Quinn Eastman

Brain enhancement: can and should we do it?

The Emory Center for Ethics and Emory’s Neuroscience Graduate Program recently co-hosted a symposium discussing the ethics of brain-enhancing technologies, both electronic and pharmacological.

Georgia Tech biomedical engineer Steve Potter explained his work harnessing the behavior of neurons grown on a grid of electrodes. The neurons, isolated from rats, produce bursts of electrical signals in various patterns, which can be “tuned” by the inputs they receive.

“The cells want to form circuits and wire themselves up,” he said.

As for future opportunities, he cited the technique of deep brain stimulation as well as clinical trials in progress, including one testing technology developed by the company Neuropace that monitors the brain’s electrical activity for the purpose of suppressing epileptic seizures. Similar technology is being developed to help control prosthetic limbs and could also promote recovery from brain injury or stroke, he said. Eventually, electrical stimulation that is not modulated according to feedback from the brain will be seen as an overly blunt instrument, even “barbaric,” he said.

Mike Kuhar, a neuroscientist at Yerkes National Primate Research Center, introduced the topic of cognitive enhancers or “smart drugs.” He described one particular class of proposed cognitive enhancers, called ampakines, which appear to improve functioning on certain tasks without stimulating signals throughout the brain. Kuhar questioned whether “smart drugs” pose unique challenges, compared to other types of drugs. From a pharmacology perspective, he said there is less distinction between therapy and enhancement, compared to a perspective imposed by regulators or insurance companies. He described three basic concerns: safety (avoiding toxicity or unacceptable side effects), freedom (lack of coercion from governments or employers) and fairness.

“Every drug has side effects,” he said. “There has to be a balance between the benefits versus the risks, and regulation plays an important role in that.”

He identified antidepressants and treatments for attention deficit-hyperactivity disorder or the symptoms of Alzheimer’s disease as already raising similar issues. The FDA has designated mild cognitive impairment associated with aging as an open area for pharmaceutical development, he noted.

James Hughes, a sociologist from Trinity College and executive director of the Institute for Ethics and Emerging Technologies, welcomed new technologies that he said could not only treat disease, but also enhance human capabilities and address social challenges such as criminal rehabilitation. However, he did identify potential “Ulysses problems”, where users of new technologies would need to exercise control and judgment.

In contrast, historian and Judaic scholar Hava Tirosh-Samuelson, from Arizona State University, decried an “overly mechanistic and not culturally-based understanding of what it means to be human.” She described transhumanism as a utopian extension of 19th century utilitarianism as expounded by thinkers such as Jeremy Bentham.

“Is the brain simply a computational machine?” she asked.

The use of military metaphors – such as “the war on cancer” – in the context of mental illness creates the false impression that everything is correctable or even perfectable, she said.

Emory neuroscience program director Yoland Smith said he wants ethics to become a strong component of Emory’s neuroscience program, with similar discussions and debates to come in future years.

Posted on by Quinn Eastman in Neuro Leave a comment

Talent in the pipeline

The Pipeline program, an initiative led by Emory medical students to improve college readiness and promote health career interest among Atlanta high school students, held graduation ceremonies Wednesday night at Emory University School of Medicine.

Graduating seniors and their mentors. All 19 seniors have at least one college acceptance, reports Pipeline co-founder Zwade Marshall.

Leaders at South Atlanta School of Health and Medical Sciences credit Pipeline with sparking interest in health science careers and bolstering attendance and academic performance.

“We see more leadership, not just in class but in the whole building,” says Edward Anderson, a teacher who coordinates the program. “Students are picking up the torch and running with it. I believe they will be future leaders and have a great impact.”

Sophomores, juniors, and seniors have access to a distinct curriculum with a classroom component, one-on-one mentoring by Emory undergraduates, and hands-on demonstrations. Sophomores explore infectious diseases and HIV/AIDS. Juniors study neuroscience. And seniors—who get help with college application coaching—focus on cardiology and community outreach, culminating in a health fair that they organize at their school.

Pipeline is run by Emory student volunteers with the support of the School of Medicine Office of Multicultural Medical Student Affairs, the Office of University-Community Partnerships, and the Emory Center for Science Education.

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Links between autism and epilepsy

An article in the April 2011 issue of Nature Medicine highlights the mechanistic overlap between autism and epilepsy.

