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UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE | SUMMER 2007PITTMED“PLAIN PEOPLE,”COMPLEX CURESA BETTER LIFE FOR THEIR CHILDRENSOMETIMES MEANS TRANSPLANTS

OVER THE TRANSOMSOUTH BY SOUTHWESTWhat could be better than the University of Pittsburgh Winter Academy in Naples, Fla.?How about two winter academies? To reach even more alumni, we’ve added one in Phoenix, Ariz.In only two years, the University of Pittsburgh Winter Academy has grown to become a premierevent showcasing Pitt’s world leadership in research shaping tomorrow’s health care. Make plansnow to attend—February 2008 in Naples or March 2008 in Phoenix.For more information, please contact Pat Carver, director of alumni relations for the healthsciences schools, at cpat@pitt.edu or 412-647-5307.We gladly receive letters (which wemay edit for length, style, and clarity).Pitt Med400 Craig HallUniversity of PittsburghPittsburgh, PA 15260Phone: 412-624-4152Fax: 412-624-1021E-mail: medmag@pitt.eduhttp://pittmed.health.pitt.eduFor address corrections:Pitt Med Address CorrectionM-200k Scaife HallUniversity of PittsburghPittsburgh, PA 15261E-mail: medalum@medschool.pitt.eduRECENTMAGAZINE HONORSAAMC Publications ExcellenceAAMC Robert G. Fenley WritingAward of Excellence(C. Staresinic’s “Only Starzl Dared To”)AAMC Robert G. Fenley WritingAward of Distinction(J. Miksch’s “Hidden Connections”)IABC Golden Triangle Award of ExcellenceBook and Magazine Cover DesignIABC Golden Triangle Award of HonorMagazine DesignIABC Golden Triangle Award of HonorFeature WritingCASE District II AccoladesGold, Periodical Staff Writing

PITTMEDUNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE MAGAZINE, SUMMER 2007 (MAY/JUNE/JULY)VOL. 9, ISSUE 2DEPARTMENTSOF NOTE 3Pancreatic cancer’s genetic helper.Stress and a sweet tooth.Rickets may be back.CLOSER 7At 17, it was about time she gota research gig at Cal Tech.INVESTIGATIONS 8Ubiquitin—it’s everywhere!What do you feed trauma patientswho can’t feed themselves?MATCH RESULTS 33Coming to a hospital near you.ATTENDING 34Science and murder.ALUMNI NEWS 36David Sherwood has seensome real cliffhangers.A cancer drug that kills cancer too fast.LAST CALL 40Frankenstein’s 190th birthday.18FEATURES“Plain People,” Complex Cures 12The Amish and Mennonites are highly susceptible to inherited metabolicdisorders. At the Clinic for Special Children near Lancaster, Pa., doctorsrefer all patients in need of curative transplants to Pitt.COVER STORY/PHOTO-ESSAY BY CAMI MESATEXT BY JOE MIKSCHCONTRIBUTORSAfter high school, CAMI MESA [“‘Plain People,’ Complex Cures”] was less than certain abouther career path. A native of Colombia living in California, she enrolled in the Art Center College ofDesign in Pasadena. There, she picked up a camera and became enchanted: “I love to play with mycomposition, how it is working in the frame of my camera and how the lighting is hitting the subject.But more than anything, I try to find a connection between the person and myself.” Mesa saysher trip to Amish Country for Pitt Med let her exercise what she calls her strength—portraiture. Andshe relished the human side of the assignment. “I wasn’t sure what to expect, but at the end of theday, all I could feel was an incredible community that comes together for each other,” she says.MELINDA WENNER [“Telltale Hearts, and Veins”] is a Brooklyn-residing native of Denmark whoearned a bachelor’s degree in music composition from the University of Michigan. With that diplomain hand, she embarked on a writing career and has since seen her work published in ScientificAmerican Mind, SEED, The Boston Globe, and The Scientist. (Oh, she also has a bachelor’s degreein cell and molecular biology from Michigan and a master’s degree from New York University’s science,health, and environmental reporting program.) While working on “Telltale Hearts,” Wennersays she found herself moved by the patients’ stories: “[They] were inspiring. They have incrediblypositive outlooks on life.”COVERRCommunities that normally eschew technology turn to transplants to cure their children.(Cover: Cami Mesa © 2007.)The Modern Deathbed 18The modern death ritual centers around the pounding of chests andother heroic measures. But that’s not what we say we want. Where dodoctors fall short of offering “the good death”?BY ELAINE VITONEDefining Moments 24Four Class of ’62 standouts look back on 45 years of discovery.INTERVIEW BY SHARON TREGASKISTelltale Hearts, and Veins 28Synthetic cardiac tissue is a design conundrum, but Pitt bioengineersare attracting attention with their prospective solutions.BY MELINDA WENNER

DEAN’S MESSAGEPITTMEDPUBLISHERArthur S. Levine, MDEDITOR IN CHIEFErica LloydART DIRECTORElena Gialamas CerriSENIOR EDITORChuck StaresinicASSOCIATE EDITORJoe MikschPRODUCTION COORDINATORChuck DinsmoreSTAFF CONTRIBUTOREmily KaramOBITUARIES CONTRIBUTORMacy Levine, MD ’43CIRCULATION MANAGERCrystal KubicCHIEF EDITORIAL ADVISORKenneth S. McCarty Jr., MD, PhDEDITORIAL ADVISORSEdward Barksdale Jr., MDPaula Davis, MASusan Dunmire, MD ’85, Res ’88Jonathon Erlen, PhDJoan Harvey, MDJohn Horn, PhDSteven Kanter, MDJoan Lakoski, PhDDavid Lewis, MDMargaret C. McDonald, PhDRoss Musgrave, MD ’43David Perlmutter, MDKevin Proctor, Class of ’09Gabriel Silverman, Class of ’09Peter Strick, PhDGerard Vockley, MD, PhDSimon Watkins, PhDMarshall Webster, MD, Res ’70Julius Youngner, PhDOFFICE OF PUBLIC AFFAIRSRobert HillJohn D. Harvith, JDBeauty is unbearable, drives us todespair, offering us for a minutethe glimpse of an eternity thatwe should like to stretch out overthe whole of time.—Albert CamusIn this issue of the magazine, a writer exploreshow physicians may fail to interact effectively withterminally ill patients and their families (“TheModern Deathbed,” p. 18). I know from my ownexperience as an oncologist how difficult it can be to relate squarely with families whoare desperate for miracles. For instance, imagine how flummoxed a young doctor couldbecome if a dying patient asked, “Just between you and me, Doc, we’re going to kick thisthing, right?” So why don’t doctors handle these situations more skillfully?The question makes me think of a talk Fadi Lakkis gave recently. Dr. Lakkis is the scientificdirector of the Thomas E. Starzl Transplantation Institute. He noted that, in the lab,sponges retrieved from the deep sea can be induced to fuse together into one organism ifthey are genetically identical. If they are genetically distinct, however, they repel one another(“innate immunity”). For 800 million years, this primitive ability to recognize “nonself”has been vital to the sponge’s self-preservation. The ability is critical to the most basic ofbiological needs—to reproduce one’s genes and thereby to sustain one’s “identity.” Fusingwith another organism—even one of the same species—would permit the possibility thatthe organism might pass on the genes of another invading organism, diluting or even extinguishingthe very identity that might otherwise offer a “glimpse of eternity.”The immunology of sponges may seem leagues away from what takes place in our discussionsin the ICU. Yet I submit that our instinct for preserving our identity is likewiseconserved by millions of years of evolution. Moreover, as the renowned social anthropologistErnest Becker has written, “the wellspring of all human activity is the fear of dying.”Absent our sense of these profundities, we cannot care for our patients with wisdom.When we see our patients dying, we must confront our own mortality. At the NationalCancer Institute, where I was an attending physician years ago, oncology fellows admitted,after some prodding, that they avoided their dying patients. Sometimes they unknowinglyidentified with them. Sometimes they were angry with them. The last thing young doctorswanted to do was to enter into meaningful discussions with terminally ill patients and theirfamilies that would stray from the reporting of medical facts—discussions that might touchon a parent’s guilt or a patient’s fear, for example.But, as those oncology fellows learned, when physicians don’t run from their patientsand instead come to see a patient’s experience as a guide to confronting their own mortality,the rewards are profound. We come to know our patients and ourselves at a deeperlevel, and we become better doctors.Camus also said, “It is normal to give away a little of one’s life in order not to lose it all.”JULIA MAROUS STRAUTPitt Med is published by the Office of the Dean and Senior ViceChancellor for the Health Sciences in cooperation with the alumniand public affairs offices. It is produced quarterly for alumni, students,staff, faculty, and friends of the School of Medicine. PR 5998The University of Pittsburgh is an affirmative action, equalopportunity institution. © 2007, University of PittsburghArthur S. Levine, MDSenior Vice Chancellor for the Health SciencesDean, School of Medicine2 PITTMED

