The University’s annual science symposium brought together noted researchers and scholars from across the University and around the world for a series of lectures and panel discussions in addition to a technology showcase, poster sessions and “Science as Art” display of microscopy images.

This year’s symposium, “Science 2015 Unleashed!” took place Oct. 7-9 in Alumni Hall.

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Vet medicine + environment aid understanding of human health

The idea that veterinary medicine and environmental conditions add to the understanding of human health is at the core of One Health, a collaborative initiative of faculty from Pitt’s Schools of the Health Sciences and the University of Pennsylvania School of Veterinary Medicine that made its debut at an Oct. 9 session of Science 2015.

Donald S. Burke, dean of the Graduate School of Public Health, who is researching zoonotic diseases — those originating in animals and insects — noted that many diseases are transmitted at various stages from animals to humans, including HIV, SARS, West Nile virus, encephalitis, Asian influenzas, Ebola, rabies, Lyme disease and salmonella.

About eight years ago, Burke said, scientists from Pitt and elsewhere began discussing the need to bring together veterinary and human medicine, forming the first One Health advisory board in 2010, which today includes four members from Pitt or western Pennsylvania. The effort is spearheaded by Arthur Levine, John and Gertrude Petersen Dean of the School of Medicine and senior vice chancellor for the Health Sciences.

Joan C. Hendricks, the Gilbert S. Kahn Dean of Penn’s veterinary medicine school, or PennVet, noted that Penn’s medical school was founded by Benjamin Rush, one of the signers of the Declaration of Independence, who made a prescient speech in the early 19th century about the connection between animal and human health. He asserted that animal and human bodies, and the medicines that treat them, worked similarly. “How did he know?” Hendricks said. “But it is all true.”

PennVet was founded in 1884 in West Philadelphia as a rare veterinary school in an urban setting, situated nearer family pets and the country’s major consumers of food.

Hendricks pointed out that animals and humans share illnesses, such as cancer and heart disease, and that studies of vaccines and the microorganisms in animals that either kill them or keep them alive have long connected veterinary research to progress in treating and preventing human ailments.

She spoke about her own journey into academic medicine as an exemplar for One Health careers.

As part of Science 2015, Karl Deisseroth, the D. H. Chen Professor of Bioengineering and of Psychiatry and Behavioral Sciences at Stanford, delivered the Dickson Prize in Medicine Lecture Oct. 8. He spoke on “Optical and Chemical Tools for High Resolution Investigation of Intact Biological Systems.”

Graduating from Penn’s VMD/PhD program in 1980, she began research focusing on sleep, trying to determine how the characteristics of sleep connected to waking behaviors. Scientists still don’t know how to re-create natural sleep in laboratory animals, she said. “We don’t even know why we sleep,” Hendricks added, although “we clearly must do it.” The need to save and regain bodily energy by staying immobile each night is one fairly obvious benefit of sleep, she said, but it is still not entirely clear what benefits we derive from unconsciousness.

The main question she faced as someone working at the intersection of animal and human health  was, “What clinically relevant research were you going to do with your training?”

She started with cats, which are useful models for sleep research, since they sleep 80 percent of the time both in and out of the lab. Then she switched to bulldogs, which all suffer from sleep apnea (compared to  5 percent of humans), due to their short, flat faces, akin to the shape of human faces, which results in upper respiratory obstructions.

Then Hendricks moved to fruit flies, which she called “essentially the genetics model organism” for human-relevant research. Fruit flies have a sleep-like state, she said; they groom themselves prior to sleeping, and “they sometimes get up and have a midnight snack.” They may be simple organisms, but they allow researchers to identify molecular pathways that are relevant for research, and their use presents few ethical dilemmas or regulatory burdens for scientists. The result has been numerous papers detailing molecular pathways that link sleep to bodily conservation and the relationship of sleep to learning and behaviors.

All of this “bench to bedside” work — Hendricks prefers “lab to Labrador” — above the evolutionary level of fruit flies has its difficulties, she allowed. Lab animals provide researchers with evolutionary and comparative insights but sometimes have questionable relevance to humans, and their treatment creates ethical and regulatory responsibilities for researchers.

