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Max Leung, Caped Crusader Against DNA Damage

By Becca Bayham

His lab colleagues call him Batman, the Toxic Knight.

To the rest of the world, he is Maxwell Leung, a PhD candidate in Duke’s environmental toxicology program. For the past five years, Leung has worked in the lab of Joel Meyer (AKA “Super-enviro-man”) fighting for environmental justice with pipettes and PCR machines.

Leung spoke about his research Jan. 27 as part of the Nicholas School’s continuing series on toxicology. Leung studies how exposure to certain environmental chemicals can affect organisms’ later-life development by damaging their DNA.

Cells contain two types of DNA: nuclear DNA (found in the nucleus) and mitochondrial DNA (found in mitochondria, which generate most of a cell’s energy).

“When people talk about DNA damage, they are usually referring to DNA damage and revision occurring in nuclear DNA,” Leung said.

A ligase enzyme repairs damage to nuclear DNA (National Institute of General Medical Science)

For the most part, special packaging and multiple repair mechanisms protect nuclear DNA from harm. However, mitochondrial DNA lack certain repair mechanisms, and little is known about their packaging. In the lab, Leung evaluated damage to both types of DNA by exposing worm larvae to short bursts of UV radiation. He found that, while nuclear DNA damage was partially repaired during the 24 hours between exposures, mitochondrial DNA damage continued to accumulate.

Further study of the exposed worms suggested that mitochondrial DNA damage at an early life stage can cause adverse effects such as reduced energy production, DNA transcription and oxygen consumption in adults. Given this connection, Leung sought to identify environmental chemicals that are capable of damaging mitochondrial DNA. Of the six chemicals he tested, one targeted mitochondrial DNA over nuclear DNA, and caused visible neurological effects: paraquat, a widely-used herbicide.

Which raises the question: if one out of six tested chemicals had this effect, then how many other environmental chemicals could cause that type of damage?

Unfortunately, mitochondrial DNA damage disproportionately affects neurological tissues; neurons require a great deal of energy and thus contain large amounts of energy-producing mitochondria. Studies have found strong associations between genes in mitochondrial DNA and neurodegenerative disorders such as Parkinson’s disease.

After the lecture, I spoke to Leung about why he decided to study science, and how he came to Duke.

“When I was in junior high, there was a TV show called ‘Success Stories’ in Hong Kong, featuring a number of famous Chinese scientists pursuing scientific careers in U.S. They went on to become National Academy members, win Nobel Prizes, and make important contributions to science and our world. That left an impression on me.”

Now, Leung hopes to write his own success story. He received his undergraduate degree in Food and Nutritional Science from the University of Hong Kong, and a master’s degree in Food Toxicology from the University of Guelph in Canada.

Leung came to Duke in 2007, following a visit to Joel Meyer’s newly-established environmental toxicology lab. At the time, the lab was “literally empty,” with just four PCR machines and a lab technician from Canada. Fifteen researchers work in the lab now, and each has been christened with their own superhero nickname including such characters as “Terror Byte,” the “Nano Ninja,” and “Wonder Worm Woman”.

“I enjoy the people I come across in science more than the science itself,” Leung said. “I enjoy doing experiments, giving talks and writing papers, but it is always the interesting people that I get to know through these activities that keep me going everyday.”

Composing music with Xbox Kinect

By Ashley Yeager

Ken Stewart uses his motions and an XBox Kinect to narrate, musically, a dance by Thomas DeFrantz. Credit: Duke University Dance Program.

To watch Ken Stewart dance in front of his Xbox Kinect gives a whole new meaning to the “Dance Your Ph.D.” contest.

Stewart, a graduate student in the music department and a composer, is using the camera, along with specialized computer software, to narrate dance with sound. He demo’ed the program while walking an audience through his imnewhere, or I’m new here, composition of dance professor Tommy DeFrantz’s journey to Duke.

The Jan. 27 presentation was part of the Visualization Friday Forum and gave attendees a behind-the-scenes look at the research and mathematics behind Stewart’s new, “more expressive way” to write music.

