic programs to decrease pericyte numbers. And while both Imatinib and Sunitinib caused a 70 percent pericyte depletion, the end results stayed the same: metastasis increased threefold. “We showed that a big tumor with good pericyte coverage is less metastatic than a smaller tumor of the same type with less pericyte coverage,” says Kalluri, who corroborated these findings in multiple types of cancer by repeating these same experiments with implanted renal cell carcinoma and melanoma tumors.

Additional experiments showed that combining pericyte-depleting drugs with the Met-inhibiting drug helped suppress EMT and metastasis.

Finally, to determine whether the findings were relevant to patients, the scientists examined 130 breast cancer tumor samples of varying cancer stages and tumor sizes and compared pericyte levels with prognosis. They found that samples with low numbers of pericytes in tumor vasculature and high levels of Met expression correlated with the most deeply invasive cancers, distant metastasis, and five- and 10- year survival rates lower than 20 percent.

“These results are quite provocative and will influence clinical programs designed to target tumor angiogenesis,” says Ronald A. DePinho, president of the University of Texas MD Anderson Cancer Center. “These impressive studies will inform and refine potential therapeutic approaches for many cancers.”

Meanwhile, for Kalluri, the work suggests that certain assumptions about cancer must be revisited. “We must go back and audit the tumor and find out which cells play a protective role versus which cells promote growth and aggression,” says Kalluri. “Not everything is black and white. There are some cells inside a tumor that are actually good in certain contexts.”

To combat this “low fat is best” myth, nutrition experts at HSPH and chefs and dietitians at the Culinary Institute of America have developed five muffin recipes that incorporate healthy fats and whole grains, and use a lighter hand on the salt and sugar. The goal? To make over the ubiquitous low-fat muffin, touted as a “better-for-you” choice when in fact low-fat muffins often have reduced amounts of heart-healthy fats, such as liquid plant oils, but plenty of harmful carbohydrates in the form of white flour and sugar.

Other low-fat processed foods are not much better, and are often higher in sugar, carbohydrates, or salt than their full-fat counterparts. For good health, type of fat matters more than amount. Diets high in heavily processed carbohydrates can lead to weight gain and a rise in diabetes and heart disease risk.

“It’s time to end the low-fat myth,” said Walter Willett, professor of epidemiology and nutrition and chair of the Department of Nutrition at HSPH. “Unfortunately, many well-motivated people have been led to believe that all fats are bad and that foods loaded with white flour and sugar are healthy choices. This has clearly contributed to the epidemic of diabetes we are experiencing and to premature death for many.”

A regular blueberry muffin from a national coffee shop chain has 450 calories on average. Most of those come from carbohydrates, primarily white flour and sugar. However, now that national chains have eliminated trans fats, a regular muffin does have heart-healthy fat, usually from soybean or canola oil. A low-fat muffin has about the same amount of calories, but contains more carbohydrates and sugar — and about 60 percent more sodium (700 milligrams) — than a regular muffin.

The new blueberry muffin recipe offered by HSPH and the Culinary Institute of America is less than half the size of a coffee shop muffin and has just 130 calories. It is made with a mixture of whole wheat, white, and almond flour and uses canola oil, a healthy fat.

“These five recipes not only include a wide variety of whole grain and nut flours, they also demonstrate how more unusual ingredients like canned chickpeas and extra virgin olive oil can be used in baking,” says Richard Coppedge Jr., chef-instructor at the Culinary Institute and a certified master baker.

The Culinary Institute and HSPH offer a dozen healthy baking tips that chefs and home cooks can use to build a healthier muffin. Here are a few of their tips:

Downsize portions. The megamuffins popular in shops are two to three times the size of the muffins your grandmother might have baked.

Go whole on the grains. It’s easy to substitute whole wheat flour for 50 percent of the white flour in recipes without harming taste or texture. And with a few recipe alterations, delicious muffins can be made with 100 percent whole grains. See the lemon chickpea breakfast muffin and the whole wheat banana nut muffin recipes as examples.

Slash the sugar. You can cut 25 percent of the sugar from most standard muffin recipes without a negative impact on flavor or texture.

Pour on the oil. Liquid plant oils — canola, extra virgin olive oil, corn, sunflower — help keep whole grain muffins moist and are a healthier choice than butter or shortening.

Bring out the nuts. For extra protein and an additional source of healthy fats, add chopped nuts.

Scale back salt. The best way to reduce salt is to make a smaller muffin and to pair muffins with foods, such as vegetables and fruits, that are sodium-free.

Pump up the produce — and flavor. Fresh whole fruit and unsweetened dried fruit naturally contain sugar, but unlike other sweeteners, they also contain fiber and important nutrients. Using fruit in your muffins allows for a lighter hand on the added sugar. Vegetables and spices can add interesting textures and savory flavors to muffins.

See recipes for blueberry muffins, cranberry orange muffins, jalapeño cheddar corn muffins, lemon chickpea breakfast muffins, and whole wheat banana nut muffins here.

The approach was found to increase drug efficacy by 200-fold in in vitro studies based on the ability of these nanomaterials to both protect the drug from degradation and concentrate it at key target sites, such as regions of the pancreas that contain the insulin-producing cells. The dramatic increase in efficacy also means that much smaller amounts of drugs would be needed for treatment, opening the possibility of significantly reduced toxic side effects, as well as lower treatment costs.

The research was led by Wyss Institute founding director Donald Ingber and Kaustabh Ghosh, a former postdoctoral fellow at Harvard-affiliated Children’s Hospital Boston. Their findings appear the current issue of Nano Letters.

“The consequences of type 1 diabetes are felt [both in] the people who live with the disease and in the terrible strain that treatment costs put on the economy,” said Ingber.  “In keeping with our vision at the Wyss Institute, we hope that the programmable nanotherapy we have developed here will have a major positive impact on people’s lives in the future.”

Type 1 diabetes, which often strikes children and young adults, is a debilitating disease in which the body’s immune system progressively destroys the cells in the pancreas that produce insulin. According to the Juvenile Diabetes Research Foundation, as many as 3 million Americans have the disease and some 30,000 new cases are diagnosed every year.

The risk of developing type 1 diabetes, which can lead to serious health complications such as kidney failure and blindness, can be predicted with 90 percent accuracy. But therapeutic intervention for people identified as high risk has been limited because many systemic treatments are barred from clinical use due to the severe side effects they produce when used at the high doses required to achieve a therapeutic response.