OF NOTEDevoted to noteworthyhappenings in the medicalschool ... To stay abreast ofschool news day by day, seewww.health.pitt.edu.Love in Springtime?Pitt researchers have discovered that women who conceive in springtime are at ahigher risk of delivering children prematurely. Women conceiving in summer have thelowest rate of preterm birth at 8.4 percent, with rates increasing steadily through theseasons and peaking in spring at 9.2 percent.Lisa Bodnar and Hyagriv Simhan observed the spike when examining data fromabout 85,000 deliveries at Magee-Women’s Hospital of UPMC. Bodnar is a PhD assistantprofessor of epidemiology, of psychiatry, and of obstetrics, gynecology, and reproductivesciences. Simhan is an MD assistant professor of obstetrics, gynecology, andreproductive sciences.The researchers say that the reasons for the spring spike are unknown but couldbe attributed to factors such as environmental allergens, dietary changes, and viralinfections. Couples needn’t shy away from trying to conceive children in the spring,say Bodnar and Simhan. They see their study as a guidepost for future research intothe roots of preterm birth, one of the most commoncomplications of pregnancy. —Joe MikschFOOTNOTEStephen Esper (MD ’07) recently strutted aboutin a bathing suit and Godzilla mask, then stompedon a sand castle. Esper was named winner of thisyear’s inaugural Mr. Pitt Med pageant, a benefit for theKenyan Pediatric HIV Project. The student’s angry lizardact (part of the swimsuit competition)—along with hisfiddle performance and Chewbacca impression—netted him the title.PANCREATIC CANCER’SGENETIC HELPERThe University of Pittsburgh’s David Whitcomb and a team of researchers aredigging down to the root causes of pancreatic cancer, an aggressive and migratorykiller. The group recently discovered a gene, palladin, linked to increasedsusceptibility for the form of the cancer that runs in families.And by studying the genetic makeup of one family especially vulnerable topancreatic cancer, Whitcomb has pinned down where the palladin mutation islocated: chromosome 4q32-34.Palladin is responsible for maintaining cell shape and function, saysWhitcomb, an MD/PhD professor of medicine, of cell biology and physiology,and of human genetics. When palladin malfunctions, pancreatic cells morph.They behave like amoebas, as Whitcomb puts it, crawling away and allowingthe cancer to spread rapidly.These findings will help scientists develop a test to identify people likely todevelop pancreatic cancer. Earlier detection will allow for earlier intervention inthe form of laparoscopic surgery and other therapies. —JMSUMMER 2007 3

A&QArt for Doctor’s SakeObserving the way a patient sits, talks, or stares is an important skill for a doctor. So how do youteach medical students to read other people? Maybe study a discipline whose practitioners lookat people all day long.That’s exactly what Dean Arthur S. Levine (above) wants Pitt med students to do. He’s thedriving force behind a collaboration between the School of Medicine and The Carnegie Museums ofPittsburgh’s art programs, including its Museum of Art, where Marilyn Russell (shown left) serves ascurator of education, and The Andy Warhol Museum, where Jessica Gogan (shown right) is assistantdirector for education and interpretation. Students will study Carnegie collections to learn how artistssee their subjects. It’s an idea that has caught on at a few other medical schools as well.On what doctors need to know that artists can teach themLevine: When we see how a portrait artist visualizes another human being, we have a great dealto learn about diagnostic acuity. If I look at the portrait of King George by Velázquez or a portraitof the Madonna by Picasso, we begin to think about what the artist was seeing in that person, andwhat that person was feeling and thinking and perhaps articulating in ways that have commonground with how a patient and a physician interact.How looking at art improves one’s ability to practice medicineRussell: I think they’re natural partners. Developing an interpretation of a work of art orfinding personal meaning in it demands careful looking at exactly what the artist has provided.Viewers must consider not only the subject matter depicted, but even more importantly, subtleelements such as quality of brushstroke in a painting, body language and facial expression infigurative works, and the relationship and placement of objects within a composition. The contextin which one experiences a work of art as well as prior knowledge can also affect what one takesaway from the process of looking. It’s easy to see how these would be important factors in themedical profession.A question for usLevine: Has a particular painting or artist caused you to view patients differently?—Interview by Reid R. FrazierCAMI MESANext GenerationJustin Baca can be found ensconced in chemistryprofessor Sanford Asher’s lab, where he has beentasked with making his colleagues cry.Baca, a University of Pittsburgh MD/PhD student,isn’t cruel; he just needs the tears to help developa glucose sensor that could be placed inside a contactlens to monitor blood sugar in diabetic patients.When glucose levels rise, the crystalline structure ofnanoparticles suspended in a gel swells, causing thegel to change color. If you were to see a small bluepanel in your lens, then, Baca says, it might be time forinsulin. Baca, Asher, and others recently published onthe topic in the Journal of the American Society for MassSpectrometry.Baca finished his second year of medical school in2003 and plans to have his MD degree in the bag in2009. In the interim, he’s been working on a Pitt PhDin chemistry. He has his eye on a career in emergencymedicine.Pitt geriatric psychiatry fellow Alexandre Dombrovskistudies late-life depression, and his early work is makinga mark. He recently won the American Associationfor Geriatric Psychiatry’s Member-in-Training ResearchAward for a paper studying the efficacy of drugs andpsychotherapy in elderly people who suffer fromdepression.The study, to be published in the Journal of theAmerican Geriatrics Society, found that depressedpatients taking the antidepressant drug paroxetinereported better long-term social and emotional role functioningthan those on placebo. The work was funded bythe National Institute of Mental Health and the John A.Hartford Foundation.Giorgio Raimondi won The Transplantation Society’sresearch training fellowship—one of four research fellowshipsparceled out by the society in 2006. The PhDis a research associate in Professor Angus Thompson’slab at the Thomas E. Starzl Transplantation Institute.Working with mouse models, Raimondi tries to inducetolerance by isolating T-cells, treating them in vitro sothat they recognize a transplanted organ as “self,” andreintroducing them into the mice.“This area has been pretty hot for the past fiveyears,” Raimondi said. “I really want to help create arobust state of tolerance, an acceptance of the organ”that would reduce or eliminate the need for immunosuppressivedrugs. —JM4 PITTMED

Sweets and StressA few years ago, the University of Pittsburgh’s JanetAmico noticed how women she saw as patients wereresponding to stress and anxiety. She’d sometimes hearthem talking about grabbing sweets or carbs to alleviatestress. Men, however, never seemed to talk about that.Since then, Amico, an MD professor of medicine andof pharmaceutical sciences, and Regis Vollmer, a PhDprofessor of pharmaceutical sciences, have shown thatoxytocin, a hormone associated with maternal bonding aswell as dampening the blow of stress and anxiety, couldhave a role in keeping us from grabbing another slice ofpie. The researchers monitored the feeding behaviors ofa colony of normal mice and another of genetically engineeredmice without the hormone. When the researchersaugmented the animals’ water with sugar, the oxytocindeficientmice went on a binge, consuming four to fivetimes as much water as they normally would. They alsooverdid it with carbohydrate-enriched water.Amico and colleagues have also identified moreanxiety and greater stress responses in female, butnot male, oxytocin-deficient mice versus normal mice.She has broadened her studies to explore whether theenhanced consumption of sugar and carbohydrate solutionsand greater responses to stress and anxiety aresomehow related.“It’s still early to speculate,” says Amico, about thehormone’s role in humans, but the research suggests thatsome people’s inability to say no to dessert could stemfrom an oxytocin problem. —Erica LloydCATHERINE LAZUREIS RICKETS ON ITS WAY BACK?PHOTO RESEARCHERS, INC.Our modern indoor lifestyles couldbe contributing to a reemergenceof rickets.Rickets is usually associatedwith developing countries. InNorth America, first with theaid of cod liver oil supplements,then ultraviolet lampsand vitamin D–enriched milk,the bone-softening diseasefound in children was all buteradicated by the 1930s.Kumaravel Rajakumar,assistant professor of pediatricsat Pitt, has foundevidence that leads him tobelieve it might be on the risehere again. Half of the AfricanAmerican Pittsburgh-areachildren he studied (a sampleof 42 between the ages of 6and 10) were vitamin D deficient. If years go by without children gettingenough of the vitamin, they can develop rickets.“Rickets is back in North America in waves,” Rajakumar says,even in sunny regions. Though rickets is not a disease physicians arerequired to report to health authorities, small studies like his ownhave brought Rajakumar to this conclusion.“People with darker skin are more susceptible, needing up to sixtimes the amount of sunlight required to generate an adequate supplyof vitamin D in a light-skinned person. People in general aren’t gettingenough sunlight, mothers are depleted of vitamin D [through breastfeeding],and children don’t get enough of it in breast milk and developrickets,” says Rajakumar.Children and breast-feeding mothers should get more sunlight andconsume more vitamin D–rich foods like fortified milk and other dairyproducts, he says. Vitamin D deficiency can also make one more susceptibleto prostate cancer, multiple sclerosis, breast cancer, and diabetes.Rajakumar received National Institutes of Health funding to monitorvitamin D levels in light- and dark-skinned children. —JMSUMMER 2007 5

