This piece was written in May 2017, soon after the Wharton Neuroscience Initiative launched.
By Lauren Hertzler
At first, business and neuroscience might seem like an improbable pair. So when Penn launched its Wharton Neuroscience Initiative, WiN for short, its distinctiveness spurred particular attention: How exactly do the two fields coincide?
“It’s shocking and provocative,” says Michael Platt, the program’s founding director. “But that’s exactly what we aim to be. The Wharton Neuroscience Initiative is a deliberate mash-up of neuroscience and business, and our intention is to explore every domain in which these two can inform each other.”
WiN launched this past September, and opened its bright, new space in Steinberg-Dietrich Hall—right next to the Wharton Behavioral Lab—just before winter break.
It’s led by Platt, a Penn Integrates Knowledge professor with appointments in the departments of Neuroscience, Psychology, and Marketing, and Elizabeth Johnson, WiN’s executive director and senior fellow. The duo worked for more than a decade together at Duke University before coming to Penn last year. Kate Molt, who formerly worked in Wharton’s marketing department, serves as the program’s coordinator.
“Wharton is not your grandfather’s school of finance anymore,” Platt says. “Just as it has put major investments into analytics and innovation, Wharton knows neuroscience will be key to the practice in the next decade.”
The relationship often comes down to decisionmaking—something the business community spends a lot of time thinking about.
“But we know relatively little about the biological mechanisms that underlie decision-making,” says Johnson, a neuroscientist by training. “Although there have been great strides made in the last 15 years in that capacity, it hasn’t moved into the realm of application yet.”
Platt continues, “We are finally in a position to apply that knowledge in a much more real-world environment, to real-world questions that have impact. What was a dream 20 years ago can now be achieved.”
WiN’s goal isn’t to turn Wharton students into neuroscientists. It’s more about developing a common language.
“You have to have a lingua franca in order to even begin to have creative applications emerging out of this community,” Johnson says. “You have to have a sense of open communication between disciplines, which this forum provides.”
Some early faculty affiliates include the Annenberg School for Communication’s Emily Falk, whose work predicts behavior change after exposure to persuasive messages; the Wharton School’s Gideon Nave, who studies the biological basis for how humans make decisions; the School of Engineering and Applied Science’s Danielle Bassett, who uses tools from network science and complex systems theory to enhance understanding of connectivity in the brain; and the School of Arts & Sciences’ Coren Apicella, who analyzes the evolutionary origins of social behaviors.
The Initiative hopes to “amplify” the academic homes of its faculty members, as well as students, Johnson says.
“I think situating this kind of initiative at a university where it’s a walking campus in an urban landscape, where the schools of medicine, law, business, arts and sciences, even vet, are all right here, is an incredible asset,” she says. “It encourages movement into an intellectual space like Wharton, where they may not have felt was their home before.”
As WiN continues to develop its presence on campus, it hopes to be a place for related education—it’s already spearheading new courses—and abundant research opportunities.
“We hope to bolster the educational and research platform to make it possible to do integrative research that’s both vertical and horizontal,” Johnson explains. “By vertical I mean undergraduates all the way through faculty, but even more vertical to include outside partners from industry and the corporate world, and by horizontal I mean from across many different disciplines.”
A big part of WiN’s plans is also to sponsor regular, open-to-the-public events. It’s already coordinated a half-day conference this past December, focused on the interactions between brain science and marketing.
“Philadelphia is such a hub of activity for us, and we want to engage with the community at large,” Johnson says. “It will only increase what we are capable of doing.”
Lauren Hertzler is a staff writer for Penn Today published by University Communications.
By Hannah Kleckner, Penn Vet
Gaunt, stuporous zombie-like deer are stumbling through the American wilderness. Not a product of Hollywood’s imagination, these animals are a very real concern for public health and wildlife officials.