Using nanoparticles that can be programmed to deliver drug or stem cell therapies to specific disease sites is an excellent alternative to systemic treatments because improved responses can be obtained with significantly lower therapeutic doses and hence, fewer side effects.  To date, such nanotherapeutics have been developed primarily to treat cancer, because they can home in on the tumor via its leaky blood vessels. The challenge has been to develop ways to selectively deliver drugs to treat other diseases in which the tissues of interest are not as easily targeted. The research team addressed this problem by using a unique homing peptide molecule to create “smart” nanoparticles that can seek out and bind to the capillary blood vessels in the islets of the pancreas that feed the insulin-producing cells most at risk during disease onset.

Ingber, who is the Judah Folkman Professor of Vascular Biology at Harvard Medical School and Children’s Hospital Boston, is also a professor of bioengineering at Harvard’s School of Engineering and Applied Sciences. Ghosh is now an assistant professor of bioengineering at the University of California, Riverside. Wyss Institute postdoctoral fellows Umai Kanapathipillai and Netanel Korin also contributed to the work, as did Jason McCarthy, assistant professor in radiology at Harvard Medical School and an assistant in chemistry at Harvard-affiliated Massachusetts General Hospital.

The research was supported by the Wyss Institute and a SysCODE (Systems-Based Consortium for Organ Design and Engineering) grant from the National Institutes of Health that supports a group of seven clinical and academic institutions working to develop new ways to induce regeneration of organs, including the pancreas.

A new study finds that participating in these races actually is associated with a relatively low risk of cardiac arrest, compared with other forms of athletics. An analysis of 10 years of data, appearing in the Jan. 12 New England Journal of Medicine, reveals that most of those experiencing cardiac arrest during marathons and half-marathons had undiagnosed, pre-existing cardiac abnormalities.  Male marathon participants accounted for most cardiac arrests and appear to be at increased risk. The study also identifies bystander-initiated cardiopulmonary resuscitation (CPR) as a key factor in patient survival.

“This study provides the first accurate, comprehensive characterization of cardiac arrest and sudden cardiac death risk in this population,” says Harvard Medical School Assistant Professor of Medicine Aaron Baggish, who is director of the Cardiovascular Performance Program in the Massachusetts General Hospital (MGH) division of cardiology and senior author of the study. ”The general consensus — based on intense media coverage of cardiac arrests that happen during these races — has been that the risk was very high.  But we found that the risk of cardiac arrest for marathon and half-marathon runners is equal to or less than the risk for other athletes — including triathletes, college athletes, and casual joggers.  This finding provides important reassurance that this is a generally safe and well-tolerated activity.”

The authors note that, while several studies have examined sudden cardiac deaths in young, competitive athletes, there had been no comprehensive study of marathon participants, who are often older and may have unknown underlying medical conditions.  They prospectively compiled a database of cardiac arrest cases occurring during or at the finish lines of all U.S. marathons and half-marathons from 2000 until mid-2010.  Letters were sent to survivors of each cardiac event — or to the next of kin for cardiac deaths — requesting their participation in the study.  Those agreeing to participate completed an extensive interview process examining demographic data, personal and family medical history, cardiac risk factors or previous diagnoses, and information about the cardiac event. Complete medical records, including post-cardiac arrest testing and autopsy data, were collected and analyzed whenever possible.

Out of almost 11 million registered participants in the races documented during the study period, the research team identified 59 cardiac arrests — 40 at marathons and 19 at half-marathons.  More than 85 percent of the cardiac arrests took place in men. While the overall incidence of cardiac arrests during the study period was stable, the risk among male marathon runners rose significantly over time.  Of the 59 cardiac arrests, 42 were fatal. This 71 percent mortality is markedly better than the usual 92 percent rate for out-of-hospital arrests, probably because of the presence of spectators and on-site medical services that facilitate rapid response, the authors note.

Among the 31 affected runners for whom detailed medical information was available, 23 had died — 15 of whom had definite or probable hypertrophic cardiomyopathy.  This abnormal thickening of the heart muscle is the most common cause of sudden cardiac death in young athletes but previously has not been considered an issue in the older running population. Nine of those who died had additional cardiac abnormalities. Among cardiac arrest survivors, underlying coronary artery disease was the dominant pathology, but no participants with coronary disease had any evidence of acute coronary plaque rupture.  Factors most strongly associated with survival were rapid initiation of CPR by bystanders witnessing the event and a diagnosis other than hypertrophic cardiomyopathy.

“The lack of plaque rupture — a critical event in many heart attacks — was an intriguing and surprising finding,” Baggish says.  “It suggests that the kind of underlying disease that causes cardiac arrest in distance runners may be detectable by a simple stress test prior to race day.  Our next steps are to investigate strategies for pre-race runner education and heart disease screening and to study the contribution of specific risk factors in more detail.  A big take-home message of the study is the importance of bystander CPR, which is a relatively simple skill that can be learned by everyone in the community.  Recognition of this important finding calls us all to action, and we will be offering the first-ever CPR education session for runners, family members, and spectators at this year’s Boston Marathon.”

Bruce Spiegelman, a cell biologist at Dana-Farber, is senior author of the report, posted as an advance online publication by the journal Nature. The first author is Pontus Bostrom, a postdoctoral fellow in the Spiegelman lab.

“It’s exciting to find a natural substance connected to exercise that has such clear therapeutic potential,” said Bostrom.

Spiegelman dubbed the hormone “irisin,” after Iris, a Greek messenger goddess. He said the discovery is an important first step in understanding the biological mechanisms that translate physical exercise into beneficial changes throughout the body, both in healthy people and in preventing or treating disease.

“There has been a feeling in the field that exercise ‘talks to’ various tissues in the body,” said Spiegelman, a professor of cell biology at Harvard Medical School. “But the question has been, how?”

According to the report, the irisin hormone has direct and “powerful effects” on adipose, or fatty, tissue — subcutaneous deposits of white fat that store excess calories and that contribute to obesity.

When irisin levels rise through exercise — or, in this study, when irisin was injected into mice — the hormone switches on genes that convert white fat into “good” brown fat. This is beneficial because brown fat burns off more excess calories than does exercise alone.

Only a small amount of brown fat is found in adults, but infants have more — an evolutionary echo of how mammals keep themselves warm while hibernating. In the wake of findings by Spiegelman and others, there has been a surge of interest in the therapeutic possibilities of increasing brown fat in adults.