EARLY SIGNSAs Robert Rogers sat on hisporch preparing to give a classon saline lung flushing, his 11-year-old son approached himand asked:“What are you doing?”“Preparing a lecture on lungwashing,” Rogers said.The boy disappeared; ahalf-hour later, he handed hisdad a drawing.“My Dad The Lungwhasher”(sic) was the firsteditorial cartoon by Robert“Rob” Rogers, on staff at thePittsburgh Post-Gazette since1993; his work is now syndicatednationwide.When Rob Rogers startedhis professional cartooningcareer in 1984 at the PittsburghPress, his family often servedas muse and model. In themeantime, his father, a Pittprofessor of medicine since theearly ’80s, founded the department’sPulmonary, Allergy,and Critical Care Division, aswell as the clinical pulmonaryphysiology lab at UPMCPresbyterian. Artistry runs inthe family: The elder Rogerspaints. —Meghan HolohanCOURTESY ROB ROGERSAppointmentsThomas Gleason, an expert in aortic surgery, has joined Pitt. The cardiacsurgeon’s proficiency runs the gamut from the mending of aortic aneurysmsto the repair of aortic and mitral valves.Gleason, an MD, comes to Pitt from Northwestern University’sFeinberg School of Medicine in Chicago. Here, he has become thedirector of the Center for Thoracic Aortic Disease at the UPMCHeart, Lung, and Esophageal Surgery Institute. He serves as associateprofessor of cardiac surgery in the School of Medicine.In addition to assuming his surgical responsibilities, GleasonGleason will oversee clinical and translational research aimed at treatingthose with thoracic, aortic, and valve-related diseases.In many cases, asthma is a nuisance, making people reliant oninhalers or oral medication so that they can breathe freely. Inother instances, asthma can be debilitating. New Pitt med recruitSally Wenzel focuses on the latter cases.WenzelFormerly a professor of medicine at the National Jewish Medicaland Research Center at the University of Colorado Health SciencesCenter in Denver, the MD plans to continue to develop treatments forsevere asthma at Pitt. Here, she’ll hold the positions of professor of medicinein the Pulmonary, Allergy, and Critical Care Division and director ofits Asthma, Allergy, and Airway Research Center. Wenzel explores geneticfactors contributing to severe asthma. She also hopes to further delineatethe physiological differences that separate severe asthmatics from thosewith mild and moderate cases.While at the Cleveland Clinic, obstetrician Stephen Emery wasamong the first to perform a procedure that used a needle andballoon catheter to penetrate a mother’s uterus and restoreblood flow in a fetal heart. Left untreated, the defect preventsEmeryorgan growth and can necessitate a heart transplant. Since coming toPitt, Emery has taught the technique to physicians here and says theyare ready to perform it in Pittsburgh.Emery joins the Pitt faculty after serving as cofounder and codirectorof the Fetal Care Center at the Cleveland Clinic and assistant professor atthe Cleveland Clinic Lerner College of Medicine of Case Western ReserveUniversity.At Pitt, Emery serves as assistant professor of obstetrics, gynecology,and reproductive sciences. He is pulling together a multidisciplinary teamof surgeons, radiologists, and other specialists to join Magee-WomensHospital of UPMC’s Center for Fetal Medicine, which he leads. He plans todevelop a comprehensive program for fetal intervention. —JM6 PITTMED

CLOSERCLOSERPRE PITT MEDAlexis Chidi doesn’t know if shewants to get her MD immediatelyor after earning a master’s degreein public health. She’s captivatedby basic neuroscience, yeteconomics, French, and politicalscience intrigue her as well.As a University of Pittsburghrising junior, the Rancho PalosVerdes, Calif., native has sometime to make her decision. Chidiknows that if she finishes herundergrad years with a 3.7 GPA orhigher and participates in appropriatemedicine-related extracurricularactivites, she’s guaranteedadmission to the School of Medicine.The “freshman guarantees”program attracts top high schoolersto Pitt by promising them aplace in the University’s graduateand professional schools. Theprogram accepts about five premedstudents a year.Chidi has a relaxed mannerwhich belies her drive. Afterher freshman year at Pitt—shematriculated at 16—Chidi did asummer undergrad research fellowshipat the California Instituteof Technology, during which shestudied language generation asit relates to defects of the corpuscallosum, the structure that connectsthe brain’s hemispheres.She developed and led theproject and, as she says jokingly,“Got a team of grad students topush around.”This summer, she may investigatestem cell research througha National Science Foundationprogram. Or, maybe, land a publichealth internship in GovernorArnold Schwarzenegger’s office.Perhaps she’ll work on a servicelearningproject in Tanzania. Orshe might just take some morecourses in organic chemistry.Chidi says she’ll figure it allout between classes, sorority soccerteam games, and her dutiesrelated to serving in the studentgovernment, as vice presidentof her sorority, and on the PittProgram Council.—Joe Miksch—Photo by Derek WahilaSUMMER MONTH 2007 2005 75

INVESTIGATIONSExplorations and revelations taking place in the medical schoolAfter trauma, the body generates afrenzy of cells that produce the enzymearginase, which shuts down the immuneresponse. Oddly, these cells (shown witharrows) come from our immune system.The same thing seems to happen in certaincancers. Juan Ochoa believes understandingthis mechanism will lead tolife-saving diets for trauma patients andperhaps new cancer treatments.FEEDING TIMEA DIET THAT MAY HELP TRAUMAAND CANCER PATIENTSBY ERICA LLOYD8 PITTMED