Instead, she said, scientists ought to look at veterinarians’ animal patients with naturally acquired diseases, since their conditions are more highly relevant to the human experience of disease than that of animals with diseases created in laboratory settings. “We think animal patients have more in common with human patients than normal animals in a lab do,” she said.

Hendricks, noting that Pennsylvania has a large agricultural industry and the largest non-farming rural population in the United States, hopes that Pitt and PennVet’s collaborations will grow, and that by the end of 2016, “People will know that Pennsylvania is the One Health commonwealth.”

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Other researchers showcased work that relates investigations on animals to eventual human health improvements. Simon M. Barratt-Boyes, a faculty member in Pitt’s public health school, began his career as a horse veterinarian in New Zealand and now is examining the applicability of non-primate models of HIV/AIDS and influenza in humans.

Nathan Clark, a faculty member in computational and systems biology in the School of Medicine, is studying the evolution of marine mammals to find genetic convergence, which is leading to research on genetic diseases in humans.

Clark notes that diversity in the phenotypes of mammals shows most obviously in their differing adaptations to habitats, and in their strategies for survival: flying or swimming, using vision or echo location to navigate, in the cold or in the heat. What genetic changes have allowed similar adaptations to singular environments, such as our oceans?

Today, with full genome sequences available for all mammal species, Clark and his colleagues are able to study the main influences on genetic convergence, starting with the forces that govern the very conservation of each species and its genes. This force can fluctuate in usefulness to each species over time, and can cease functioning if a certain gene and its expressed trait stop being useful. Other forces at work include adaptation to environmental or other challenges and coevolution with other creatures, such as viruses.

Despite the fact that marine mammals do not all come from the same species, and that some, such as dolphins, manatees and others, returned to water from land during their evolution, Clark’s lab found gene-trait correlation among them. All have developed genes that make them streamlined, with reduced limbs. “Basically, all marine species have lost their sense of taste,” he added, and have undergone similar epidermal and lung changes that make their skins less permeable to water and protect them from the large pathogen load contained in their saltwater environment.

Marine species tend to converge genetically a lot more than do land animals, but Clark has also studied subterranean mammals, including three animals that went underground as a species after living for a period above ground. All of them have “mole” in their names, although they are not related species.

Not surprisingly, he has found convergence among the changes in the genes that govern their visual functions. Although this was an expected conclusion, the fact that it has been borne out by genetic studies was “a nice sanity check” for this type of research, he said.

As a result, he has begun research to see if these genes are related to genes that cause human diseases of the eye, teaming with Eye and Ear Institute. He also plans to look at genes related to the regulation of body traits and longevity, since mammalian phylogeny has a huge range and longevity is correlated to body size.

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William A. Beltran, an ophthalmology faculty member at PennVet, is studying retinitis pigmentosa in animals and humans.

One in 3,500 people has this impairment due to a genetic mutation that can be carried by 238 genes. It is an inherited, progressive degeneration that affects the eye’s rods primarily, but also the cones. There is no treatment and no cure.

At first, retinitis pigmentosa patients have trouble seeing under dim light, then their field of vision begins to shrink from the outside in, causing tunnel vision as cones die on the periphery of the eye. It usually starts before age 10, causing legal blindness by age 45.

More than 100 breeds of dog have progressive retinal atrophy, the canine equivalent of retinitis pigmentosa, with 18 genes in dogs identified so far as its cause. Beltran’s canine research has looked at the eye’s receptor cells and the outer nuclear layer. In 2001, he identified the first dog genetic therapy that was effective on progressive retinal atrophy.

His research initially proved that, in dogs, early disease onset or early progression of the disease could be halted. But could the canine therapy work in humans, whose disease may not be caught as early? Would doctors be able to intervene after human patients are first diagnosed?

So Beltran looked again at canine eye disease, testing whether his therapy would help their eyes both structurally and functionally at later stages of the disease, and found that it did. Now, he said, “we can expand this window of opportunity for therapy to patient-relevant stages of disease.”

—Marty Levine