Along with stimulating brown fat development, irisin was shown to improve glucose tolerance, a key measure of metabolic health, in mice fed a high-fat diet.

The discovery won’t allow people to skip the gym and build muscles by taking irisin supplements, Spiegelman cautioned, because the hormone doesn’t appear to make muscles stronger. Experiments showed that irisin levels increase as a result of repeated bouts of prolonged exercise, but not during short-term muscle activity.

The Dana-Farber team identified irisin in a search for genes and proteins regulated by a master metabolic regulator, called PGC1-alpha, which is turned on by exercise. Spiegelman’s group had discovered PGC1-alpha in previous research.

Bostrom said the hunt for molecular targets of increased PGC1-alpha activity ultimately pinpointed irisin, which turned out to be located within the outer membrane of muscle cells. This discovery ran counter to other scientists’ contentions that such a protein would reside in the cell’s nucleus.

To test whether increasing irisin alone could mimic exercise benefits, the scientists injected modest amounts into sedentary mice that were obese and pre-diabetic.

With 10 days of treatment, the mice had better control of blood sugar and insulin levels — in effect, preventing the onset of diabetes — and lost a small amount of weight. Although the weight loss was small, Spiegelman said that the hormone may have a greater effect when given for longer periods.

There were no signs of toxicity or side effects, a finding that was predicted because the researchers limited the increase of irisin to levels typically caused by exercise.

In part because it is a natural substance and because the mouse and human forms of the protein are identical, Spiegelman said it should be possible to move an irisin-based drug rapidly into clinical testing — perhaps within two years.

The irisin discovery has been licensed by Dana-Farber exclusively to Ember Therapeutics for drug development. Ember is a Boston-based startup co-founded by Spiegelman and scientists at the Harvard-affiliated Joslin Diabetes Center and the Scripps Research Institute in Florida.

The scientists said their findings merely scratch the surface of irisin’s multiple effects. They are continuing to explore the hormone’s possible benefits in metabolic diseases like diabetes, insulin resistance, and obesity, which constitute a growing epidemic around the world, as well as neurodegenerative illnesses such as Parkinson’s disease.

Spiegelman added that as growing evidence implicates obesity and physical inactivity in cancer development, it’s conceivable irisin-based drugs may have value in prevention and treatment of the disease.

Other authors, in addition to Spiegelman and Bostrom, are from Dana-Farber; Harvard Medical School; Harvard affiliated Brigham and Women’s Hospital; University of California, San Francisco; Universita Politecnica delle Marche, Ancona, Italy; Odense University Hospital, Denmark; and LakePharma, Belmont, Calif.

The National Institutes of Health funded the research.

As described in a paper recently published in the journal Nature, Harvard Professor of Earth and Planetary Sciences Peter Huybers confirmed that slow changes in both the tilt and orientation of Earth’s spin axis combined to help determine when the major deglaciations of the past million years occurred.

“These periods of deglaciation saw massive climate changes,” Huybers said. “Sea level increased by 130 meters, temperatures rose by about 5 degrees C, and atmospheric CO2 went from 180 to 280 parts per million. We ought to understand what caused these massive changes in past climate if we are to predict long-term changes in future climate with any confidence. And at least now we know with greater than 99 percent confidence that the interaction between obliquity and precession are among the factors that contribute to deglaciation.”

In this context, obliquity refers to the tilt of the spin axis relative to the plane of Earth’s orbit, and precession refers to changes in the direction that the spin axis points, relative to Earth’s elongated, or eccentric, orbit.

While Huybers’ research is the first to prove a connection between obliquity, precession, and deglaciations, suggestions that the Earth’s orbit plays a role in the formation or loss of glaciers are nothing new.

By the early 1840s, just a few years after the notion of the Ice Age was first articulated by geologist and later Harvard Professor Louis Agassiz, scientists began proposing that orbital changes were behind periods of glaciation. In the intervening 170 years, Huybers said, dozens of additional hypotheses have been presented, but it has been difficult to distinguish between these many competing models.

“We don’t understand why glacial cycles have occurred, not for lack of ideas, but rather because we lack means to rule the wrong ideas out,” Huybers said.  “A lot of people have tried to tie when ice ages started or ended to variations in the orbital cycle, but this is difficult because we don’t know exactly when ice ages occurred in the past.

“Our uncertainty in when deglaciations occurred averages plus or minus 10,000 years during the last million years, and this uncertainty encompasses an entire cycle of precession. Not knowing what the orbital configuration was makes it difficult to test whether any particular orbital configuration influences deglaciation.”

Though it has previously been shown that obliquity — with its longer, roughly 40,000-year cycle — is related to deglaciations, Huybers said, the innovation here was to test for whether obliquity and precession are together related to worldwide glacier loss.

To deal with the uncertainty in the geological records, Huybers developed a methodology through tinkering with “synthetic” records. Essentially, he constructed random realization of glacial cycles to which he added distortions — such as errors in timing and noise in observations — similar to those found in geologic data. Using this synthetic data, he experimented with many techniques until hitting upon one that worked, which he then applied to the actual data, showing the relationship between orbital cycles and deglaciations.

“The pattern that emerges is the following: At the same time we’re seeing high obliquity, we also tend to get an alignment with precession whenever deglaciation occurs,” Huybers said. “When you get that alignment, the radiation that the Northern Hemisphere receives during summer increases by tens of watts per meter squared, and if large Northern ice sheets are present, they tend to disintegrate. These statistical findings agree exactly with what Milutin Milankovitch, a Serbian geophysicist, proposed in the first half of the 20th century.”

Though his work suggests that orbital configuration contributes to the loss of glacial ice, Huybers was quick to emphasize that it is only one factor among many.

“It could also be that orbital forcing causes a rise is atmospheric CO2, and that it’s the increased CO2 that drives the loss of ice sheets,” he said. “In all likelihood, both CO2 and increased summer radiation contribute to deglaciation. They’re both expected to push the climate system toward less ice.

“Another important aspect to consider is that the orbital configuration we now have is almost exactly where it was 20,000 years ago, during the Last Glacial Maximum, but this time we’re near a glacial minimum,” he said. “If you think about what the difference is between then and now, it’s not the orbital configuration, it’s the CO2. I think that’s important to keep in mind, because it shows that glacial changes are not a simple function of the orbital configuration.”

