The Science of Self-Agency: Dr. Nicolelis and the Walk Again Project

By Olivia Zhu

Screen grab from Univision of Juliano's robo-kick at the World Cup opening ceremony.

Screen grab from Univision of Juliano’s robo-kick at the World Cup opening ceremony.

Over the course of his 20-year career, Dr. Miguel Nicolelis has restored movement and self-agency to paraplegic patients.

On November 11th, as part of the Grand Challenge Seminar Series, Dr. Nicolelis captivated his audience by explaining the extensive process that culminated in Juliano, a Brazilian 29-year-old paralyzed from the chest downward in a car accident, performing the opening kick of the World Cup simply by using his mind.

Dr. Nicolelis has several faculty appointments in the Duke School of Medicine, Department of Psychology and Neuroscience, Institute for Brain Sciences, and Center for Neuroengineering. He has also written a book, Beyond Boundaries, about his work. His program, Walk Again, is supported by the Edmond and Lily Safia International Institute of Neuroscience in Brazil.

Dr. Nicolelis began making progress in 1999-2000 at Duke by developing electrodes that could record firing from multiple neurons. Using this technology, he determined which neurons were necessary for a monkey to move a joystick during a video game. Then, Dr. Nicolelis focused on creating a bypass that would bridge the mind directly to a computer, essentially removing the body as an intermediary.

He called this bypass a “Brain-Machine Interface,” or BMI, a term he coined at a cheese steak joint outside of Philadelphia. With the BMI, Dr. Nicolelis’s monkeys could play the video game without moving their arms or the joystick—they simply imagined themselves moving the joystick. The monkeys could even use their arms to do other tasks like eat or scratch themselves, creating a “third arm.”

Since then, with an extensive team of engineers, Dr. Nicolelis has implemented this technology by creating a IMG_1941hydraulically-powered exoskeleton that interprets a patient’s firing neurons and moves a patient’s legs accordingly.

He has also created artificial “skin,” which provides tactile feedback of movement to a patient’s upper body or, eventually, through an implant directly to the tactile cortex of the brain.

The technology is so accurate that patients report feeling “ghost limbs”—they believe that their legs are actually walking. The legendary Brazilian soccer player, Ronaldo, reportedly exclaimed “I’m moving!” with incredulity, when he was strapped to a chair testing Nicolelis’s technology.

Training with the exoskeleton also improves patients’ cardiovascular circulation, mental health, gastrointestinal health, and sensitivity in previously paralyzed areas.

Dr. Nicolelis is truly using science to stretch the boundaries of the human body.

Scents Are Key to Lemur Nightlife

LEMUR SUPERPOWER #457:  Some lemurs can safely digest cyanide in amounts sufficient to kill an elephant. Others can enter hibernation-like states to survive periods when food and water are in short supply. To add to their list of superpowers, lemurs also have especially keen powers of scent.

Buried in the nose of Fuggles the mouse lemur are specialized pheromone receptors that help her distinguish friend from foe in the dark of night, when mouse lemurs are active.

By Robin Ann Smith

If you could pick one superpower, consider taking inspiration from lemurs. Some lemurs can safely digest cyanide in amounts that would kill an elephant. Others can enter hibernation-like states to survive periods when food and water are in short supply. Still others have keen powers of scent, with the ability to find mates and avoid enemies in the darkness by smell alone.

Research by biologist and Duke Lemur Center director Anne Yoder suggests that the molecular machinery for sniffing out pheromones — much of which has gone defunct in humans and many other primates — is still alive and well in lemurs and lorises, our distant primate cousins.

Lemurs use scents to mark the boundaries of their territories, distinguish males from females and figure out whether another animal is friend or foe. When a lemur gets a whiff of another animal, specialized pheromone receptors in the lining of the nose transmit the information to the brain, triggering instinctive urges like mating, defense and avoiding predators.

The receptors are proteins encoded by a family of genes called V1Rs. First identified in rats in the mid-1990s, V1R genes are found in animals ranging from lampreys to humans. But the proportion of these pheromone-detection genes that actually functions varies greatly from one species to the next, Yoder said last week in a roundtable discussion hosted by Duke’s Science & Society program.

Randy the ring-tailed lemur scent-marks his territory. Photo by David Haring.

Randy the ring-tailed lemur scent-marks his territory. Photo by David Haring.

Studies suggest that as much as 90% to 100% of the pheromone-detection genes in humans consist of disabled pieces of DNA, called pseudogenes.

“Our pheromone-detection genes are so boring — we don’t have many of them, and almost all of them are broken,” Yoder said.

But in lemurs and lorises — whose ancestors split off from the rest of the primate family tree more than 60 million years ago — the proportion of pheromone-detection genes that is still intact is much higher.