By studying how rare genetic conditions known to coincide with both epilepsy and autism—such as Rett syndrome, fragile X syndrome and tuberous sclerosis—unfold at an early age, neuroscientists are finding that both disorders may alter some of the same neural receptors, signaling molecules and proteins involved in the development of brain cell synapses.

Gary Bassell, PhD

Emory cell biologist Gary Bassell and his colleagues have been taking exactly this approach. Recently they published a paper in Journal of Neuroscience, showing that the protein missing in fragile X syndrome, FMRP, regulates expression of an ion channel linked to epilepsy. This could provide a partial explanation for the link between fragile X syndrome and epilepsy.

The Nature Medicine article also mentions a drug strategy, targeting the mTOR pathway, which Bassell’s group has been exploring with fragile X syndrome.

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HIV vaccine design: always a moving target

HIV presents a challenge to vaccine design because it is always changing. If doctors vaccinate people against one variety of virus, will the antibodies they produce stop the virus that they later encounter?

A recently published report on an experimental HIV vaccine’s limited effectiveness in human volunteers illustrates this ongoing puzzle in the HIV vaccine field.

Paul Spearman, now chief research officer for Children’s Healthcare of Atlanta and vice chair for research for Emory’s Department of Pediatrics, began overseeing the study when he was at Vanderbilt. The report is in the April 15 issue of the Journal of Infectious Diseases.

Paul Spearman, MD

The vaccine was designed to elicit both antibody and T cell responses against HIV and in particular, to generate broadly neutralizing antibodies. Unfortunately, it didn’t work. Volunteers who received the vaccine made antibodies that could neutralize the virus in the vaccine, but not related viruses thought to be like what participants in a larger study might encounter.

“High levels of neutralizing antibodies can be raised against HIV, while at the same time, breadth of neutralization has never yet been achieved in a vaccine,” Spearman says. “The essential problem is that the antibodies raised have a narrow specificity, while the virus is extremely variable. In contrast, about 20% of HIV-infected individuals will demonstrate neutralization breadth.”

Last year, scientists demonstrated a method for identifying these broadly neutralizing antibodies in HIV-infected individuals. However, having a vaccine hit that target reliably is still elusive.

Spearman reports that he is in charge of a new trial that will be boosting the same individuals that participated in the previous trial with HIV protein from a clade C virus, starting later this year. Clade C is the predominant HIV subtype in southern Africa, while clade B, used in the published trial, is the predominant subtype in North America and Western Europe.

Posted on by Quinn Eastman in Immunology Leave a comment

Indispensable cilia

Cilia are tiny hair-like structures on the outside of cells. Your memory of cilia may extend back to biology class, when you saw a picture of a paramecium or lung tissues, where cilia keep surfaces free of dirt and mucus.

Ciliated cells in the human oviduct

In the last few years, scientists have been learning more about cilia’s many roles in the body. Nearly all mammalian cells have cilia, and they are thought to act more like antennae, sending and receiving signals. Defects in cilia have been connected to lung, heart, kidney and eye diseases. Accordingly, Emory’s 15th BCMB training grant symposium focuses on cilia, beginning Thursday evening with a keynote talk by Susan Dutcher from Washington University, St. Louis and extending all day Friday.

At Emory, cell biologist Winfield Sale’s laboratory uses the model system of the alga Chlamydomonas to study dynein, a molecular motor that drives the functions of cilia. In addition, geneticist Tamara Caspary’s laboratory is studying how defects in cilia can lead to altered embryonic development. Ping Chen’s group has been examining cilia in the context of inner ear development.

This week’s program is sponsored by Emory’s graduate program in Biochemistry, Cell and Developmental Biology, the Departments of Cell Biology, Biochemistry, Pharmacology, Biology, Microbiology and Immunology, Physics, the Graduate Division of Biological and Biomedical Sciences and the Woodruff Health Sciences Center.

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A milestone in treating hemophilia

Hematologist Pete Lollar has devoted his career to developing treatments for hemophilia A, which is caused by a lack of blood clotting factor VIII. Lollar is a professor of pediatrics in Emory School of Medicine and director of hemostasis research at Children’s Healthcare of Atlanta. Last week, Lollar was honored by Emory’s Office of Technology Transfer for setting in motion research that has progressed to a phase III clinical trial of a new product, OBI-1, a special form of factor VIII.