With the Kinect, which has motion-detection technology for interacting with video games, Stewart can transform his gestures into sound, intimately controlling the loudness, pitch and rhythmic intensity of the score he creates. The system records 15 points on a controller’s body, including his head, neck, shoulders, knees and feet.

Using a library of sounds, the controller can then correlate and choreograph a composition, using the computer to calculate angles between his hands or distance between his body and the camera. These angles are converted to become the musical notes.

The work, Stewart says, gives him a way to use his ears and actions to “feel out” a song. He concedes that there are hiccups between how he moves and the sounds created, but, he says he thinks that the imprecision adds to the expressivity of the composing process.

Stewart said he and DeFrantz are still working on imnewhere. They plan to expand the piece to 15 minutes and will perform it again in Grand Rapids, Mich., Berkeley, Calif. and Belfast, UK.

'Knowsphere' could solve climate problems, Revkin argues

By Becca Bayham

Does the world seem a little angsty-er to you? It should, it’s got way more adolescents.

“There were only a billion people [on Earth] in 1800; now we have a billion teenagers,” said Andrew Revkin, a prize-winning journalist and New York Times blogger, during a lecture on Jan. 18.

“Is this a sign of overpopulation?” someone in the audience joked, referring to the jam-packed classroom.

Likely not, but, as Revkin discussed, resource limits and an explosive human population growth may eventually cause population or economic declines.

“We don’t seem to have distinguished ourselves from bacteria on a plate of agar yet,” Revkin said. “Science is saying hey, hey, there’s an edge to the dish! But we’re still in go-go-go mode.”

The fact that we will reach the edge of the dish is undeniable — and it won’t be pretty. To illustrate, Revkin showed a picture of Black Friday shoppers fighting over a sale item.

“Can you imagine everyone doing this?” he said.

Unfortunately, we humans are historically bad at confronting problems that don’t affect us here-and-now. If in doubt, see our lackluster response to the national debt. Or global climate change, for that matter (a topic Revkin often blogs about).

“There’s a big chunk of everyone who just doesn’t want to deal with global warming, to tell you the truth… it’s hard, it’s complex, it’s laden with layers of complicit uncertainty. What is it and what do you do about it?”

Revkin believes that global connectedness, powered by the internet, offers a solution to the many problems humanity will face in coming years.

Communication between people — sharing information and exchanging ideas — has long fueled our economy and fostered human progress. According to Revkin, a network of collaborating schools, libraries, businesses and other institutions (a “knowsphere”) could help combat problems ranging from natural disaster preparedness to the treatment of diseases.

“Much of human progress can be charted in relation to our linkages with others,” he said.

In the 1920s, philosophers Vladimir Vernadsky and Teilhard de Chardin conceptualized the idea of a “noosphere” (from the Greek “nous”, mind and sphaira, “sphere”), a philosophical sphere of intelligence around the Earth that humans could draw from — a planet of the mind. Back then, it was just an idea.

“But now, it’s happening,” Revkin said.

Is He Conscious? Does He Want To Be?

Terri Schiavo of Florida, whose vegetative state and right to life became a national issue in 2005

By Jeannie Chung

The difference between a dead man and a man in a vegetative state used to be a thin line of whether
or not the body was still functioning. But what if the vegetative man is still conscious? That brings
the distinction into a whole new level.

Philosopher Walter Sinnott-Armstrong gave a talk titled “Is he conscious? Does he want to be?” at the Trent Center for Bioethics on Friday, Dec. 9. He discussed clinical studies which have shown that despite the unresponsive display, patients in vegetative state may be still conscious. With assistance from an fMRI or an EEG scan, doctors can tap into the patient’s brain activity and “read their thoughts.”