COURTESY J. OCHOAJuan Ochoa started his doctoringcareer as a general practitioner with abent toward preventative medicine inthe 1980s. That was in the 8,000-foot-high mountain town of Santa Barbara,Colombia, a few hours’ drive from Medellín,where he’d spent his formative years. He evenhad a weekend radio show, “The Doctor atYour Home.” But Ochoa was fresh out ofmedical school, a bit naive, he says, and lesseffective than he expected to be. He wouldencourage women to breast-feed, for example,not realizing that practice was stigmatized inthe rural area. Even the doctor on the radiowasn’t going to change people’s minds.“I went there naively thinking I was goingto be a missionary. And I left thinking, ‘This isfar more complex than I ever thought.’”Ochoa decided to specialize. Today, as atrauma surgeon and basic scientist, he is still acreature of prevention.The questions the University of Pittsburghprofessor of surgery and critical care medicinepursues now to save and improve lives are notso much about how to get people to changetheir behaviors, but how to convincecells to do so.Since he first came to Pitt forclinical and research training in 1991,Ochoa has wondered: What do you feed traumapatients? Especially those who can’t feedthemselves? Many surgeons wait a few daysafter surgery, until the bowels are functioningagain, before feeding. Ochoa believed thatthe right diet, given earlier, would strengthenpatients, helping them survive and stave offinfection.Studies have since suggested Ochoa wasright. But feeding trauma patients is not asimple matter of inserting a tube and turningon a few monitors. The science behind nutritionafter trauma is at least as complex as thesocial taboos of Santa Barbara. Our bodiesare sometimes better able to cope with a littlestarvation than force-feeding, notes Ochoa.Trauma patients, in particular, are highly susceptibleto infection. More than 50 percentwith severe injuries are likely to end up withinfections. And feeding someone the wrongformula can actually make it more likely thepatient ends up on the unfortunate end ofthose statistics.“For some reason, the injury process createsa state of immune suppression,” Ochoa says.Many surgeons began using what’s called an“immune-enhancing” diet for surgical patientsdeveloped several years ago. That was on theheels of medical science’s realization that nitricoxide, the toxic gas your car coughs out ofits exhaust pipe, is also manufactured by ourbodies as part of the immune response. Thediet includes, among other things, the aminoacid arginine, a precursor to nitric oxide.Ochoa believes the diet is probably appropriatefor trauma patients and has tested safefor most other surgical patients. But surgeonsaren’t in agreement about that. There’s noprotocol in the United States—use of the dietdiffers from doctor to doctor and case to case.(The European society concerned with nutritionamong surgical patients recommendsusing such diets before elective surgery.)Now Ochoa believes that doctors are onthe cusp of understanding how an argininediet works and why it may be helpful for somepatients and not others. His family ties havehelped him make sense of the science.His brother, Augusto Ochoa, is interimdirector of Louisiana State University’s StanleyS. Scott Cancer Center. When Augusto Ochoawas a researcher at the National CancerInstitute in the ’90s, he began to answer aquestion that perplexed many cancer researchers:Why don’t our immune systems put up abetter fight against cancer cells?“For many years,” Juan Ochoa explains,“doctors have been trying to boost the immunesystem to make it reject the tumor. But in agood number of patients, those lymphocytesthat have been recruited to get rid of thetumor just don’t seem to work.”In the early ’90s, cancer researchers, notablyAugusto Ochoa, recognized that a peptidecalled the “zeta chain” was missing in lymphocytes(specifically T cells) of cancer patients.“People didn’t know why it was lost, butthey knew it was important,” says Juan Ochoa.T cells play a vital role in defending cells fromviruses, foreign tissue, and other unwelcomeguests.Years later, in 2001, the Ochoa brothersbegan publishing reports showing that argininewas essential to maintaining the zetachain. Around the same time, a Japanesescientist showed that trauma patients weremissing the zeta chain.What do you feed trauma patients who can’t feed themselves?Juan Ochoa had learned from his owninvestigations that arginase, an enzyme thatmetabolizes arginine, is present at elevatedlevels in the tissue of trauma patients. Patientswith more arginase don’t do well. If they survive,they are sicker and stay in the hospitallonger. The high levels of arginase somehowinhibit the ability of the injured body to keepthe needed arginine in store.The Ochoa brothers began exploringwhether the immune system is dampenedthe same way in cancer patients. They foundthat arginase is elevated in the tissue of cancerpatients, much like it is in trauma patients.The brothers also learned what arginase wasup to: At the heart of the immune response, itrobs the arginine necessary to build the zetachain. That leaves the T cell unable to proliferateto help fight off intruders and leaves thepatient unprotected.Augusto Ochoa and collaborators havesince injected arginine into the tumor of amouse. That therapy stopped the tumor fromgrowing further.Juan Ochoa believes that immune-enhancingdiets work similarly: A high concentrationof arginine restores the zeta chain, allowing theT cell to do its job to fight off infection.“It’s not proven. But we’re closing the loopon that,” he says.He’s anxious to start refining a diet forprecommercial testing in trauma patients.(Arginine, for example, doesn’t taste great andcan have adverse effects. Juan Ochoa is lookingtoward substituting it with citrulline, amore palatable amino acid found abundantlyin watermelon. Citrulline works the same wayand seems to be safer.) “Now that we knowthe mechanism, we can make better diets,”he says.He’s optimistic about the possibilities: “Soif we could block the [process that cuts out thezeta chain], we could potentially have a treatmentfor cancer. We could also have a potentialtreatment for infection in trauma.”He suspects that the immune system isdampened the same way in leprosy and tuberculosisand wonders whether those diseasescould be managed through diet as well. ■Jessica Mesman contributed to this article.SUMMER 2007 9

Birds have it. Beeshave it. Even yeast haveubiquitin (shown here).In humans, it helps uskeep going by taggingdefective proteins forthe proteosome, whichchews them up into theirconstituent amino acids.COURTESY CORNILESCU G, MARQUARDT JL, OTTIGER M, BAX A,JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, V120, 6836-6837, © 1998.HEAVILYENGAGEDA FORMERLY HIDDEN PROTEINSHOWS UP IN JUST ABOUTEVERY LIFE-FORM AND TONSOF IMPORTANT PROCESSESBY JAMES SWYERSIn the 1970s, American researchers were looking for clues tothe cause of the human autoimmune disease myasthenia gravis.They found a protein that appeared to have some of the propertiesthat could make it a potential cause of MG. When researchersadded the protein to certain types of human immune cells, those cellsbecame more specialized. Investigators also were intrigued by the factthe protein was very good at attaching itself to other proteins, suggestingit had some immune properties.Unfortunately, their candidate protein flunked the final, and mostcrucial, test. Researchers believed that for the protein to be involvedin MG, it needed to be unique to the thymus gland, which is whereimmune cells get their marching orders. But when they looked forthe protein in other kinds of cow tissue, the medium of their first10 PITTMED

experiments, it was in every one. Then theyfound it in every type of tissue they lookedat. The stuff was in pigs, guinea pigs, mice,plants, insects, people, even yeast. The onlyplace it didn’t show up was in a few primitivemicroorganisms.In 1974, the scientists introduced their newprotein—aptly named “ubiquitous immunopoieticpolypeptide” (later shorthanded to“ubiquitin”)—in a paper in the Proceedings ofthe National Academy of Sciences. Then theypromptly abandoned it because it wasn’t thethymic hormone they sought. An aside at theend of the PNAS paper noted that the proteinoccurs so universally it must be an “integralfeature” of nearly all living things.Ubiquitin would not resurface as a researchtopic until five years later when two Israeli scientists,collaborating with an investigator atthe University of California, Irvine, set out tofind the explanation for a recently discoveredphenomenon known as “energy dependentprotein degradation.”Researchers in the 1970s had noted thatwhenever there was a burst of amino acidsreleased inside cells, there was a correspondingconsumption of energy. Looking for whatwas using the energy—figuring it was chewingup proteins and releasing amino acids inthe process—the investigators turned up whatthey thought was a newly discovered protein.It seemed to be able to degrade other proteinsunder certain conditions. Upon talkingto their colleagues and searching the scientificliterature, they realized what they’d comeupon was ubiquitin.In a flurry of studies in the early 1980s,researchers showed that ubiquitin does notdegrade proteins directly but rather flagsthem for demolition by a long, hollow moleculecalled a proteosome. It takes at least fourubiquitin tags for a protein to be targetedfor destruction. As the protein is degradedby the proteosome, the ubiquitin moleculesare liberated, free to search out potential newtarget proteins for disposal.And scientists made another importantdiscovery: Ubiquitin mostly tags abnormalproteins for destruction. Unfortunately, ittook a few decades before the full implicationof this latter finding was appreciated. As oneretelling of those events recently noted, ubiquitinresearch “was little more than a backwaterof biochemistry studied by a handful oflaboratories” for many years to come.Ubiquitin’s status as a topic of researchinterest did not change dramatically until2003, when the Israelis and one of theirAmerican collaborators were given the LaskerAward for their work on the ubiquitinproteosomepathway. A year later, the twoIsraelis and another American colleague wereawarded the Nobel Prize for Chemistry.Scientists now recognize ubiquitin as amaster regulator of a broad host of cellularprocesses. They suspect that alterations in theubiquitin-proteosome protein-disposal systemfactor into a number of diseases, includingneurological conditions, liver diseases, eyediseases, and a variety of cancers.Just as the greater scientific communitywas beginning to recognize the importanceof the ubiquitin-proteosome pathway, YongWan, now a PhD assistant professor of cellbiology and physiology at the University ofPittsburgh School of Medicine, was arrivingat Pitt after completing his postdoctoral trainingat Harvard University.At Harvard, Wan had worked for cellbiologist Marc Kirschner. One of the first tounderstand the importance of the pathwayfor normal cell functions in the mid-1990s,Kirschner and his lab had discovered a ubiquitinligase known as anaphase-promoting complex(APC), which is involved in making surethat cells divide properly. Kirschner assignedWan to work on APC, and Wan broughtthat project with him to Pitt in 2003, wherehe was one of just a handful of investigators(including the medical school’s dean, ArthurS. Levine) interested in this relatively new areaof inquiry.Today, Wan’s lab is one of several dozenat Pitt delving into some aspect of this multifacetedenzyme. Others are investigatingubiquitin’s role in neurological conditions,including Alzheimer’s, as well as xerodermapigmentosa, an inherited disease that makespeople extremely sensitive to natural sunlightwhile putting them at high risk for skincancer. The disease can inhibit the effectsof radiation therapy and chemotherapy ontumors, promote the growth and proliferationof cancers, and influence circadian rhythms.Wan has several large grants from theNational Cancer Institute and the AmericanCancer Society to not only investigate APC’srole in normal cell division but also to look atwhether environmental factors, such as chemicalsor radiation, might damage APC or causeother alterations in its activity.“The major role of APC is to control theseparation of chromosomes during cell divisionby ungluing the chromosome strands.Deregulation of this separation process usuallyresults in catastrophic alterations in the shapeand number of chromosomes in a cell, whichis a hallmark for many types of tumor cells,”Wan explains.His laboratory, based at the University ofPittsburgh Cancer Institute, also looks intoubiquitin’s role in stem cell maturation. Wanbelieves the ubiquitin-proteosome system actslike a licensing agency, allowing stem cells tobecome specific types of cells, such as muscleor liver cells, by orchestrating the degradationof all but one type of signal.Others at Pitt have suggested that ubiquitininfluences how we perceive the world.The laboratory of Yong Tae Kwon, aPhD assistant professor in the Center forPharmacogenetics in the School of Pharmacy,explores a pathway in the ubiquitin-proteosomesystem called the N-end rule pathway.Wan believes the system acts like a licensing agency,allowing stem cells to become specific types of cells.Takafumi Tasaki, a PhD and a memberof the Kwon lab, has uncovered indicationsthat the pathway is involved in regulatingsensations in mice. “It is only a hypothesisright now, but we think it may be importantin regulating synaptic transmission in sensorysystems, including smell, taste, vision, andhearing,” he says.Others in the Kwon lab have shown thatthe enzymes in the N-end rule pathway playessential roles in heart formation, blood vesseldifferentiation, male reproduction, chromosomestability, neural tube development,muscle protein degradation, fat metabolism,and blood development.Although it is hard to predict where all ofthis research will lead and when it will turninto treatments for major diseases, it is safe tosay that ubiquitin research is likely to becomemuch more, well, ubiquitous in the comingyears at Pitt.“When I arrived here a little more thanfour years ago, there was not a lot of researchin ubiquitin going on,” recalls Wan. “But now,research in this area is booming.” ■SUMMER 2007 11