John "Pete" Lollar, MD

Along with this milestone came a dramatic story, described by OTT’s assistant director Cale Lennon. The first patient to enroll in the clinical trial did so in November 2010 because of what appeared to be acquired hemophilia, which led to severe uncontrolled hemorrhaging. As a result of treatment with OBI-1, developed by Lollar and his research team at Emory, the patient’s bleeding was brought under control and it saved his life. He was treated at Indiana Hemophilia and Thrombosis Center in Indianapolis.

Acquired hemophilia is a challenge for doctors to deal with because it is such a surprise. Unlike people with inherited hemophilia, those with acquired hemophilia do not have a personal or family history of bleeding episodes. Their immune systems are somehow provoked into making antibodies against their own clotting factor VIII. These antibodies also appear over time in about 30 percent of patients with inherited hemophilia who take standard clotting factors.

OBI-1, a special form of clotting factor VIII, is less of a red flag to the immune system. This allows treatment of patients who cannot benefit from standard clotting factor VIII, because of the presence of auto-antibodies.

Emory originally licensed OBI-1 to Octagen Corporation, a “homegrown” startup company founded in 1997. Octagen sublicensed the OBI-1 technology to a French biotechnology firm, Ipsen Biopharm in 1998. Over the next decade, Octagen and Ipsen pursued preclinical and initial clinical studies and completed a phase II clinical trial in 2006. Ipsen purchased the OBI-1 program outright in May 2008.

In January 2010, Ipsen developed a partnership agreement with Inspiration Biopharmaceuticals, which was founded by two businessmen whose children have hemophilia. Under the agreement’s terms, Inspiration licensed OBI-1 from Ipsen and is responsible for its clinical development, regulatory approval and commercialization.

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The next generation of biomedical engineering innovators

Congratulations to the winners of the InVenture innovation competition at Georgia Tech. The competition aired Wednesday night on Georgia Public Broadcasting. The winners get cash prizes, a free patent filing and commercialization service through Georgia Tech’s Office of Technology Transfer.

Several of the teams have Emory connections, through the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory, and the Atlanta Clinical & Translational Science Institute.

Emergency medical professionals know that intubation can be rough. The second place ($10,000) MAID team created a “magnetic assisted intubation device” that helps them place a breathing tube into the trachea in a smoother way. The MAID was designed by Alex Cooper, Shawna Hagen, William Thompson and Elizabeth Flanagan, all biomedical engineering majors. Their clinical advisor was Brian Morse, MD, previously a trauma fellow and now an Emory School of Medicine surgical critical care resident at Grady Memorial Hospital.

“When I first saw the device that the students had developed, I was blown away,” Morse told the Technique newspaper. “It’s probably going to change the way we look at intubation in the next five to 10 years.”

The AutoRhexis team, which won the People’s Choice award ($5,000), invented a device to perform the most difficult step during cataract removal surgery. It was designed by a team of biomedical and mechanical engineering majors: Chris Giardina, Rebeca Bowden, Jorge Baro, Kanitha Kim, Khaled Kashlan and Shane Saunders. They were advised by Tim Johnson, MD, who was an Emory medical student and is now a resident at Columbus Regional Medical Center.

The finalist Proximer team, advised by Emory surgeon Albert Losken, MD, developed a way to detect plastics in the body, which can help breast cancer survivors undergoing reconstruction.

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The Scientist ranks Emory one of top 15 best places to work for postdocs

This year, the readers of The Scientist magazine have ranked Emory University as the 11th best place to work for postdocs in the United States. Among Emory’s strengths, respondents cited training and mentoring, and career development opportunities.

The top U.S. institution was the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts. The top international institution was University College, London. Emory has previously ranked as high as number 4 (in 2006) in The Scientist’s best places to work for postdocs survey.

The ranking was based on responses from 2,881 nontenured life scientists working in academia, industry or noncommercial research institutions. 76 institutions in the United States and 17 international institutions were included.

Emory employs nearly 700 postdoctoral fellows in laboratories in the School of Medicine, Yerkes National Primate Research Center, Emory College, the Graduate School of Arts and Sciences, Rollins School of Public Health and Nell Hodgson Woodruff School of Nursing.