In a study published this year, Yoder and colleagues analyzed the DNA of 19 species and subspecies of lemurs and lorises, looking for subtle differences in their V1R genes. They found that one group — the mouse lemurs — has the highest proportion of intact V1R sequences of any mammal yet studied.

To find out which genes are linked to which scents, Yoder and her colleagues plan to take DNA sequences from pheromone-detecting genes in lemurs, insert them into mice, and expose the mice to different scents to see how they respond.

An ability to sniff out the right mates — and avoid being seduced by the wrong suitors — may have served as a mating barrier that allowed lemur species to diverge after arriving in their island home of Madagascar, helping to explain how the more than 70 living species of lemurs came to be, Yoder says.

The Mystery Behind the Camel Statue

Knut Schmidt-Nielsen

A file photo of the real Knut Schmidt-Nielsen, not the bronze one, standing with the enigmatic camel statue dedicated to him and his work.

By Olivia Zhu           

The camel statue between the Biology Building and Gross Hall is a staple of Duke’s campus, but the significance behind this landmark is generally unknown.

On Monday, September 22, faculty from the Biology Department gathered for a dedication to remember the man behind the camel statue (or rather, in front of it), Dr. Knut Schmidt-Nielsen, who died in 2007.

Knut Schmidt-Nielsen, who would have turned 99 this Wednesday, was “the father of comparative physiology and integrative biology” and a James B. Duke professor at Duke’s Biology Department starting in 1952.

Schmidt-Nielsen studied the physiology of the camel’s nose, received the International Prize for Biology, and wrote the authoritative text on animal physiology.

Dr. Stephen Wainwright, who was present at the dedication, commissioned the camel to British sculptor Jonathan Kingdon, who finished the bronze camel statue in 1993. The inscription for the statue, “Tell me about yourself, Camel, that I may know myself,” encapsulates Schmidt-Nielsen’s outlook on physiology.

According to Dr. Steven Vogel, who was recruited to Duke’s faculty by Schmidt-Nielsen 49 years ago, Schmidt-Nielsen was actually shy and rather uncomfortable with the statue of himself. Vogel reported that Schmidt-Nielsen greatly advanced the zoology department with his high standards and “great charm and urbanity.”

“You could never say no to Knut,” Vogel said. Schmidt-Nielsen was also reportedly  “a very serious wine drinker”—accordingly, the dedication ceremony ended with wine and champagne.

To learn more about Knut Schmidt-Nielsen, read Vogel’s memoirs or a recommended autobiography, The Camel’s Nose.

Knut Schmidt-Nielsen

The statue as it appears now, with Knut in bronze. (File photo)

Chimpanzee Voices From the Past Go Digital, Open Access

By Karl Leif Bates

A treasure trove of chimpanzee audio recordings from the 1970s has been posted on an open access site for study by a team that includes Evolutionary Anthropology chair Anne Pusey, who also directs Duke’s Jane Goodall Institute Research Center.

An image from the  Scientific Data paper shows the bulky, analog field gear used for making recordings in the 70s.

An image from the Scientific Data paper shows the bulky, analog field gear used for making recordings in the 70s.

Announced this week in the open access journal Scientific Data, the collection includes more than 1,100 recordings made of 17 immature chimpanzees, totaling 10 hours. The recordings were made between 1971 and 1973 by the late Hetty van de Rijt-Plooij and Frans X. Plooij, Dutch researchers working at Goodall’s study site in Gombe National Park, Tanzania.

Though the Plooij collection was catalogued and annotated — notes which Frans then translated from Dutch to English with support from the National Evolutionary Synthesis Center in Durham — the massive collection has never been studied. Preparation of the metadata for the audio recordings was supported by the National Science Foundation (LTREB-1052693).

What the newly digitized recordings represent is the opportunity to study the development of vocalization over a chimpanzee’s lifetime, Pusey explained. Many of the individuals who were recorded as infants and adolescents subsequently turn up in recordings made by Peter Marler in 1967, Charlotte Uhlenbroek in 1991–1993, and Lisa O’Bryan in 2009–2010.

The authors say, “comparing their adult recordings with their infant/juvenile recordings might be an especially effective way of studying vocal development.”

They’re also just kind of fun to listen to. (Browse the entire catalog here.)

Jane Goodall visited Anne Pusey and the archive of Gombe field notes at Duke in 2011. (Duke Photo)

Jane Goodall visited Anne Pusey and the archive of Gombe field notes at Duke in 2011. (Duke Photo)

This work is the latest in a trend of Duke becoming one of the world’s great centers of longitudinal primate studies. Pusey’s work on this audio collection joins the more than 50 years of observational notes and data from Gombe now housed at Duke; Susan Alberts has led the assembly of life history data from nine different primate field studies into a single database. And nearly 50 years of captive lemur data from the Duke Lemur Center was digitized and just posted a few weeks ago. (Pro version on Scientific Data.)