Across the U.S., a growing number of deer are testing positive for chronic wasting disease (CWD), one in a family of rare neurodegenerative diseases that affect humans and animals. Known as prion diseases or transmissible spongiform encephalopathies (TSEs), they include bovine spongiform encephalopathy (BSE), commonly called mad cow disease, Creutzfeldt-Jakob Disease (CJD), variant CJD (vCJD), and more. Symptoms mimic the behaviors of pop culture’s favorite monsters and include extreme thirst and salivation, ataxia, and listlessness, among others.
The diseases are similar and stem from aberrant prion proteins that spark a sponge-like deterioration of the brain. (Penn alumnus Stanley B. Prusiner, C’64 and M‘68, earned the 1997 Nobel Prize for Medicine for discovering prions.)
“The prion protein naturally occurs in animals,” said Perry Habecker, chief of large animal pathology at Penn Vet’s New Bolton Center, which conducts immunohistochemistry tests for CWD and scrapie, another prion disease that affects sheep and goats.
A normal prion is made by cells, consumed by cells, and transported in the body. It never accumulates. “In prion diseases, an abnormal prion sets off a cascade of events when the normal prion has a conformational change,” shared Habecker. “All prions then stick together, and the body cannot get rid of them. The proteins just build up until the buildup translates into a neurological dysfunction of wasting, stupor, and, ultimately, death.”
Death from prion diseases is certain—once the cascade starts, nothing can stop it.
“Prions are the first ‘infectious agent’ that don’t have DNA in them,” said Habecker. “We know about viruses, bacteria, protozoa, fungi, but prions can infect and cause disease and not really reproduce themselves in a way that a bacteria, fungus, protozoa, or virus would with DNA. So, we don’t have a way to stop or reverse the diseases.”
Species to Species to Species
Therein lies the fear of widespread, uncontainable prion outbreaks. There is no known treatment for humans or animals. And prion diseases are, in some cases, transferrable among species.
Many of us remember the outbreak of mad cow disease in the United Kingdom for its impact on the cattle industry and threat to human life. At the epidemic’s peak in Britain, almost 1,000 cases were reported each week and eventually totaled in the death of nearly 180,000 cattle from 1986-2001.
The outbreak also claimed human lives. Since 1996, 231 people in 12 countries, including the UK, France, the U.S., and Canada, have died from its variant, vCJD. It’s widely believed humans contract vCJD from eating meat from cattle infected by mad cow disease.
And while national occurrences of CJD have increased from 260 to 481 cases between 2002-2015, the Centers for Disease Control and Prevention (CDC) is not linking CJD to CWD or any other animal-originated prion diseases.
Zombie Deer Are Here
Mad cow disease is no longer an imminent public health issue; scrapie, according to Habecker, is “pretty much under control;” and kuru, another human-form prion disease, has essentially been eradicated. But CWD weighs on the minds of hunters, deer farmers, wildlife experts, and public health officials.
As of January 2018, the disease had been detected in free-ranging and captive deer and elk in 22 states and two Canadian provinces.
“CWD originated from captive deer in Colorado,” explained Habecker. It was first recognized in the 1960s. “Over the years, deer breeders shuffled infected deer between farms and hunting preserves, redistributing the disease throughout the country.”
Perry Habecker of Penn Vet’s New Bolton Center helps lead a surveillance program that includes tests for the prion-transmitted infection chronic wasting disease.
In 2012, CWD made its first showing in Pennsylvania at a captive deer facility. This year, the number of infected deer is large enough that the Pennsylvania Game Commission has designated four parts of the state as Disease Management Areas. Hunting, feeding, and transporting deer is restricted in these areas. And samples of brain or spinal cord tissues is tested from every deer killed by hunters, as well as from road kill and deer culled by the Game Commission.
Although some evidence exists that CWD has zoonotic potential, “as far as we know it is not a threat to humans” said Habecker. He referenced tests in squirrel monkeys and macaques. Researchers found squirrel monkeys inoculated with brain tissue from a CWD infected deer acquired the disease.
Macaques, evolutionarily closer to humans than squirrel monkeys, were found unsusceptible in one study but susceptible in another. Researchers are also currently exploring whether the disease transplants from deer to plant life—and if so what the implications are.