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COVER STORYA BETTER LIFE FOR THEIR CHILDRENSOMETIMES MEANS TRANSPLANTSPHOTOGRAPHY | CAMI MESATEXT | JOE MIKSCH“PLAIN PEOPLE,”COMPLEX CURESIn a parking lot populated by a dozen or so hundreds-of-horsepower cars and SUVs also sit acouple of one-horsepower conveyances: Amish buggies. This is the Clinic for Special Childrenin Strasburg, Pa. Amish and Mennonite men constructed the clinic here in 1991 and expandedit in 2001.On the front porch, a docile black dog named Bowie greets patients and visitors. Inside are womenwearing unadorned clothes and bonnets. (The Amish, Mennonites, and others who settled the area in the1700s in search of a humble life and religious freedom often call themselves “the Plain People.”) Childrenplay in the waiting room. One child roots through a toy chest full of Beanie Babies. Sunlight streams intothe building from 78 windows. Down a hallway where skylights brighten the oak floor and fir beams (heldtogether with wooden pegs rather than nails, the custom for Amish and Mennonite construction), and pasta genetics lab, a family sits in an alcove in close conversation with physician Kevin Strauss.The family is Mennonite. They are from southern Alabama, not far from the Florida panhandle.Their baby daughter is squirming on her thin father’s lap. The girl has a rare genetic condition calledmaple syrup urine disease (MSUD). It is more common by orders of magnitude among Amish andMennonites—the ratio is one in three-hundred for them and perhaps as high as one in a million forthe population at large, says Strauss. MSUD, which gets its name from the sweet smell of the afflictedchild’s urine, is a metabolic disease that causes amino acids to accumulate in the body. It can lead tobrain swelling, neurological damage, and death. The only cure is liver transplantation. Although MSUDis not a liver problem per se, a new liver compensates for the lack of critical enzymes normally foundthroughout the body. Almost immediately after transplantation, an MSUD patient’s metabolic healthreverts to normal.The Clinic for Special Children, cofounded by West Virginia native and Harvard-trained physicianHolmes Morton and his wife, Caroline Morton, is one of the best places to get diagnosis and treatmentfor genetic disorders particular to the Amish and Mennonites, including MSUD. Children’s Hospital ofPittsburgh of UPMC has become the clinic’s go-to hospital for the curative transplant.Holmes Morton, who cofounded the Clinicfor Special Children (shown left and right)near Lancaster, Pa., now refers all of histransplant patients to Children’s Hospitalof Pittsburgh. In the past three years, Pittsurgeons have performed 38 life-enhancingliver transplants on clinic children.SUMMER 2007 13

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OPPOSITE PAGE AND BELOW: PediatricianKevin Strauss consults with a familyfrom Alabama about the viabilityof a liver transplant to treat theirinfant daughter with MSUD.FAR LEFT: Laboratory director ErikPuffenberger heads the clinic’sgenetics lab. NEAR LEFT: Morton tendsto paperwork.Of course, transplantation has its risks. In addition to challenges presented by the surgery itself, patientsmust perpetually take immunosuppressants. Yet Pittsburgh boasts an overall survival rate among pediatricpatients of 83 percent 10 years after a liver transplant. And all 38 of the Clinic for Special Children’spatients transplanted at Children’s—28 because of MSUD—are thriving.The Alabama family has come to the clinic to find out for themselves about the benefits and pitfalls of transplantation.The young father (the family asked that their names not be used), dressed in black trousers and a whitebutton-down shirt with a cell phone hanging from his belt, says to Strauss, “My opinion was [the Mennonite community]doesn’t do transplants.” That was, he adds, until a member of a Mennonite family close to his did.The father came prepared with a list of questions regarding mortality on the operating table, immunosuppression,rejection, maintenance of MSUD through diet, and cost. (Mennonites and the Amish typically do not carry healthinsurance. It’s a pay-as-you-go process for them, with material help given by friends, family, and other members ofthe community. The cost of a liver transplant, Strauss says, is equivalent to about a decade of typical treatment, andtreatment can go on for 30 or 40 years or longer.)As the father talks, a toy placed next to the band of preschoolers sitting on the floor erupts into a rousing renditionof “London Bridge.” Amid the commotion, Strauss does his best to allay the man’s fears.“One thing we can tell you—one thing we are obligated to tell you—is that [transplantation]cures MSUD in every case and cures it 100 percent,” Strauss says. “There’s no longer aneed for a special diet, there’s no need for blood testing. That’s it.”What that means, Strauss tells the father, is normalcy. There will be no metabolic crisis, nodietary restrictions (MSUD patients have to carry a special dietary protein powder with themat all times), and no risk of MSUD-related brain damage or death. There can and likely will bemedical problems related to the transplant, he says, but “it’s a good trade-off.” To reap these benefits,Strauss continues, leaning forward, “You have to go where they know what they’re doing.That’s Pittsburgh. You have to go to Pittsburgh. We’re partners. They can manage any crisis.”The clinic’s relationship with Pitt has taken root throughout the past three years under thedirection of George Mazariegos (Fel ’93), an MD associate professor of surgery at Pitt and directorof Pediatric Transplantation at Children’s. Morton and Strauss worked with him—alongwith colleagues such as Jerry Vockley, MD/PhD chief of the Division of Medical Genetics atChildren’s and professor of pediatrics and human genetics at Pitt, and David Finegold, an MDprofessor of pediatrics, medicine, and human genetics at Pitt—to develop transplant protocolsto deal with and stave off the metabolic crises potentially faced by MSUD sufferers.Strauss acknowledges there is resistance to transplantation in certain segments of theMennonite and Amish communities, particularly those near the clinic.“From the beginning, there’s been opposition. People have felt that Dr. Morton and theclinic are right here and can manage MSUD. But Dr. Morton and I both know we can’t fullyprotect anyone from the risks of MSUD,” Strauss tells the family.The father turns to his wife, then looks back to Strauss and says, “We’re going to go homeand think.”SUMMER 2007 15

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OPPOSITE PAGE: Dustin Hahn, who has MSUD,awaits a transplantable liver. NEAR LEFT:Morton and his wife, Caroline Morton, theclinic’s executive director, relax after a dayof seeing patients.EDITOR’S NOTE: Readers may be aware thatmembers of certain Amish and Mennonitesects prefer not to be photographed, a practicePitt Med magazine respects. All patientfamilies pictured here agreed to be part ofthis photo-essay.Dustin Hahn and his parents, Dawn and Kevin Hahn, have already made their decision. Dustin will have histransplant. A cheery homeschooled seventh-grader from Lititz, Pa., who’s quite comfortable in the presenceof adults (perhaps from a lifetime of dealing with doctors), Dustin came to the conclusion he was ready asthe 2006 –2007 ice hockey season approached.“He asked Dr. Strauss if he could play on a hockey team,” Dawn Hahn says. She reports that Strauss said Dustincould, but it would mean a lot more work to keep him healthy, because soft bones are a consequence of MSUD.As the Hahns discuss Dustin’s potential hockey career (he’s a Philadelphia Flyers fan), Strauss joins them in thewaiting room. Picking up on the conversation, Strauss says, “Hockey for [Dustin] is just the tip of the iceberg. Thereare benefits in terms of attention and education and employment. Adults with MSUD don’t take as good care ofthemselves as their parents did when they were children. Thereare mood disorders to consider. About 30 percent of adultswith MSUD are on antidepressants—that’s three or four timeshigher than the general population.”Dustin has been on the liver transplant waiting list sinceJanuary. Since then, Children’s has called twice telling theHahns a liver was available, but both times they got a follow-upcall before they could make the four-hour drive to Pittsburgh.The organs were not suitable for transplant, they were told.“I was excited,” Dustin says, “and a little scared. My heartwent down when we found out it wasn’t going to work, but Igot over it. It’s practice.”“We don’t want a lot more practice,” his mother chimes in.So Dustin waits for his opportunity to eat “regular” food(he wants a bacon cheeseburger and a Frosty from Wendy’s),play sports, and be able to concentrate better in school. Heis hopeful, and, in fact, his greatest fear seems to be that thedoctors and nurses at Children’s will try to turn him into aPittsburgh Penguins fan. “Flyers all the way,” he says. ■Dustin Hahn received his transplant shortly before Pitt Medwent to press.SUMMER 2007 17