After receiving their PhD degrees, life sciences graduates launch their research careers by working for several years as postdoctoral fellows in the laboratories of established scientists. In addition to engaging in sometimes grueling laboratory research, many postdocs teach, mentor graduate and undergraduate students and apply for their own funding on a limited basis.

 

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One reason why SIV-infected sooty mangabeys can avoid AIDS

Sooty mangabeys are a variety of Old World monkey that can be infected by HIV’s cousin SIV, but do not get AIDS. Emory immunologist and Georgia Research Alliance Eminent Scholar Guido Silvestri, MD, has been a strong advocate for examining non-human primates such as the sooty mangabey, which manage to handle SIV infection without crippling their immune systems. Silvestri is division chief of microbiology and immunology at Yerkes National Primate Research Center.

Research shows sooty mangabeys have T cells that can do the same job as those targeted by SIV, even if they don't have the same molecules on their surfaces

A recent paper in the Journal of Clinical Investigation reveals that sooty mangabeys have T cells that perform the same functions as those targeted by SIV and HIV, but have different clothing.

Silvestri and James Else, the animal resources division chief at Yerkes, are co-authors on the paper, while Donald Sodora at Seattle Biomedical Research Institute is senior author.

One main target for SIV and HIV is the group of T cells with the molecule CD4 on their surfaces. These are the “helper” T cells that keep the immune system humming. Doctors treating people with HIV infections tend to keep an eye on their CD4 T cell counts.

In the paper, the scientists show that sooty mangabeys infected with SIV lose their CD4 T cells, without losing the ability to regulate their immune systems. What’s remarkable here is that sooty mangabeys appear to have “double negative” or DN T cells that can perform the same functions as those lost to SIV infection, even though they don’t have CD4.

CD4 isn’t just decoration for T cells. It’s a part of how they recognize bits of host or pathogen protein in the context of MHC class II (the molecule that “presents” the bits on the outside of target cells). Somehow, the T cells in sooty mangabeys have a way to get around this requirement and still regulate the immune system competently. How they do this is the topic of ongoing research.

The authors write:

It will be important to assess DN T cells in HIV-infected patients, particularly to determine whether these cells are preserved and functional in long-term nonprogressors. These efforts may lead to future immune therapies or vaccine modalities designed to modulate DN T cell function. Indeed, the main lesson we have learned to date from this cohort of SIV-infected CD4-low mangabeys may be that managing immune activation and bolstering the function of nontarget T cells through better vaccines and therapeutics has the potential to contribute to preserved immune function and a nonprogressive outcome in HIV infection even when CD4+ T cell levels become low.

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Emory/Georgia Tech: partners in creating heart valve repair devices

Vinod Thourani, associate professor of cardiac surgery at Emory School of Medicine, along with Jorge Jimenez and Ajit Yoganathan, biomedical engineers at Georgia Tech and Emory, have been teaming up to invent new devices for making heart valve repair easier.

At the Georgia Bio and Atlanta Clinical and Translational Science Institute’s second annual conference on academic/industry partnerships, Thourani described how he and his colleagues developed technology that is now being commercialized.

Apica Cardiovascular co-founders (l-r) James Greene, Vinod Thourani, Jorge Jimenez and Ajit Yoganathan

Apica Cardiovascular was founded based on technology invented by Jimenez, Thourani, Yoganathan and Thomas Vassiliades, a former Emory surgeon.

Thourani is associate director of the Structural Heart Program at Emory.

Yoganathan is director of the Cardiovascular Fluid Mechanics Laboratory at Georgia Tech and the Center for Innovative Cardiovascular Technologies.

The technology simplifies and standardizes a technique for accessing the heart via the apex, the tip of the heart’s cone pointing down and to the left. This allows a surgeon to enter the heart, deliver devices such as heart valves or left ventricular assist devices, and get out again, all without loss of blood or sutures.

Schematic of transapical aortic valve implantation. The prosthesis is implanted within the native annulus by balloon inflation.

At the conference, Thourani recalled that the idea for the device came when he described a particularly difficult surgical case to Jimenez.  Thourani said that a principal motivation for the device came for the need to prevent bleeding after the valve repair procedure is completed.

With research and development support from the Coulter Foundation Translational Research Program and the Georgia Research Alliance VentureLab program, the company has already completed a series of pre-clinical studies to test the functionality of their device and its biocompatibility.

Posted on by Quinn Eastman in Heart Leave a comment