Penn Vet on the Frontline
On the frontline of CWD, Penn Vet tests non-captive, hunter-killed deer in Pennsylvania. Additionally, it tests deer for several Northeastern states. Habecker screens nearly 1,000 samples a year with technology called an Autostainer that examines about 200 specimens at a time.
With the School’s services for the Pennsylvania Animal Diagnostic Laboratory System, a partnership among Penn Vet, the Pennsylvania Department of Agriculture, and Penn State University, the pathology team also keeps a close watch for other emerging threats to animals and food sources.
Penn Vet faculty not only provide vital diagnostic information, they contribute to the control and eradication of infectious diseases. For example, New Bolton Center was instrumental in developing an avian flu surveillance program after a 1983-84 avian flu outbreak necessitated the death of more than 17 million birds. In the last two subsequent outbreaks of avian flu alone, Penn Vet was instrumental in preventing nearly $5 billion in damages.
As a monitor of CWD, Habecker is concerned, although he’s not ready yet to raise a red flag. “We haven’t reached a tipping point, though we are monitoring the situation closely.”
Even if experts are not linking upticks of human prion diseases to a rise in CWD in deer, research demonstrating the transmission of the disease from venison to monkeys has heightened the CDC’s attention. The agency continues to watch for human CWD, investigating unusual cases of human prion disease and cases in people with increased risk of exposure to chronic wasting disease.
For the foreseeable future, however, Habecker advised, “When neighbors bring a gift of venison they’ve killed, go ahead and eat it. If they’re eating it, you’re probably safe to eat it too.” You will not, he reassured, join the walking dead.
Hannah is the communications specialist for Penn Vet’s New Bolton Center.
Nanotechnology is enabling new materials and devices that work at sizes so small that individual atoms and molecules make a difference in their behavior. The field is moving so fast, however, that scientists from other disciplines can have a hard time using the fruits of this research without becoming nanotechnologists themselves.
With that kind of technology transfer in mind, the University of Pennsylvania’s Center for Targeted Therapeutics and Translational Nanomedicine has established the Chemical and Nanoparticle Synthesis Core.
Supported by the Perelman School of Medicine and its Institute for Translational Medicine and Therapeutics, the School of Engineering and Applied Science, and the School of Arts & Sciences’ Department of Chemistry, this core facility aims to help Penn researchers design and synthesize custom molecules and nanoscale particles that would be otherwise hard to come by.
“Based on a short survey we conducted, we found that many faculty members want to synthesize unique chemical compounds, such as imaging agents, drugs or nanoparticles, but they don’t have the expertise to produce these compounds themselves,” says Andrew Tsourkas, professor in Penn Engineering’s Department of Bioengineering and Director of the Chemical and Nanoparticle Synthesis Core. “As a result, these projects are often abandoned.”
Claire Mitchell, professor in the School of Dental Medicine’s Department of Anatomy & Cell Biology and the Perelman School of Medicine’s Department of Physiology, knows this story all too well. As one of the Core Facility’s first users, she’s restarting neuroscience research that had been long stymied by a lack of access to nanotech expertise.
Six years ago, Mitchell began a research project that investigated the role of the lysosomes on aging-related diseases, such as macular degeneration and Alzheimer’s. The organelles responsible for degrading cellular waste, lysosomes become less acidic as people and their cells age, and thus less capable of breaking down this waste.
Mitchell collaborated with a colleague at the University of Colorado, who developed nanoparticles that lysosomes would ingest. The nanoparticles help the lysosomes acidify, which leads to the more efficient degradation of cellular waste. They published preliminary findings that suggested that preventing the accumulation of these waste products may help prevent early signs of macular degeneration in retinal cells.
Mitchell’s next target was neurons; while getting the nanoparticles to a patient’s brain would be an additional challenge, she hypothesized that in vitro studies that would show their pH-lowering effect would offer a new therapeutic approach for the treatment of Alzheimer’s.
However, after Mitchell’s initial supply of nanoparticles ran out, she was unable to procure any more.
“My colleagues and I have tried a dozen or more potential research collaborators, but for synthetic chemists, our nanoparticles just aren’t very interesting on their own,” Mitchell says. “While we recognized their considerable potential, the relative simplicity of these nanoparticles made them less interesting for the chemists; they weren’t worth their time or effort to make.”