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FEATUREWHOSE LAST WISHES DO WE HONOR?BY ELAINE VITONETHE MODERNDEATHBEDStatistically speaking, most of us will die like Gene Smith isnow—lying in a hospital bed amid the rhythmic chirping ofmachines. He has a life-limiting, chronic illness—one of theusual suspects that kill Americans—and has been seeing a specialistfor some time. At his last appointment, he got the news: Treatmentisn’t helping anymore.Smith’s nursing home transferred him here last night when he beganhaving trouble breathing, which the hospital staff says may or may notbe due to his chronic illness. Now his blood pressure is dangerouslylow. He gasps inside his facemask, though it’s putting concentratedoxygen in his lungs. His wife, Nancy Smith, holds his hand.Hospitalist Jane Miller walks in and introduces herself. “I’m sorry tobe meeting you under these circumstances,” she says, standing besidethe bed. “So, what’s been going on?” Her eyes bow with concern. Fromreading his chart earlier, she knows—as the Smiths do—that Smithhas only a few months, at best. At worst, he will die much earlier—certainly within 24 hours if he isn’t put on a respirator soon.Where do we fall shortof providing “the gooddeath,” and what canwe do to improve? ILLUSTRATIONS | CATHERINE LAZURESUMMER 2007 19

Dr. Jones. You don’t know me and have noreason to trust me, but we have to makesome life-and-death decisions for your husband,and fast.’”The doctors’ difficulty with this simulationspeaks to a larger issue. Althoughsome medical schools now offer basic communicationcourses, training specific to thedeathbed is hit-or-miss. A 1991 study foundthat some schools offered no training in endof-lifesituations at all. New doctors might be alittle better prepared. In 2003, a study reportedthat 60 percent of fourth-year students surveyedhad been trained to discuss treatmentwithdrawal with patients or their families.Yet 82 percent of students and residents saidthey’d taken no courses in end-of-life care. Arecent survey found only about 5 percent ofpracticing oncologists have had anyform of communication training. Alltoo often, doctors are ill prepared forthe needs of dying patients and theirfamilies.Though the details vary, researchshows that dying patients consistentlydescribe the same desires: Theywant to manage their pain and symptoms,feel a sense of preparednessand completion, be valued as a wholeperson, and remain clearheaded andable to make decisions for themselves.Without clear communicationbetween doctor and patient, all of theabove can be difficult.Although Barnato empathizes withher study’s participants, it worries herthat their decisions regarding Smith’streatment have been “all over themap,” from intubation in the ICU allthe way over to what Smith actuallywants: palliative care, a subspecialtyfocused on providing comfort, dignity,and control to patients with lifelimitingillnesses. However, the actorsare trained not to ask for it. “Even in asimplified case in which the simulatedpatient has underlying goals and preferencesthat are scripted and waitingto be unearthed,” says Barnato, “thepatient’s treatment plan is at the whimof the physician.”Barnato says that for the doctorsparticipating in the study, it’s all amatter of perspective. Do they seethe big picture or the immediateproblem—the forest or the trees? Ifthey are focused on the trees, they’relooking at the numbers, adjustingSmith’s oxygen, concentrating ongetting him through the next 24hours. If they see the forest, theyrecognize that there is much more atstake, and now is the time to addresshis wishes directly. The longer thisdiscussion is put off, skirted, orderailed by talk of vitals and treatmentoptions, the less likely it is that Smithwill die the way he wants to.Palliative care began in the United Statesin 1974, when the country’s first hospicewas founded (the Connecticut Hospice).However, it only became formally recognizedas a subspecialty in October 2006. In 2005,the American Heart Association includedpalliative care recommendations in its guide-SUMMER 2007 21

lines for the first time in the organization’shistory.At the state level, a new Pennsylvanialaw covering decision-making proceduresfor terminally ill patients took effect thisFebruary. Incidentally, that was just daysbefore Governor Ed Rendell’s administrationreleased a 40-page report of recommendationsfor improving end-of-life care. The document’s160 recommendations aim to improveresearch, outreach, advance-directives policy,healthcare-fi nance structures, professionaleducation, sensitivity to the needs of specialpopulations, and palliative care standards—especially in acute-care hospitals, where mostPennsylvanians die.On February 9, scholars from around theworld gathered on Pitt’s campus for a seminaron end-of-life issues, hosted by Pitt’s CulturalStudies Program and School of Medicine.The springboard for the discussion was TheContemporary Deathbed, a book by emergency-medicinespecialist and cultural historianJohn Tercier of the University of California,San Francisco. The bookfocused on the iconicimage of death in themedia—the heroic CPRattempt that often takesplace after a patient’s lastbreath. Tercier questionswhy CPR has been so central to resuscitativeprocedures across a gamut of cases, eventhough it has been proven effective onlywhen administered immediately after certaintypes of cardiac arrest. “For a number of yearsnow,” he writes, “medical personnel, whilepumping on the chests of the dying, havebeen asking themselves, ‘Why are we beatinga dead horse?’”Perhaps the question now is: How do westop?It’s not news that few Americans want toend their time on earth in a hospital, withintensive—not to mention expensive—lifesustainingtreatment. Yet that’s exactly whatmost get. In the last three decades, 27 percentof the total Medicare budget has been spenton treatment during Americans’ last year oflife and, of that, about 40 percent in the lastmonth.Given that so many doctors are uncomfortableeven asking patients about theirwishes, it’s not surprising that the contemporarydeathbed still has more than a few bugs.For all our dollars spent and efforts made, andall our talk of living wills and other advancedirectives, we’re often still missing the mark.Where do we fall short of providing thegood death, and what can we do to improve?Barnato and others at Pitt are starting toanswer these questions.Pitt’s Bob Arnold, a former presidentof the American Academy of Hospice andPalliative Medicine, says the good death hasremained elusive for a variety of reasons. Toname a few: Patients and families don’t knowto expect good palliative care, healthcareproviders haven’t traditionally been trainedto provide it, and health care in this countryis financed with an emphasis on acute ratherthan chronic illness.To address these issues, Family Hospiceand Palliative Care—one of the first hospiceprograms in Pennsylvania—and Pitt’shealth sciences schools jointly established theInstitute to Enhance Palliative Care in 2003.The institute educates healthcare providersabout palliative care, raises public awarenessabout palliative care availability, advancespublic policy supporting better care for seriouslyill patients, and conducts research intobest practices.“Twenty or 30 years ago there wouldhave been no one looking at this stuff,” saysArnold. “Now there’s a whole group of juniorinvestigators and researchers at Pitt whoare all really interested in focusing on theseissues.”David Barnard, who directs the Institute toEnhance Palliative Care and palliative care educationat Pitt’s Center for Bioethics and HealthLaw, says one of the bigger problems with thecontemporary deathbed is the way prognosis isoften communicated. Studies show that doctorstend to paint a brighter picture to patientsand their families than the doctors themselvesperceive—either consciously because they’reuncomfortable or unconsciously because thebetter doctors know their patients, the morelikely they are to be overly optimistic in theirpredictions. This leads to problems once apatient really starts to decline.As a member of the UPMC EthicsCommittee, Barnard has seen it countlesstimes: The patient has multisystem failureand has been on a ventilator for two weeks.The doctor calls and says, “The family doesn’tget it.” Barnard explains: “Too much timeis spent deciding which treatments to do,rather than getting to know the patients andwhat they want. The important question theyshould be asking patients is: ‘What characteristicsof life make it worth living?’”In 2001 and 2005, Barnard securedfour-year National Cancer Institute (NCI)grants—totaling about $1.75 million—toincorporate new palliative care offerings intothe curriculum. Palliative care training is nowavailable at all levels of instruction, fromclassroom to residency to fellowship.In one course, Barnard pairs first-year studentswith patients with life-threatening illnesses.They spend time together throughout thesemester. Medical student Yohko Shinozawa(Class of ’08), who took the class two yearsago, was assigned Mike Kolansky (not hisreal name), a bearded, tattoo-clad motorcycleenthusiast in his 60s. Kolansky had undergonea liver transplant, and, as a result of his immunosuppressantmedications, his kidneys began“Medical personnel, while pumping on the chests of the dying,have been asking themselves, ‘Why are we beating a dead horse?’”failing 10 years after the surgery.Each Saturday, Shinozawa sat with him forone hour of his 12-hour weekly dialysis regimenat the VA hospital.To Shinozawa’s surprise, the two didn’tdiscuss his illness much. “He was laid-back,always joking around,” she says. “He was veryfocused on living and making the most of hislife.” Since her semester in Barnard’s class,she has volunteered regularly for the palliativecare program.The institute also offers a two-year palliativecare fellowship that combines researchwith clinical care. First-year fellow ElizabethWeinstein (MD ’02, Res ’05) notes that whilemany palliative care fellowship programs arerun through oncology or geriatrics divisions,Pitt’s is part of the Division of GeneralInternal Medicine. “One of the things I loveabout Pitt is that we see such a broad rangeof patients.”Weinstein says that a feather in the program’scap is Arnold himself. “A couple ofweeks ago we were at a national meeting.Everyone was grabbing for five minutes ofBob Arnold’s time. ... But he always down-22 PITTMED