But researchers, led by Harvard Medical School Assistant Professor of Cell Biology Samara Reck-Peterson, believe dynein’s theatrical strut and apparent inefficiency may help keep cells alive and healthy.

These findings appear online Jan. 8 in Nature Structural & Molecular Biology.

Molecular motors, built from proteins, are a kind of transport service that keep cells functioning. They traffic essential chemical packages between the heart of the cell, the nucleus, and the cell periphery. In elongated cells such as neurons, this can be a big commute in cellular miles, equivalent to a person walking from Boston to Manhattan. The constant shuttling of materials by motors keeps cells alive and allows cells to move and divide, and talk to their neighbors.

It’s no surprise, then, that when these motors stop functioning, serious problems can result. In fact, defects in dynein-based transport have been linked to Lou Gehrig’s and Parkinson’s disease and the neurodevelopmental disease lissencephaly.

To understand how this essential protein machine works, Reck-Peterson and colleagues decided to study the dynamics of motor movement on the nanoscale by developing protein engineering methods and then implementing single molecule imaging technologies.

First, they purified dynein motors, whose “legs” were tagged with fluorescent markers, and microtubules, long filaments that serve as dynein’s highway. Next, they put these components on a microscope slide and directly visualized dynein motors stepping along microtubule tracks.

“Dynein is critical for the function of every cell in our bodies,” said Reck-Peterson. “Deciphering the walking mechanism of this and other tiny machines may one day shed light on the molecular origins of certain diseases.”

This research was funded by the Rita Allen Foundation, the American Heart Association, the Armenise-Harvard Foundation, and a National Institutes of Health Director’s New Innovator Award. Harvard affiliated co-authors included Weihong Qiu, Nathan Derr, Brian Goodman, and William Shih.

The study appears Jan. 9 in an online edition of Tobacco Control and will appear in a later print issue.

“What this study shows is the need for the Food and Drug Administration, which oversees regulation of both medications to help smokers quit and tobacco products, to approve only medications that have been proven to be effective in helping smokers quit in the long term and to lower nicotine in order to reduce the addictiveness of cigarettes,” said co-author Gregory Connolly, director of the Center for Global Tobacco Control at HSPH.

In the prospective cohort study, the researchers, including lead author Hillel Alpert, research scientist at HSPH, and co-author Lois Biener of the University of Massachusetts Boston’s Center for Survey Research, followed 787 adult smokers in Massachusetts who had recently quit smoking. The participants were surveyed over three time periods: 2001-2002, 2003-2004, and 2005-2006. Participants were asked whether they had used a nicotine replacement therapy in the form of the nicotine patch (placed on the skin), nicotine gum, nicotine inhaler, or nasal spray to help them quit, and if so, what was the longest period of time they had used the product continuously. They also were asked if they had joined a quit-smoking program or received help from a doctor, counselor, or other professional.

The results showed that, for each time period, almost one-third of recent quitters reported to have relapsed. The researchers found no difference in relapse rate among those who used NRT for more than six weeks, with or without professional counseling. No difference in quitting success with use of NRT was found for either heavy or light smokers.

“This study shows that using NRT is no more effective in helping people stop smoking cigarettes in the long term than trying to quit on one’s own,” Alpert said. He added that even though clinical trials have found NRT to be effective, the new findings demonstrate the importance of empirical studies regarding effectiveness when used in the general population.

Biener said that using public funds to provide NRT to the population at large is of questionable value, particularly when it reduces the amount of money available for smoking interventions shown in previous studies to be effective, such as media campaigns, promotion of no-smoking policies, and tobacco price increases.

Smoking cessation medications have been available over the counter since 1996, yet U.S. Centers for Disease Control and Prevention statistics show that the previous adult smoking rate decline and quitting rates have stalled in the past five years.

Funding for the study was provided by the National Cancer Institute, State and Community Tobacco Control Interventions Research Grant Program.

The researchers, co-led by Associate Professor Amy Wagers of Harvard’s Department of Stem Cell and Regenerative Biology and the Harvard Stem Cell Institute, has found that impairment of the body’s ability to replace protective myelin sheaths, which surround nerve fibers and allow them to send signals properly, may be reversible, offering new hope that therapeutic strategies aimed at restoring efficient regeneration can be effective in the central nervous system throughout life.

In a proof-of-principle study published in the journal Cell Stem Cell, the researchers report that defects in the regeneration of the myelin sheaths surrounding nerves, which are lost in diseases such as MS, may be at least partially corrected after exposing an old animal to the circulatory system of a young animal. Myelin is a fatty substance that protects nerves and aids in the quick transmission of signals between nerve cells.

Using a surgical technique, the researchers introduced an experimental demyelinating injury in the spinal cord of an old mouse, creating small areas of myelin loss, and then exposed those areas to cells found in the blood of a young mouse. By doing so, they found that the influx of certain immune cells, called macrophages, from the young mouse helped resident stem cells restore effective remyelination in the old mouse’s spinal cord. This rejuvenating effect of young immune cells was aided in part by the greater efficiency of the young cells in clearing away myelin debris created by the demyelinating injury. Prior studies have shown that this debris impedes the regeneration of myelin.

“Aging impairs regenerative potential in the central nervous system,” said Wagers, who is based at the Joslin Diabetes Center, and who co-led the study with Professor Robin Franklin, director of the MS Society’s Cambridge Centre for Myelin Repair at the University of Cambridge. “This impairment can be reversed, however, suggesting that the eventual development of cell-based or drug-based interventions that mimic the rejuvenation signals found in our study could be used therapeutically.”

This could be particularly useful, she said, in treating MS, which typically spans many decades of life, and thus is likely to be influenced by age-dependent reductions in the ability of myelin to regenerate. In MS, the body’s own immune system attacks the myelin sheath and prevents nerve fibers in the brain from sending signals properly, which can cause mild symptoms such as limb numbness or more serious ones like losing the ability to walk or speak. As people with MS age, remyelination decreases significantly, eventually causing permanent loss of nerve fibers.

“For MS sufferers,” said Franklin, “this means that, in theory, regenerative therapies will work throughout the duration of the disease. Specifically, it means that remyelination therapies do not need to be based on stem cell transplantation, since the stem cells already present in the brain and spinal cord can be made to regenerate myelin, regardless of a person’s age.”

Other Harvard co-authors of the study were Tata Nageswara Rao and Jennifer L. Shadrach of Wagers’ lab.