The nanoparticles in question are simply microscopic balls of polylactic acid (PLA), a plastic that is commonly used as a medium for 3D printing. The trick was getting them to the exact diameter necessary for Mitchell’s experiments: 300 nanometers.
A uniform size is key, as it allows the nanoparticles to enter the lysosomes and reduces off-target effects. While Mitchell and her lab members had access to the equipment and materials to make PLA nanoparticles, they needed professional help to achieve the necessary level of precision.
“We tried to make these nanoparticles ourselves, but we’re not chemical synthesis experts,” Mitchell says. “The Core Facility is a dream come true. Not having to reinvent the wheel allows us to focus on our neuroscience and the prevention of age-dependent damage to the cells.”
Mitchell’s forthcoming experiments with the PLA nanoparticles will investigate the link between microglial cells and the amyloid plaques that are a hallmark of Alzheimer’s. Microglial cells are the primary phagocytes of the brain; she and her colleagues hypothesize that acidifying their lysosomes will improve their ability to clear these plaques.
“Once we’re back to where we were six years ago, there’s huge opportunities to tweak these nanoparticles for new experiments,” Mitchell says. “There are lots of ways we can improve the nanoparticles’ design to enhance and improve this approach. The whole lab is excited that the Core will help us finally make these nanoparticles. It’s a great lesson to never give up.”
Image: Nanoparticles enhanced the degradation of cellular waste in light-sensing retinal cells, according to research by Penn Dental Medicine’s Claire Mitchell, an activity that may help prevent early signs of macular degeneration. (Image Courtesy of PLOS One)
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Beginning today and continuing throughout April, we will be featuring stories about research and care related to the brain, behavior, and neuroscience. Keep track of the news here, use the hashtag #pennonehealth to share it, and let us know what you think at email@example.com. Thanks for reading!
By Katie Delach, Penn Medicine
Sticks and stones may break your bones, but modern medicine usually helps you get back to normal quickly. Though fractures and other injuries may case aches and pains and damaged ligaments and joints may never be exactly the same as they once were, the scars left by a traumatic brain injury (TBI) often manifest in less visible ways; ways that researchers and clinicians have only just begun to really understand.
“Injuries that cause visible physical disabilities—those that may result in paralysis, or the need for casts and wheelchairs—were long considered to be ‘diseases of the body,’ and diseases that result in disabilities such as personality changes, mood disorders, anxiety, insomnia, addiction, and trouble with memory and attention, were thought of as ‘diseases of the soul.’ But that’s changed,” says Ramon Diaz-Arrastia, associate director for Clinical Research in Penn’s Center for Neurodegeneration and Repair, the presidential professor of Neurology, and the director of the Traumatic Brain Injury Clinical Research Initiative at Penn Medicine. “We know now that brain injuries are not an injury of the soul. A traumatic brain injury (TBI) is a disease of the body—it affects the whole nervous system. The brain is a complex organ, and even though we can’t see its scars in the same way we can see them from other injuries, they are certainly there long after a patient has been treated and ‘recovered.’”
According to the CDC, in the United States alone, an estimated 2.5 million people sustain a TBI each year, and of them, 52,000 die and 280,000 are hospitalized. More than 2.2 million are treated and released from an emergency department, but the impact of a TBI can last well beyond a hospital visit, and without proper attention and care, can change the course of a person’s life.
It’s been 19 years since Amy Kraft’s brain injury and in some ways, she’s still recovering. Kraft, 35, was heading to a coffee shop with some friends after rehearsal for a school play when she was accidentally hit by a car. She was a sophomore in high school, a good student with a solid core group of friends, plans to attend college, and aspirations of being a journalist.
“I don’t remember anything from that day,” says Kraft, who is not a patient of Diaz-Arrastia’s but has become a strong advocate and resource for those with TBIs in the years following her injury, and will be participating in Penn Medicine’s Mind Your Brain conference this month. “The doctors told my parents if I didn’t come out of my coma within a week, it was likely that I would have serious brain damage. I woke up on day six. The first thing I remember is sucking water from a washcloth and seeing my grandmother standing at the foot of my hospital bed.”