The scanning study’s control was patients who received severe brain trauma and were confirmed to be in a vegetative state. The studies focused on the specific brain activity when the patient was commanded to “think about tennis” and the brain activity that occurred when the patient was commanded to “imagine anything other than tennis.” The distinctive brain activities were then coupled with a series of yes or no questions. If their answer was yes, the patient was told to think about tennis and if their answer was no, the patient was told to think about navigating through a house. In one case study, the patient answered five out of seven questions right by showing brain activity associated with tennis to questions for which an affirmative was the correct answer. The other two questions showed no response, and the doctors assumed the patient had gone to sleep.

This confirmation of consciousness in some vegetative patients brings up an ethical issue. Those at the bedside can now ask questions, including “do you want to live?” The vegetative patient’s answer to such a question may inform the ethical issue that arises each time we worry about “pulling the plug” on a clearly “living” person.

 

 

EPA regulation adds jobs, despite partisan myths

By Becca Bayham

“Environmental and health threats are unambiguously non-partisan concerns,” EPA administrator Lisa Jackson said during a Dean’s Series lecture at Duke, Dec. 6. “The quality of our air and our water has an effect on our way of life whether we live in a red state or a blue state.” (View Jackson’s talk at Duke on Demand)

And yet, Republican leadership has orchestrated 170 votes against environmental protection laws since the beginning of this year. According to Jackson, these votes were mostly in response to myths. She cited one false, but commonly used statistic that the EPA plans to triple its budget and hire 230,000 new regulators (a 1,200% increase over its current 17,000).

“It’s striking how easy it is to get information to the American public that is scary or misleading,” Jackson said.

Back in 2009, an anonymous source leaked a series of emails exchanged between British climate researchers, setting off a controversy dubbed “Climategate” by one climate skeptic blogger. The emails were the subject of intense media coverage, even though later investigations found no evidence of fraud. However, when a leading climate skeptic recanted his beliefs earlier this year, the event received very little media attention.

“Right now there are two visions competing for the future of our country and our economy,” Jackson said.

The first is a trust in science and a belief that our country can institute changes that will both protect the environment and create a surge of new jobs. The second vision, according to Jackson, is that “moving forward requires rolling back.” Namely, that the U.S. should maintain policies that protect polluters, thereby preserving a small number of jobs.

But, “a strategy to grow our economy by doing less is not sufficient to deal with the problems we have now,” Jackson said.

Furthermore, actions that benefit the environment can also benefit the economy, she argued. Contrary to belief, smart regulations generate jobs rather than eliminate them. Congress will soon pass a mercury standards act to limit toxic emissions from smokestacks. This legislation will create an estimated 31,000 short-term construction jobs and 9,000 long-term jobs. The EPA predicts that the standards will save 17,000 lives a year (via reduced incidence of heart attacks, asthma and acute bronchitis).

Most Americans have grown up in a country regulated by the EPA. Thus, people may underestimate how much the agency has done during its 40-odd years of existence, Jackson said. Americans enjoy clean air and water, things that are not a given in other countries. However, budget cuts threaten enforcement while toxic substances such as mercury, lead, VOCs and nitrous oxides still pose a threat.

“The future of the environmental movement is educating the public that the threat is not done,” Jackson said.

However, she finds ample reason for hope in the actions that communities — red and blue alike — are taking to improve efficiency and reduce their environmental impact.

“I think that if we do our jobs right, we will keep moving forward,” she said. Not quickly, “but we’re not moving backwards either.”

Solving problems with iPad (or Android) apps

eCLIP iPad applicationBy Becca Bayham

When a patient comes into the E.R. with a lung problem, doctors usually put them on a ventilator. Unfortunately, this procedure helps some patients, but hurts others. Doctors have difficulty predicting which will be the case, due to a lack of data on risk factors. A predictive model was recently developed to solve this problem, but the calculations require more time and information than E.R. doctors usually have.

Enter Raquel Bartz, an emergency room doctor at Duke Hospital. She envisioned an iPad application where doctors and family members could input the necessary medical information, and the app would spit out the treatment protocol for a particular patient. Bartz turned to Richard Lucic and Robert Duvall’s Software for Mobile Devices class (COMPSCI 196) to make her idea a reality.