As described in Nature Nanotechnology on Dec. 11, a research team led by Charles Lieber, the Mark Hyman Jr. Professor of Chemistry, have succeeded for the first time in creating an integrated nanopore detector, a development that opens the door to the creation of devices that could use arrays of millions of the microscopic holes to sequence DNA quickly and cheaply.

First described more than 15 years ago, nanopore sequencing measures subtle electrical current changes produced as the four base molecules that make up DNA pass through the pore. By reading those changes, researchers can effectively sequence DNA.

But reading those subtle changes in current is far from easy. A series of challenges — from how to record the tiny changes in current to how to scale up the sequencing process — meant the process has never been possible on a large scale. Lieber and his team, however, believe they have found a unified solution to most of those problems.

“Until we developed our detector, there was no way to locally measure the changes in current,” Lieber said. “Our method is ideal because it is extremely localized. We can use all the existing work that has been done on nanopores, but with a local detector we’re one step closer to completely revolutionizing sequencing.”

The detector developed by Lieber and his team grew out of earlier work on nanowires. Using the ultra-thin wires as a nanoscale transistor, they are able to measure the changes in current more locally and accurately than ever before.

“The nanowire transistor measures the electrical potential change at the pore and effectively amplifies the signal,” Lieber said. “In addition to a larger signal, that allows us to read things much more quickly. That’s important because DNA is so large [that] the throughput for any sequencing method needs to be high. In principle, this detector can work at gigahertz frequencies.”

“The nanowire transistor measures the electrical potential change at the pore and effectively amplifies the signal,” said Charles Lieber. “In addition to a larger signal, that allows us to read things much more quickly." File photo Kris Snibbe/Harvard Staff Photographer

The highly localized measurement also opens the door to parallel sequencing, which uses arrays of millions of pores to speed the sequencing process dramatically.

In addition to the potential for greatly improving the speed of sequencing, the new detector holds the promise of dramatically reducing the cost of DNA sequencing, said Ping Xie, an associate of the Department of Chemistry and Chemical Biology and co-author of the paper describing the research.

Current sequencing methods often start with a process called the polymerase chain reaction, or DNA amplification, which copies a small amount of DNA thousands of millions of times, making it easier to sequence. Though critically important to biology, the process is expensive, requiring chemical supplies and expensive laboratory equipment.

In the future, Xie said, it will be possible to build the nanopore sequencing technology onto a silicon chip, allowing doctors, researchers, or even the average person to use DNA sequencing as a diagnostic tool.

The breakthrough by Lieber’s team could soon make the transition from lab to commercial product. The Harvard Office of Technology Development is working on a strategy to commercialize the technology appropriately, including licensing it to a company that plans to incorporate it into their DNA sequencing platform.

“Right now, we are limited in our ability to perform DNA sequencing,” Xie said. “Current sequencing technology is where computers were in the ’50s and ’60s. It requires a lot of equipment and is very expensive. But just 50 years later, computers are everywhere, even in greeting cards. Our detector opens the door to doing a blood draw and immediately knowing what a patient is infected with, and very quickly making treatment decisions.”

In the Pacific Islands, however, sailors have long claimed to have something else in their navigational toolbox, te lapa — loosely translated as “underwater lightning” — flashes of iridescent light that appear in nighttime waters, and which some claim point toward nearby islands.

But could  “underwater lightning” be real? And could the strange phenomenon have helped lead wayward sailors to safe harbors for thousands of years? Might it even have played a critical role in human migrations through the South Pacific by pointing ancient peoples toward islands just over the horizon?

John Huth thinks so, and he may have come up with an explanation of what would cause it.

Huth, the Donner Professor of Science and creator of the popular “Primitive Navigation” course, spent most of last summer investigating the mysterious lights. His experiments suggest that they may be the product of millions of single-celled microorganisms called dinoflagellates, which emit light when subjected to pressure waves like those caused by darting fish.

“Initially, my interest in this grew out of my navigation course,” Huth said. “Being a physicist, I couldn’t help but come up with ideas for what it might be. I wasn’t completely convinced it wasn’t some form of bioluminescence that wasn’t commonly known. But people who describe it say it’s quite different from the kind of phosphorescence that gets kicked up in the wake of canoes or in waves at the beach.”

Huth is not the first to attempt to search for a cause for the lights. First described in the late 1960s and early ’70s by anthropologist David Lewis in a book on the navigation strategies of Pacific Islanders, the lights were initially dismissed as fantasy when other researchers reported that they were unable to see them. Some critics, Huth said, thought that pursuing “underwater lightning” was akin to chasing the abominable snowman.

Undaunted, Huth decided to try to settle, once and for all, whether the phenomenon was real. Among his first stops was the lab of J. Woodland “Woody” Hastings, the Paul C. Mangelsdorf Research Professor of Natural Sciences and an authority on dinoflagellates and bioluminescence.

“He gave me the ‘cook’s tour,’ if you like, of dinoflagellates,” Huth said.

A type of plankton, dinoflagellates are tiny, single-celled organisms that live in seawater. During the day, they move closer to the surface, where they use the sun’s energy to photosynthesize. At night, the creatures sometimes emit small flashes of light that look like sparks. When subjected to a pressure wave, however, they can emit long flashes of light.

Hastings eventually gave Huth a “starter kit” — a small sample of seawater filled with thousands of the organisms, which he “grew” over the summer, eventually producing approximately three liters of water. To conduct his tests, Huth filled a long trough with the water, and drew a segmented fishing lure, designed to mimic the darting motion of fish, through it.

“Sure enough, it looked, at least to my eyes, like underwater lightning,” he said. “We were able to capture it on video and have sent the video to people in the Santa Cruz reef islands who claim to have seen it [firsthand] to see whether or not it looks like what they think of as underwater lightning. This is what you might call an existence proof, that darting fish can produce something that looks like the phenomenon people have reported.”

But proving that underwater lightning may exist is only the first step. Proving whether the lights are actually a useful navigational tool, Huth said, will take more work.

“The next step is to see it in the field,” he said. “From there, you can begin to ask important questions about whether it is directional, and if it is truly directional, what causes the directionality.”

Though it is far too early to say what may be behind the phenomenon, Huth’s colleagues have suggested possible avenues for investigation.

“At this point, we are completely in the realm of conjecture, but some have mentioned that there are migratory fish, and in particular eels,” Huth said. “It’s conceivable that there may be fish that migrate from island to island. One candidate is the large spotted moray eel. Unfortunately, not much is known about its habits, but we do know that it is found in areas where underwater lightning has been reported, and that it is nocturnal.”