Math and Comp Sci Junior Studies Fruit Flies

By Ashley Mooney

dorsal closure

Dorsal closure is a stage in fruitfly embryonic development that is used to study wound-healing.

Roger Zou, a computer science and math major from Solon, Ohio, is working on creating more efficient ways to study wound-healing in fruit flies. It turns out that the way fruit flies heal actually has implications for how mammals heal too.

The junior is developing computational methods that can more accurately quantify cellular properties of fruit flies. As fruit fly embryos develop, he tracks cells through space and time to learn more about a process called dorsal closure. It’s a developmental stage that is similar to wound healing, where a gap in the embryo’s epithelium—which is like its skin—is closed by the coordinated effort of different types of cells. (see movie below)

Roger Zou is a junior spending the summer in Dan Kiehart's lab.

Roger Zou is a junior spending the summer in Dan Kiehart’s lab.

“It’s fun to study the morphological forces because it’s not entirely understood how organisms develop,” Zou said.

In his analysis, Zou uses a laser under a microscope to make cuts on areas of the fly embryos. After making cuts, Zou uses computational methods to measure the wound healing.

Beyond collecting such data, Zou is developing a computer program that analyzes images from the microscope more accurately.

Zou has worked in Biology Professor Daniel Kiehart’s lab since his freshman year. His project was originally a component of a graduate student’s dissertation, but after she graduated, he continued some aspects of her research.

His project has been funded by the Dean’s Summer Research Fellowship for two consecutive summers. He also has done several independent study projects. Although Zou is planning on publishing his research this summer, he will likely use the data eventually to do a senior thesis.

Several of Zou’s math and computer science classes have given him a background in the techniques needed to use a computer to analyze large sets of image data, he said.

“My favorite thing about my research is the ability to learn new things independently,” Zou said. “[Kiehart] is very good at leading me in the right direction but allowing me to be very independent and I think because of that I’ve been able to learn a lot more and learn from my mistakes.”

Outside of his research, Zou is a teaching assistant for the computer science class Data Structures and Algorithms. He also tutors  Duke students in organic chemistry and middle school children in math through the America Reads*America Counts program. And he also does web development for The Chronicle, Duke University’s independent student newspaper.

After graduating, Zou said he hopes to pursue a PhD in either computational biology or computer science or maybe go for a combined MD-PhD program. No matter which program he chooses, Zou said he wants to continue doing research.

Duke Undergrads Sink Their Teeth into Evolution Research

Undergraduates Ben Schwartz (left) and Amalia Cong (center) have spent the past year studying enamel evolution in the labs of Christine Wall (right) and Greg Wray (not pictured).

Undergraduates Ben Schwartz (left) and Amalia Cong (center) have spent the past year studying enamel evolution in the labs of Christine Wall (right) and Greg Wray (not pictured).

By Erin Weeks

The evolution of thick tooth enamel helped turn our species into hard food-chomping omnivores, and two undergraduates are taking a bite out of research to unravel how that happened. Amalia Cong and Ben Schwartz are building on the work of a recent paper that identified precisely where in the human genome natural selection worked to give our species thick tooth enamel. The original study looked only at the potential role of four genes with a known role in tooth development — so now the team is broadening their scope.

“They’re really excited to expand out and push the envelope on new genes,” said Christine Wall, associate research professor of evolutionary anthropology and one of the authors of the paper, along with professor of biology Greg Wray.

Cong and Schwartz arrived in the Wall and Wray labs last summer through a special research session at Duke, the Howard Hughes Vertical Integration Partners (VIP) Program. For ten weeks, they received a crash course in primate evolutionary genomics.

“They had very little time, and the progress they made was astounding,” Wall said. “The success that they had is really a testament to how hard they worked. This has developed into their own research.”

“We’ve begun to expand our tooth enamel gene analysis to include proteins in conjunction with the RNA in order to gain a more holistic understanding of the evolutionary differences that exist between chimpanzees and humans,” Schwartz said. He will continue to work in the lab through this summer, turning the work into a senior thesis.

“One of our goals was to look at the relative expression of these few genes,” Schwartz said, which they’ve done by comparing tooth development in primates of different ages. “Our results correlated very heavily with known functions of these genes in other animals, such as rats.”

The experience has given both students a taste for research, which they hope to continue doing after graduating from Duke. Cong, who hails from a small city outside of Toronto, will be attending dental school in the fall, while Baltimore native Schwartz is interested in pursuing a joint MD/PhD.