The result? An application called eCLIP, developed by students last Fall and available now in iTunes’ App Store. (See photos at left)

eCLIP is one of five applications created by students during the two semesters COMPSCI 196 has been offered. Lucic and Duvall described the course — and its various student-produced applications — at last week’s Visualization Friday Forum, sponsored by the Visualization Studies Initiative (http://visualstudies.duke.edu/) and Duke’s computer science department.

“We’re trying to teach students about the mobile app world,” Lucic said. “In addition, we’re trying to teach students about the software development process, from conception of an idea to delivering a product to a client.”

Lucic emphasized the importance of teamwork, as well as the value of visual design skills for increasing a product’s appeal. Furthermore, user testing is a critical step for identifying problems.

This semester, nine clients pitched their application ideas. Students voted for their favorite projects, and three were ultimately chosen:

  • Ajay Patel, IT Manager in the Duke Cancer Center, wanted a way to track medical samples during processing and reduce human error
  • Allison Besch, educational curator for the North Carolina Maritime Museum, wanted a fun, educational tool for teaching marine resource conservation to 4th graders
  • Rachel Cook, Duke alumna and former futures trader, wanted an app to encourage microlending and bridge the gap between lenders and borrowers

Each client worked with a team of 3-4 students, and met with them every other week to discuss the team’s progress.

“A lot of students are learning how to code mobile apps for the first time, so there’s only 6-7 weeks of actual coding time,” Duvall said.

Despite the time crunch, students try to present a finished product to their clients by the end of the semester. But who keeps the app going after the course’s conclusion?

“What we’re trying to do is have the students provide enough documentation and write their code well enough that the app can be maintained by the client’s organization,” Lucic said. “Clients have been thrilled with the experience. I think we’ve done a superb job of meeting their needs, as much as you can in a one-semester course.”

The Paul Farmer Way of Life

By Prachiti Dalvi

One of Duke’s most distinguished alumni and one of global health’s biggest names, Paul Farmer, MD, PhD, discussed his latest book “Haiti After the Earthquake at Duke on Saturday afternoon.

(See Complete Video of his Talk)

So, what should Duke students take from this individual who just like us lived in Wannamaker, wrote for the Chronicle, and once roamed this Gothic wonderland? “Start as early as you can.”

Upon graduating from Duke in 1982 with a BA in medical anthropology, Farmer spent a year in Haiti: a decision that would help him become the kind of physician he always imagined himself as and would help him uncover his lifelong passion. Farmer then returned to Harvard University (which he humorously referred to as “the Duke of the North”) to obtain his MD and PhD in medical anthropology.

Now, Dr. Farmer is Chair of the Department of Global Health and Social Medicine at Harvard Medical School and the Kolokotrones University Professor, one of the highest honors that can be granted to a faculty member. He has been awarded the Conrad N. Hilton Humanitarian Prize and the MacArthur Foundation Genius Award for his work.

“We must counter failures of imagination.”

Just five years after leaving Duke, Farmer co-founded Partners in Health (PIH), an international health organization committed to improving health care in developing countries. This nonprofit organization focuses on building sustainable health care systems rather than simply treating patients. However, Farmer believes that their biggest challenge lies in breaking the cycle of poverty and disease. And, in essence, helping the Haitian community imagine a world where these hurdles can be overcome.

PIH aids developing countries establish sustainable health systems by recruiting community members to be involved in all aspects of designing and implementing a health system. The hospitals that PIH helps establish in Haiti are operated by Haitian doctors, nurses, and medical students.

This nonprofit organization is grounded in the belief that health and education are vital for development. Partners in Health works with partner organizations and national ministries of health to operate projects in twelve different countries all over the globe.

“You might lose the battle, but you won’t lose the war.”

When a magnitude 7 earthquake struck near Port-au-Prince, Haiti’s capital, on January 10, 2010, the effects were everlasting. The toll the earthquake took on Haiti was augmented by the lack of resources and the unexpectedness of the disaster. In fact, the earthquake depleted resources to the extent that it was difficult for Haitian firms to meet minimal process requirements. Resources had to be brought in from outside sources.