Huth is also working to gather reports in an effort to determine how widespread the phenomenon might be. Though the lights are most commonly reported in the Pacific Islands, Huth has found a report from 1727 that suggests underwater lightning has been spotted off the coast of Brazil.

“If you look at the migration of humans in the Pacific Islands, it required some purposefulness. In many cases, they had to sail into the wind and against the current,” Huth said. “It’s possible that some combination of factors — migratory birds, accidental drift, and also underwater lightning — were used by early navigators.”

Described in the Dec. 20 issue of the journal Nature, the two planets, dubbed Kepler-20e and Kepler-20f, are the smallest planets found by the Kepler mission to date. They have diameters of 6,900 miles and 8,200 miles — equivalent to 0.87 times Earth (slightly smaller than Venus) and 1.03 times Earth. These worlds are expected to have rocky compositions, so their masses should be, respectively, approximately 1.7 and 3 times Earth’s.

“The goal of Kepler is to find Earth-sized planets in the habitable zone. Proving the existence of Earth-sized exoplanets is a major step toward achieving that goal,” said Francois Fressin, a research associate at the Harvard-Smithsonian Center for Astrophysics (CfA).

Both worlds circle Kepler-20, a star located 950 light-years from Earth. Though that star is slightly cooler than the Sun, the planets’ tight orbits — Kepler-20e orbits every 6.1 days at a distance of 4.7 million miles, while Kepler-20f orbits every 19.6 days at a distance of 10.3 million miles — they are heated to temperatures of 1,400 and 800 degrees Fahrenheit, respectively.

In addition to the two newfound worlds, the Kepler-20 system contains three previously identified planets. All five have orbits closer than Mercury in our solar system, and show an unexpected arrangement. In our solar system, small, rocky worlds orbit close to the Sun, while large, gas, giant ones orbit farther out. In contrast, the planets of Kepler-20 are organized in alternating size: big, little, big, little, big.

“We were surprised to find this system of flip-flopping planets,” said David Charbonneau, professor of astronomy and a co-author of the Nature paper. “It’s very different than our solar system.”

The three largest planets are designated Kepler-20b, Kepler-20c, and Kepler-20d. They have diameters of 15,000, 24,600, and 22,000 miles, and orbit once every 3.7, 10.9, and 77.6 days, respectively.

In the hunt for planets, Kepler identifies “objects of interest” by looking for stars that dim slightly, which can occur when a planet crosses the star’s face. Such dimming, however, could be caused by a variety of phenomena. To determine whether an object truly is a planet, astronomers use Blender, a software package developed by Fressin and Willie Torres of CfA. After running millions of possible simulations, the team concluded that the odds are strongly in favor of Kepler-20e and Kepler-20f being planets.

Fressin and Torres also used Blender to confirm the existence of Kepler-22b, a planet in the habitable zone of its star that was announced by NASA earlier this month. However, that world was much larger than Earth.

“These new planets are significantly smaller than anything found up till now orbiting a sunlike star,” added Fressin.

In a commentary in the Dec. 20 Annals of Internal Medicine, investigators from Harvard-affiliated Massachusetts General Hospital (MGH), the Schaeffer Center for Health Policy and Economics at the University of Southern California (USC), and The National Center on Addiction and Substance Abuse at Columbia University (CASA Columbia) describe the probable contribution of Internet pharmacies to the problem and outline potential strategies for addressing the problem.

“Controlled prescription drugs like Oxycontin, Xanax, and Ritalin are easily purchased over the Internet without a prescription, yet physician awareness of this problem is low,” says Anupam B. Jena of the MGH Department of Medicine, lead author of the article, and a clinical fellow in medicine at Harvard Medical School.  ”Abuse of medications purchased from websites can pose unique challenges to physicians because patients who abuse these medications may not fit clinical stereotypes of drug abusers.”

The authors note that abuse of controlled prescription drugs now exceeds abuse of all illegal drugs combined, except marijuana. Some illegitimate online pharmacies sell drugs with no prescription or medical information at all while others ask for completion of a questionnaire before a prescription is issued by a physician who has never seen the patient. Studies from CASA Columbia have found that 85 percent of websites offering controlled prescription drugs do not require a prescription, and many that do allow the prescription to be faxed, increasing the risk of forgery or fraud.

“The Internet serves as an open channel for distribution of controlled prescription drugs with no mechanisms to even block sales to children. This is particularly dangerous given that addiction is a disease that, in most cases, originates with substance use in adolescence,” says Susan Foster, vice president and director of Policy Research and Analysis at CASA Columbia.

Additional investigations by U.S. agencies have verified the ease with which controlled drugs can be purchased online, but little information is available on how drugs acquired that way are used.  While some surveys suggest that as many as 10 percent of prescription drug abusers obtain their drugs online, the authors stress that such surveys probably underestimate the situation and would not reach individuals most likely to abuse prescription drugs purchased over the Internet.  They also note that surveys in drug treatment centers would totally miss local drug dealers, who are increasingly likely to access their supplies online.

Earlier this year Jena and Dana Goldman, director of the Schaeffer Center at USC and also a co-author of the current article, published a study finding that the states with the greatest expansion in high-speed Internet access from 2000 to 2007 also had the largest increase in admissions for treatment of prescription drug abuse.  They estimated that for every 10 percent increase in high-speed Internet use during those years, admissions for prescription drug abuse increased 1 percent.  “Prescription use starts with the physician,” says Goldman, “and we need to more actively engage them to control illicit use.  Access to universal, electronic prescription records would be of great assistance in this regard.”

Both federal and private agencies have taken measures to reduce the impact of illicit Internet pharmacies, including the 2008 passage of the Ryan Haight Online Pharmacy Consumer Protection Act, which specifically prohibits delivery of controlled substances prescribed by a physician who had never examined the patient.  But the success of that law and related efforts, such as FDA warning letters to Internet pharmacies and their service providers, is unknown.  The authors note that regulatory efforts also are “stymied by these pharmacies’ ability to appear, disappear, and reappear constantly,” and the reluctance of search engines to stop running ads for rogue online pharmacies.  The increasing online availability of prescription drugs may entice individuals believed to be at low risk for drug abuse to overuse controlled medications.