In addition to her brain injury, Kraft also suffered a ruptured spleen, broken clavicle, broken ribs, broken femur and humerus, and a host of other injuries. When she was well enough, a neuropsychological exam revealed difficulty with short-term memory, problem-solving skills, and speech, and her math and reading skills were reduced to that of a sixth grader. But, in truth, the worst was yet to come, and there was no test anyone could give her that could predict it.
“I didn’t have any emotional issues at first. I was pretty calm and accepting of the whole thing, and just wanted to get out of rehab and get back to my friends and my life,” Kraft says, adding that she did her rehab exercises practically around the clock for nearly a month in an effort to try and speed her recovery. “Once my hair started growing, I started walking, my short-term memory came back…I looked fine, so nobody thought there could be something else going on.”
Little did she know then that it was only when she tried to go back to her life that the true extent of her injuries would be realized. Diaz-Arrastia says that some TBI patients make full mental and physical recoveries from their injuries and do not experience cognitive issues, but for a large number, the recovery may be only physical, and acclimating to daily life can be difficult.
“I suddenly just didn’t feel like I fit in. I was overwhelmed with feelings of inadequacy. I didn’t know how to fit in, and I didn’t know how to socialize,” Kraft explains. It wasn’t long before she turned to drugs and alcohol for relief. “I got into a bad place very quickly.” By the time she was 17, Kraft was “a black-out drinker,” and by the time she was 18, she was homeless and living out of her car.
Part of the problem, Kraft says, was she couldn’t understand what was happening to her. Her family, she says, couldn’t explain or understand the sudden changes in her behavior and didn’t know where to turn for help.
“For a lot of reasons it wasn’t uncommon 10 or 15 years ago for TBI patients to be sent home with zero follow-up, and zero resources or attention,” Diaz-Arrastia says. “Patients would come for follow-up care on their other injuries with specialists in orthopedics or trauma, but three or six months later those injuries were largely healed and almost all of the disability was related to the brain injury. Care that’s targeted at the TBI is certainly getting better, but it continues to be an unmet need.”
Recognizing the unmet need and the immense number of patients who could benefit from support services, Diaz-Arrastia has spent the past 18 months pulling together a team of clinical specialists who are focused specifically on these vulnerable and often overlooked families.
“Clinical care for TBIs has come a long way, but it’s still behind other neurological subspecialties,” says Megan Moyer, a nurse practitioner in neurology who heads up Penn’s TBI support group for patients and family members. “With a paucity of specialists focusing on these injuries, patients often are lost in the shuffle of the system, going to primary care for follow-ups, or seeing specialists only for other injuries that aren’t related to the TBI.”
Penn’s TBI support group started six months ago and, in that short time, has seen remarkable growth with patients and their family members attending meetings for the education as much as the support and knowledge that they aren’t alone.
Despite not having access to the resources, Amy Kraft was one of the lucky ones. When she realized that she was going to die if she didn’t make major changes, she took her first steps toward rehab—both for her substance abuse and her TBI. Today, she’s been sober for 16 years and was even able to still realize her dreams of becoming a journalist.
Still, even after getting clean, Kraft says she dealt with anxiety and insomnia for years. It wasn’t until a therapist suggested some of her struggles could be related to her TBI and started addressing it head on that her symptoms began to subside.
It’s a realization Moyer says she hears often from Penn patients.
“Patients who’ve experienced traumatic brain injuries and their family members need a place to go where they can realize they aren’t crazy, and they aren’t alone,” Moyer says. “We hear a lot of patients say they just didn’t know that a TBI could cause changes in mood or behavior or insomnia. So, for them, just being able to point to something and say ‘ah-ha, that’s why this is happening to me,’ makes a world of difference.”
Top photo: Amy Kraft and her family. Inset photo: Kraft recovering after a traumatic brain injury from a car accident. (Courtesy: Amy Kraft)