One of the most striking issues was facing the largest epidemic of cholera Haiti had ever witnessed. Academic institutions such as Duke and Harvard played a huge role in providing medical relief and “we can be proud of the role academic medicine played” during this critical time period. Farmer claims “Universities have a role to play” in helping bring healthcare equality to developing countries.

Although the earthquake brought with it a great deal of destruction, it also brought with it the opportunity to invest resources in building a sturdier foundation for the health care system. For example, rather than accentuating either treatment or prevention we can now integrate treatment and prevention.

“It’s wonderful to be around, hopeful, optimistic, young people like you.”

Dr. Farmer emphasized the role teaching plays in innovation. According to Farmer, innovation comes from change. Change comes from critical feedback loops. And, critical feedback loops come from discussion. Education is critical in generating conversation and new ideas. As one ages, pessimism begins to sink through and we need fresh minds to bring light to the optimistic aspects of life.

Yet Farmer’s work in Haiti remains fresh and optimistic. “Although Haiti does not have a teaching hospital, doesn’t it deserve a good teaching hospital?” asks Farmer. Currently, PIH is constructing Mirebalais Teaching Hospital. When completed, the hospital will house 320 beds, serve approximately 500 patients daily and will train the next generation of Haiti’s doctors, nurses, and medical professionals.

 

Sharing is caring, when it comes to scientific data

By Becca Bayham

Worms don’t typically evoke a sense of awe. But C. elegans nematode worms — all 558 cells of them — played an important role in how scientific data is shared today.

Scientists Robert Waterston and Sir John Sulston described this connection during the James B. Wyngaarden Distinguished Lecture on Nov. 14, sponsored by the Institute for Genome Sciences and Policy. [Watch the whole lecture – 1 hour, 9 minutes)

During the 80s, Waterston and Sulston were unraveling the nematode genome at their University of Cambridge lab. Worms make good subjects for study because they are finite, transparent and genetically manipulatable.

The Worm Breeder's Gazette - Volume 8, Issue 2When Waterston moved from Cambridge to Washington University in St. Louis, he felt isolated from the research community he’d left. However, an informal and creatively-covered publication — the Worm Breeder’s Gazette (see photo at left) — helped bridge that physical divide. Researchers used the Gazette to share short summaries of their discoveries.

“Through this very informal means, the community was made aware of what was going on, and invited to share in it,” Waterston said. “Indeed, it worked spectacularly. Now we knew not just these anonymous pieces of DNA, but where they belonged. And that made [the data] much more useful for us and the community.”

Waterston and Sulston were the first to sequence a multi-cellular organism’s genome. Following their success with worms, the two moved on to the holy grail of science at the time: the human genome.

In terms of data sharing, “human genetics was the polar opposite of the worm field. Human geneticists held things very close to their chests,” Waterston said.

In 1996, the two scientists joined other researchers at a conference in Bermuda to discuss how human genome data should be handled. Should it be stored in proprietary databases, with limited access? Or shared freely with the world? Waterston and Sulston advocated for the latter, and this opinion ultimately prevailed. If it hadn’t, the humane genome story might have ended differently — or not at all. Data sharing “kept the lines of communication open” between researchers, Waterston said, and greatly facilitated the sequencing process.

Sure enough, following the human genome’s completion in 2000, the entire sequence was released into the public domain. Public data sharing has become standard practice for other animal genomes and other areas of science. However, even though Waterston and Sulston’s efforts encouraged data sharing on a massive scale, the tendency towards secrecy still exists.

“Pushing for more open science continues to be important,” Waterston said. “The nature of science is that private initiatives continue to push on public domain. If we don’t push back, we’re going to be the poorer for it.”

A sip or quick dip could change your DNA

By Ashley Yeager

Micronuclei in mammalian cells form when DNA undergoes stress and not all the material makes it into the two new nuclei of a dividing cell. Credit: CRIOS.

As a long-time swimmer, I was a bit disturbed when EPA scientist David DeMarini said he had scientific evidence showing that extra time in the water could damage my DNA or even raise my risk for bladder cancer.