The authors note that, while physicians and other health care providers should play a major part in addressing the challenges posed by Internet pharmacies, their awareness of the problem and ability to recognize and treat substance abuse of any kind is usually limited.  “Physicians need to educate patients about the risks of purchasing any medications over the Internet and should consider brief but routine questioning about Internet-based medication use,” says Jena, who is also a senior fellow at the Schaeffer Center at USC.  “Given the ability of illegal online pharmacies to evade law enforcement efforts, physician awareness and involvement will be crucial to reducing this problem.”

Robert Blendon, HSPH professor of health policy and political analysis, said that unlike European nations where citizens agree that health care should be part of their basic social contract, Americans are deeply divided over the issue, with many feeling that the federal government shouldn’t inject itself into the medical profession.

That helps explain why the federal government appeared so dysfunctional over the past two years, Blendon said. In that time, Americans got what they voted for, a Congress with members who arrived with a mandate to shrink domestic programs, and to avoid compromising with the president on complex issues, including health care reform.

“They were elected to cut spending and cut taxes, not play nice with the president,” Blendon said.

Still, recent polls show that public dissatisfaction with Congress is at historically high levels, and anti-incumbent sentiment is soaring.

Blendon made his comments during a session of The Forum at Harvard School of Public Health. The hourlong panel discussion, which was webcast live, focused on Congress’ failure to reach a budget agreement and the prospects for health care reform.

The session included Blendon, David Cutler, the Eckstein Professor of Applied Economics and professor in the HSPH Department of Global Health and Population, John Rother, president and chief executive officer of the National Coalition on Health Care, and Gail Wilensky, an economist and director of Medicare and Medicaid under President George H.W. Bush. The event, moderated by Reuters Boston Bureau Chief Ros Krasny, was sponsored by HSPH in collaboration with Reuters.

Though there is disagreement over what health care should look like in America, Blendon said that polls show that Americans’ priorities for government programs differ from those that dominate in Washington. While Americans are worried about the deficit and the national debt, they’d prefer to cut America’s overseas activities and raise taxes on the wealthy before cutting Medicare or Social Security.

Still, Cutler said, health care delivery in this country has to change if the nation is to deal with its fiscal problems. That’s because a great deal of the rapidly growing gap between government revenues and spending is due to health care costs, mainly because the baby boomers are retiring and going on Medicare. Not all of the savings has to come from health care cuts, Cutler said, but given the size of the problem, health care has to be on the table. Looking closer at health care spending, Cutler said, about a third goes to administrative costs, waste, and other areas where efficiencies can be found. Cutler said the heart of the battle over health care reform should be focused there.

With the failure of a congressional supercommittee to come up with budget-balancing cuts, there is great uncertainty over the immediate future of federal health care programs, Wilensky said. Medicare is facing a mandated 2 percent cut, but given Medicare’s share of the problem, that may wind up being a smaller cut than the program would have suffered under a congressional agreement. Still, Wilenksy said, coming on top of cuts already mandated by the Health Care Reform Act, another 2 percent trim could hit health providers hard. She is particularly worried about payments to physicians, which she said is the most badly broken part of Medicare.

A failing of the reform act is that it didn’t go far enough, panelists said. Though there are alternative health care models out there that show ways to improve care and lower costs, the reforms stopped short of mandating that one or another of them be adopted. The law does allow any successful pilot program to be scaled up dramatically.

Though Americans disagree over how to solve these questions, Blendon said the coming election should show which direction the nation wants to go.

Now, 15 years later, Kayden is an instructor in medicine at Harvard Medical School, an emergency physician at Harvard-affiliated Brigham and Women’s Hospital, and an authority in the humanitarian response to global disasters, both natural and man-made.

This semester, Kayden found herself coming full circle, spending her Wednesday evenings back in Emerson 101, but now standing at the front of the room teaching a course in humanitarian studies.

Kayden, an associate faculty member with the Harvard Humanitarian Initiative (HHI), said a scheduling quirk led the course, usually taught at the Harvard School of Public Health, to its Yard location. An unexpected surge in enrollment — 40 were expected but the total was nearly double that — left organizers scrambling for a room large enough to hold all the students. Emerson 101 was open.

Kayden has been around the world since those uncertain undergraduate days. She first went to New York to study at the Albert Einstein College of Medicine. She completed a fellowship in international emergency medicine at the Brigham, and now works in the  emergency room, directing the International Emergency Medicine Fellowship.

Her humanitarian work has taken her to provide aid after the 2005 Pakistan earthquake that killed 75,000, and the 2010 Haiti quake that killed more than 300,000. Kayden played a key role in saving lives in Haiti, and was among the first wave of Harvard-affiliated physicans to arrive in the devastated capital, Port-au-Prince. Within days, she realized that another facility was needed to handle the steady stream of severely injured patients coming from the city’s makeshift trauma centers.

Kayden, together with Assistant Professor of Medicine Hilarie Cranmer, director of the Brigham’s Humanitarian Studies Initiative and an associate faculty member of HHI, scouted a site outside of Port-au-Prince, near Fond Parisien. Within a few days, the two organized a field hospital that would eventually grow to contain more than 300 beds.

Reflecting on the path that took her back to Emerson 101, Kayden was philosophical.

“I applied as a bio concentrator, but then realized I’d be spending a lot of time [with that subject]. So I decided to stock my soul with something much more in the humanities and expand my reach,” Kayden said. “It was a nontraditional course for a pre-med student. I found it makes me a more concise and pointed thinker. In the emergency room, it helps.”

The humanitarian studies class that Kayden teaches is designed to give a head start to students interested in a path similar to hers. The class, open to students from Tufts University and Massachusetts Institute of Technology as well as Harvard, provides an overview of the challenges faced in a humanitarian disaster. The course examines human rights law, health care, provision of food and nutrition, water and sanitation, and safety and security. It hammers the lessons home with a real-world simulation in a nearby state park each spring.

“Diseases such as Huntington’s, Parkinson’s, and Alzheimer’s disease have different causative factors, but they share common themes — such as aggregation of misfolded proteins — and a unifying end point, the degenerative loss of neurons,” says the study’s senior author Dimitri Krainc of the MassGeneral Institute for Neurodegenerative Disease (MGH-MIND) and Harvard Medical School, where he is an associate professor of neurology. “Pharmacological targeting of Sirt1 may provide an opportunity for therapeutic development in HD and, more generally, in the neurodegenerative disorders of aging.”