plays what he does. You wouldn’t realize he’sone of the heads of this new field.”Arnold worked with colleagues at theUniversity of Washington, Seattle, to createOncotalk, a four-day retreat funded by theNCI to train oncology fellows in communicationskills. (Oncotalk was featured in TheNew York Times in January.) In spring 2008,Arnold will begin a new retreat, funded by theJewish Healthcare Foundation of Pittsburgh,to train pulmonary and critical care fellows toconduct family meetings.Arnold says facilitating conversations withgroups of people in the middle of a highlyemotional situation is an acquired skill. “Youhave to practice. ... Often people will focusmore on the cognitive material rather thanthe emotional.”Barnato, who interned in general surgerybefore pursuing her career in research, canrelate. “We’d tell you about every aspect ofyour mom’s physiology, every organ system,and then we’d just end with a ‘We’re doingeverything we can.’ That was our form of afamily meeting.”One case from her internship workingin an ICU in another state stays with her. Itreminds her how patients and their familiescan be cut out of the decision-making process.After inserting bilateral chest tubes—anaggressive surgical measure known to helpin some cases of respiratory arrest—Barnatowas able to bring an 85-year-old womanback from a code blue. The patient was thentransferred to a long-term, acute-care facility,where she died a few months later.“We had amputated her feet and parts ofher lower legs,” says Barnato. “She was bedbound and on a ventilator. Her favorite thingto do was watch TV, and she wasn’t going tobe able to do that because she was now almostblind because of her diabetes.”While the patient awaited her transfer,Barnato approached her and asked about herwishes. Though she couldn’t speak, throughnotes and gestures the patient told Barnatothat this wasn’t what she wanted.Barnato was nervous about bringing itup but ultimately decided she had to. “Doyou know what my resident did?” she says.“He ordered a psychiatry consult. The psychiatristcame, saw her, and decided she wasdepressed. And he started her on—I’m notkidding—Prozac. ... It was very demoralizing,to say the least.”In a study published in Critical CareMedicine in 2004, Barnato looked at the finalhospitalizations of deceased patients acrossthe country, comparing the aggressiveness oftreatment. She found that in some geographicregions, the average ICU stay was much longerthan others. Since then, she’s found a lotof variation from hospital to hospital, ICUto ICU, and doctor to doctor. Recently, sheinterviewed staff members at 11 Pennsylvaniahospitals, asking them about end-of-lifedecision-making. She heard statements like,“This doctor tends to do this, but that doctortends to do that”—unsettling for Barnato.“You’d hope these decisions would be madeby the patient and the family [rather than thedoctor alone],” she says.Afew hours after Miller’s simulation,Arnold enters Smith’s room, introduceshimself, and squats beside the bedso that he’s almost looking up at Smith. If thiswere more than role-playing, he would haveroamed the halls looking for a chair—meetingthe patient at eye level is that important.Through a series of open-ended questions,Arnold gets the couple talking. They tell himall they know, including what’s going on withthe chronic illness they’ve been fighting allthese months.Arnold repeats it all back to them. “And sosome of this may be because of [the illness].Or it could be pneumonia. Or it could be ablood clot. And the problem right now is itlooks like he’s gotten a fair amount worse, andit could be because of any of those things. AndI guess the question is, Where do we go fromhere?” He pauses, then begins again, his pitchhigher, his timbre softer. “After you found outthat [the illness] was worse, had you guys evertalked about where you’d go?”They explain that they have a living will athome that says Smith “doesn’t want anythingextraordinary.”Arnold clarifies that they all agree on whatextraordinary means.Then he addresses Smith directly, askinghim if anything besides the shortness of breathis making him uncomfortable, what his wishesare, and whether or not he wants to be partof the conversation in the first place. “Somepeople when they’re sick don’t want to hear alot about the medical details,” he says, “andother people want to hear what’s going on.”He suggests medication that will easeSmith’s discomfort. He turns off the noisymachines that distract the couple from eachother, assuring them that Smith is still gettinghis oxygen. He asks if any loved ones or clergyneed to be there, and what kind of supportNancy Smith has. Again and again, he asksthem, “Questions?”Arnold is a palliative care specialist whohelped design this study, so he knows exactlywhat to do in this simulation. Still, listeningto him is inspiring—a reminder of what’spossible as American doctors become comfortableadding palliative care to their broaderdefinition of healing.For Shinozawa, the definition of the gooddeath has become more nuanced as she volunteersfor Pitt’s palliative care program.Some patients want somebody to talk to.Some like the silence but still want companionship.Some can’t tell you what they want,because they’re unable to speak or write, andit takes a lot of yes-or-no questions to understandtheir desires.And then there are the patients who simplywant to focus on living with an illness—likeKolansky the biker. “Don’t take life so seriously,”he told Shinozawa the day they met.“Take it as it comes.”Once, she asked, “Is there any one thingyou want to do before you die?”“Go on one last ride,” he said. He addedthat he didn’t want to burden his family witha funeral. “Sprinkle my ashes on my Harley,”he said, joking. “Take me cruising one moretime.”“Death isn’t easy to talk about,” saysShinozawa. “It’s not like after we take thiscourse we become experts on this. But I thinkit’s a good start.”■SUMMER 2007 23 21

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FEATURE45 YEARS OF DISCOVERY LATERINTERVIEW BY SHARON TREGASKISDEFININGMOMENTSThe University of Pittsburgh medical school’s Class of’62 trained in the shadow of giants—biochemist KlausHofmann, pathologist Frank Dixon, internist Jack Myers,Jonas Salk and Julius Youngner of the killed-virus polio vaccine,surgeons Henry Bahnson and Albert Ferguson. Molecular biologywas an emerging field, and even first-year students could contribute tothe explosion of knowledge. Nearly half a century after they earned theirdegrees, four members of the Class of ’62 recall moments that shapedtheir careers and reflect on the life of the physician-scientist, a professionsome have called endangered.Brooklyn’s SUNY Downstate Medical Center professor of medicineAlbert Braverman, a hematologist-oncologist, has investigated breastcancer treatment, thalassemia, and sickle-cell disease. Braverman’s creditsinclude medical publications as well as literary analyses of the works ofThomas Mann and Robert Frost. Director emeritus of the renal divisionat Brigham and Women’s Hospital Barry Brenner is the SamuelA. Levine Professor of Medicine at Harvard University. He authored thetextbook The Kidney and defined the role of the glomerulus in chronicFour standoutclassmates talkabout a life of discovery.from left:Albert Braverman,Barry Brenner,James Kushner,and John Hibbs. ILLUSTRATION | ROB KELLYSUMMER 2007 25