The damage, he said, comes from leftover chemicals from the treatment process in which bromine and chlorine are used to kill E. coli and other bacteria in drinking, bath and swimming water.

There are at least 600 of these chemicals, called disinfection byproducts or DPBs, released into the water after treatment, and DeMarini has spent more than a decade identifying them and how they interact with the molecules in our bodies.

Through his research, he has shown that many of the DPBs, whether ingested, inhaled or absorbed through our skin, can change our DNA. Yet, only 11 DPBs, all from drinking water, are regulated in the U.S., and none are regulated in any of the other developed countries, DeMarini said during a Nov. 11 Integrated Toxicology & Environmental Health seminar at Duke.

No one really thought about pool water until about five years ago because “people always thought swimmers weren’t at risk for anything. They thought, ‘swimmers are healthy, so why waste our time studying them,’ ” DeMarini said.

That assumption changed in 2007. Researchers in Spain found, based on interviews, that swimmers had a 1.6-fold increase for bladder cancer. Then, in 2010, DeMarini and his colleagues showed that after a 40-minute workout, swimmers’ cells created micronuclei, suggesting damage was done to the DNA so that another nuclei formed as the cell began to divide.

Together, the teams were able to identify a specific gene that makes some individuals more susceptible to DNA damage from DPBs, further increasing their cancer risks. About 28 percent individuals in the U.S. have this gene.

That doesn’t mean we should stop swimming, bathing or drinking municipal water though, DeMarini stressed. He said that the known benefits of drinking, bathing with or swimming in chlorinated water are still much greater than the potential health risks from DPBs.

“You’re naïve, though, if you think that the environment you live in is pristine,” he said. “It’s not.”

But to keep pools a little cleaner and reduce the burden of disinfection byproducts, he suggested not peeing in the water and showering before taking a dip. Drinking pool water is not a good idea either.

Particles on Ice

By Ashley Yeager

Protons, neutrinos and photons take different paths toward Earth. Physicists have to figure out their paths to determine where the particles came from. Credit: Deutsches Elektronen-Synchrotron.

Imagine nabbing the cover of the journal Science. Now, imagine doing it without making a single discovery. For University of Wisconsin physicist Francis Halzen, those dreams came true in 2007.

“We hadn’t done anything by then,” he said during a Nov. 9 physics colloquium as he described the experiment called IceCube.

IceCube is a neutrino detector buried deep in the ice of Antarctica. It did not begin full scientific operations until May 2011. So why did it claim prime Science real estate four years earlier?

Because Halzen and his team were the clear winners in a race, which began in the 1970s, to build a kilometer-wide bucket to capture particles called neutrinos.

To cover just over a half mile of Antarctica with such a detector, Halzen’s team engineered 5,000 neutrino buckets to sit on 86 electronic wires, a bit like strings of Christmas lights. The team then fed each string a mile and a half into the ice near the South Pole.

The idea was that the instrument would detect blue light coming from the reaction of a single neutrino crashing into an ice atom. From that reaction, the physicists could start to tease apart where neutrinos and other high-energy showers of particles, called cosmic rays, come from. Now, the team has also begun adding to the instrument so it can probe what dark matter and dark energy are.

This diagram, superimposed on an aerial photo of the South Pole Station, shows where the 86 detector strands sit. Courtesy of: Tom Gaisser, Univ. of Delaware.

Halzen said studying neutrinos is a lot like taking an X-ray, rather than a normal photo, of the galaxy and the universe. He added that even though there are some promising data points in IceCube’s preliminary scans, no one should get too excited. The neutrino buckets haven’t really seen anything, yet.

 

It’s a bit like the Large Hadron Collider not seeing the Higgs boson, he said. If scientists don’t see what they are looking for, it will be really interesting and may call for a re-write of the physics textbooks.

But, Halzen said, “I can tell you, we want to see something,” and, doing it before next year, when the discovery of cosmic rays turns a century old, would fulfill another of his physics dreams.

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