HD is an inherited disorder caused by a mutation in the gene for a protein called huntingtin. Deposits of the abnormal protein accumulate within the brain, causing destruction of brain cells.  Symptoms of HD usually first appear in the middle years and worsen over the 10- to 30-year course of the disorder, leading to death from a variety of complications.  Sirt1 is an important regulator of the activity of proteins involved in many critical functions — including energy metabolism, inflammation, and stress tolerance — and recent studies have suggested it protects against the effects of several neurodegenerative diseases.

In experiments with a mouse model of HD, the researchers first showed that knocking out Sirt1 expression in the brain accelerated the appearance of HD-like pathology — such as aggregates of mutant huntingtin and increased cell damage in key areas of the brain.  In contrast, a strain of HD mice in which Sirt1 was overexpressed lived longer, with significantly less neurodegeneration and huntingtin aggregation, than did HD mice in which Sirt1 expression was unaltered.  Cellular experiments showed that Sirt1 overexpression directly protects neurons from the toxic effect of mutant huntingtin.

The MGH-MIND team also discovered a new target for Sirt1 activity in TORC1, a brain protein known to regulate several important neuronal genes, and found that the presence of mutant huntingtin interferes with the interaction between Sirt1 and TORC1, reducing expression of the regulated genes.  In the same issue of Nature Medicine, a research team based at Johns Hopkins School of Medicine reports similar neuroprotective effects for Sirt1.  Co-authored by members of Krainc’s team, the Hopkins study demonstrated that mutant huntingtin inhibits the activity of Sirt1, leading to deregulation of multiple Sirt1 targets, in two additional HD mouse models.

“Development of therapeutic agents for neurodegenerative diseases requires an in-depth understanding of the mechanisms that link the underlying biology with the resulting neuronal dysfunction,” says Krainc. “Developing and testing Sirt1 activators that protect against disorders like HD will require accurate information on Sirt1 activity in the normal and diseased brain.  We hope our studies can contribute valuable data to that effort, which will require collaborations with NIH, with industry, and with foundations such as the Cure Huntington’s Disease Initiative, one of the supporters of this study.”

Additional supporters of the investigation are the National Institutes of Health, the Hereditary Disease Foundation, and the Glenn Foundation for Medical Research.

Developed by brothers David Reshef, a current Harvard-MIT M.D./Ph.D. student, and Yakir Reshef  ’09, together with Professors Michael Mitzenmacher and Pardis Sabeti of the Harvard Departments of Computer Science and Organismic and Evolutionary Biology, respectively, the data-analysis algorithm is capable of quickly analyzing massive data sets to identify variables that may be related, enabling researchers to pick out potentially meaningful results they might otherwise have missed.

The paper describing the algorithm, published in the Dec. 16 issue of Science, applies the program to four data sets — microbiome data, genetic studies, global health data, and baseball statistics — in an effort to demonstrate its ability to detect relationships.

Just how massive is the flood of data coming from research laboratories?

One of the data sets used in the Science paper concerns the microbial flora of the human gut, and included almost 7,000 bacterial strains in 700 laboratory mice, for a total of more than 22 million possible relationships between bacterial strains, David Reshef said. If each possible relationship were printed on a single sheet of paper, the resulting stack of paper would be about 1.4 miles high, six times taller than the Empire State Building.

“It can easily become overwhelming,” said David. “That’s just one data set, and this one isn’t that large compared to some other data sets that are out there.”

Ironically, the brothers never set out to find a way to sift through huge amounts of data. They stumbled onto the problem three years ago, while working on ways to visualize large sets of public health data. ”As we worked, we realized that in order to visualize relationships in a large data set, you first have to decide which variables to examine,” said Yakir.

David added, “We didn’t know what kinds of things to look for in some of these data sets, and we needed a tool that would give us a quick summary of the data and tell us what variables were most strongly related. But it quickly became clear that this is a question that is much easier to pose than to answer, especially if you don’t know what types of patterns you’re looking for ahead of time.”

Over the next three years, the brothers, working with  Sabeti, assistant professor of organismic and evolutionary biology, and  Mitzenmacher, the Gordon McKay Professor of Computer Science and area dean for computer science, pursued their solution: an algorithm that forms the basis of a new approach to data analysis.

Though the idea of using a computer to analyze data is far from new, the brothers’ program is unusual in that it makes significant progress toward solving two problems that limited earlier efforts.

“If you have a data set with many variables and you want to know which ones are most strongly associated, you have to deal with the fact that there are different ways they can be related,” said David. “Some things, like the average life expectancy and the average children per woman in countries across the world, might be linearly related. But others, like flu prevalence over time, might show a more cyclical or periodic pattern because flu rates go up in the winter and drop in the summer. There are different tests that are good at capturing each of these different patterns. But making a tool general enough to capture them all is difficult.”

“This gets even more complicated because data are inherently noisy,” added Yakir. “If we have a tool that can find any pattern, we also want it to treat those patterns equitably. We want a score of 0.8 to indicate the same level of noise regardless of what the relationship is.”

Especially significant, Sabeti said, is the fact that the program can find multiple patterns at once.

To demonstrate the importance of finding multiple patterns, Sabeti turned to the data on global health indicators of the World Health Organization that were used in the paper. When female obesity rates are compared with income, she said, the data initially appear to fall along a parabola.  That is, initially, obesity rates rise in tandem with incomes. But at a certain point, increased income results in a drop in obesity rates.

While the program can easily spot such a relationship, this one turned out to be more complex.  Within the relationship between income and female obesity, there was a second trend occurring simultaneously. Data that at first glance did not appear to follow the previously described trend were actually indicators of different cultural norms. In this case, Sabeti said, the second trend in this relationship represents a cluster of nations with low incomes but very high obesity rates, in which obesity is culturally valued.

“This is just one example of what this algorithm is particularly good at detecting,” she said. “It allows you to find relationships that might be fairly complex or difficult to predict ahead of time, and it allows you to sort through things you wouldn’t have been able to deal with otherwise. As data sets get larger and larger, that becomes more and more important.”

Going forward, Mitzenmacher predicted the tool will prove powerful for researchers.

“What we were trying to design was a tool that we can use to understand data,” he said. “For many data sets, what you’re really doing is exploring. This test allows us to look at each of these comparisons, find those that exhibit an interesting pattern without specifying that pattern ahead of time, and score the strength of those correlations. This algorithm is a data exploration tool for the types of large data sets you see across all the sciences.”