enal diseases. John Hibbs is DistinguishedProfessor of Internal Medicine and chief ofthe Division of Infectious Diseases at theUniversity of Utah in Salt Lake City, whereformer classmate James Kushner is theM.M. Wintrobe Distinguished Professor ofInternal Medicine and heads the Division ofHematology. Hibbs garnered a Nobel Prizenomination for teasing out the biochemistryof nitric oxide. Kushner serves as director ofthe University of Utah’s Center of Excellencein Molecular Hematology; he delves intogenetic disorders of iron metabolism.These far-flung old friends gathered thiswinter through teleconferences. Here we shareexcerpts of two recent conversations.PM: What do you remember of oneanother as students?Kushner: My most striking memory ofAlbert Braverman involves incredible glasswarebreakage during biochemistry lab. He smokedTurkish cigarettes.Braverman: Gauloise. My wife is Turkish,but I don’t smoke anymore.Brenner: Albert and I were in adjacentrooms on the eighth floor of Salk Hall. Havinghim as a next-door neighbor was one of thegreat enrichments of my young life. He carriedan aura of goodwill that spread to everyone hemet and touched.Hibbs: We would often eat together in thecafeteria at Scaife Hall and have these wonderful,free-ranging discussions, always intellectual.Brenner: On Friday nights, we’d go downto Cantor’s in Oakland. It was $2.95 a dinner.Not much wine was poured, but they did havewonderful food. Those dinners were probablythree hours.Braverman: I came to medical school interestedin psychiatry. Because of Barry, my interestturned to science. He was the first person Iknew personally who had an intellectual interestin science and clinical medicine. John had intelligence,breadth, moral rectitude, seriousness,and good humor. It was a tremendously enrichingtime.Brenner: John was tall, very handsome,casual in appearance. Never the type to interrupt,he’d just let you talk and then he’drespond. Jim was very smart, witty. Pitt was myfirst away-from-home experience. Right fromthe start, Jim, you were in an apartment.Kushner: I lived on the second floor of afuneral parlor on Negley Avenue. In the evening,I and my roommate—Eduardo Delgado(MD ’60)—would cruise through the salonsand, instead of supper, eat all the chocolatesthat were set out for the mourners.Brenner: But did you have any embalmingresponsibilities?Kushner: Barry, I remember you were veryfunny, with round glasses and an ability toincorporate knowledge at a tremendous pace.Medical school seemed very easy for you.Brenner: I spent that whole summer beforemedical school working in the post office. Theforeman told me, “You better do well in medicalschool because you wouldn’t have any futurehere.” I was motivated, having been cut offfrom this other opportunity.Braverman: I was a very successful messagerunner on Wall Street. That career wasopen to me.Kushner: Barry, you were commentingthat John was a casual guy. John is a hopelessromantic. He sees drama and romanceeverywhere, particularly in science. I rememberwhen he was first discovering the pathway fromL-arginine to L-citrulline and nitric oxide, andhow macrophages got activated. It was likelistening to the most wild-eyed guy in UnionSquare standing on a soapbox.Braverman: I remember John’s macrophagepaper. I had my doubts about the immunotherapyof cancer, and here I saw this paperin Science—and from macrophages and cancercame an overwhelmingly important discovery[the mechanism for formation of nitric oxide inthe human body] that was completely separate.Brenner: John should have received theNobel.Kushner: He couldn’t. He doesn’t havea tie.Brenner: I would not have guessed, fromthe four years we were in medical school, thatJohn Hibbs was destined for a career in basicscience. John, tell me why I missed it.Hibbs: When I was in medical school, Ididn’t do any science other than our laboratories—biochemistry,physiology, etc.—the smellsand the activity seemed far removed from clinicalmedicine and what we were learning fromthe textbooks and professors.Braverman: When did it change for you?Hibbs: Jim and I were both drafted whenwe were interns. There was a hemorrhagicfever epidemic that began in eastern Bolivia,and I volunteered to go down and work withsome scientists from the NIH. It was physicaladventure, but the research turned out to beintellectual adventure.There’s nothing more stimulating than workingin a basic research laboratory, once you learnhow to use the scientific method. It’s so powerful,so basic, and it’s the rigorous testing of knowledgethat separates science from superstition, fromideology, theology. It doesn’t produce absolutetruth, but it gets us closer. There’s so much excitementin seeing things for the first time.Kushner: See what I mean about him being aromantic? I found my transforming event in thepathology laboratory experience with Frank Dixon[the pathologist who showed that the immuneresponse could cause disease].Brenner: One of my interviewers was [molecularbiochemist] Harold Segal. Not only did heset in motion my acceptance letter, but with itcame an invitation to start work in his laboratoryon the day I started medical school. I sent off amanuscript in January of my first year. It has myname as B. Morton Brenner. I went through thisaffectation that lasted only as long as that paper.Someone said to me, “Oh my god. I’ve been callingyou Barry. I should call you Morton.” I said,“Never mind, I’ll change my name back.”PM: What was Pitt like then?Braverman: This was the decade in whichmolecular biology came into being. The microbiologycourse was where we heard about tRNA andmRNA and all the things that were coming outthen, where we got the foundation.Brenner: I think it was the virology component,Al. Julius Youngner was giving these lectureswhere it was as if he would read a paper and thefollowing week, the material was incorporated intothe lecture. There was almost no dwell time.We got to do that serum sickness experimentunder [pathologist] Joseph Feldman’s guidance.Braverman: Low titer, medium titer, hightiter. Medium titer did it.Hibbs: The School of Medicine had gatheredtogether a unique group of human beings bothin basic science and the clinical years. It was likeAthens during its heyday or Florence during theRenaissance.Braverman: One person was more uniquethan the others. [Department of Medicine chair]Jack Myers was a force in Jim Kushner, I can attestto that.Kushner: As a physician, a clinician, everythingabout me—my whole personality—wastransformed by him. He knew his own mind. Hehad the courage to think through a clinical situation.And he really believed that doctors had totake responsibility to do things that were difficult.Brenner: I remember presenting to Jack atthe bedside, at 10 o’clock in the morning. Youworked up the patient the night before, finishedaround midnight, stayed in that little PresbyterianHospital library, read everything you could aboutthe diagnosis you were entertaining. This year,on my first day of general medicine, I had a kid26 PITTMED

“It was like Athens during its heyday or Florence during the Renaissance.”tell me about one of his 22 admissions the nightbefore, but he had a clipboard in front of him.He’s reading to me the age, the name, the historyof the present illness. I said after 12 seconds, “Putyour notes down. Just tell me about the case.” Hecouldn’t. I said, “We will have no more roundstoday. Tomorrow, whoever presents better knowthe case, not the notes. Show me that you’vethought about this, that there’s been some integrationof the information.” I was brought before thedepartment chairman as being out of line.Kushner: That was Jack Myers speakingthrough Barry Brenner.PM: What else stood out?Brenner: The attendings we had were chiefsof service. Today the attendings—I only know itfrom where I work—are people who are out oftheir training a year or two, or they’re hospitalists.Braverman: I had [as attendings] GerryRodnan, head of rheumatology; Abe Braude, headof infectious disease; Ted Danowski, one of theworld’s premier diabetologists. And that was therule; it wasn’t that I drew the lucky three. Todayyou would see no equivalent people—almostnone—in a similar role.PM: What is your personal process ofdiscovery?Kushner: The idea-development process thatleads to the experiments, the manuscripts, and thegrants comes from interaction with the people inyour lab, your colleagues, your mentor. The inspirationfor discovery comes from constant reading,constant observing, and constant interaction.Hibbs: Science is a very communal activity,and we interact on many dimensions. We’reexposed to the ideas and the work of many differentscientists, of many different nationalities. Allof these go into the mix.Brenner: For me, everything came at the endof the long day, in the quiet of the night, by replayingthe tape that I went through in my wakinghours. I have not spent a night since I was 25 yearsold without index cards on my night table. I go towork in the morning and just follow the leads ofthat digestion or reanalysis from the night before,thinking through how I should change [a study],do it differently. The data drive the steps day inand day out. Nothing else matters.Braverman: Young people have one greatadvantage: Instead of index cards, there’s a databaseprogram. If I have 10,000 notes and 700 to800 patients on a program, I can ruminate over thedata, look at it from different perspectives. It makesit so much easier, so much more convenient.PM: How would you advise people aspir-ing to careers like yours?Brenner: The name of my game was toamass an enormous number of experimentalmodels, to make measurements repeatedly, tothe point where I could pretty much fashionthe discipline. I didn’t have to look over myshoulder very much and didn’t have the stressof competition. After 25 years, I could relyto a large extent on younger colleagues I hadtrained. And that gave me time and the freedomto extend myself into other areas.Kushner: Pick the right mentor. The key tobeginning a career as an academic person is toget a career development award. It assures youprotected research time. It takes a mentor totell you how to write the grant, how to organizeyour thoughts.Hibbs: I still approach basic biology like achild, with this almost naïve enthusiasm.Brenner: If you’ve really excelled in yourclinical training, then go into a basic laboratoryand find that you know nothing—thatthe technicians are dominant, and you’re justlearning how to mix solutions. When you gothrough that year depressed because nothingworks, you’re breaking glassware, that’s whenthe mentor has to help you work on somethingwhere you can be successful.PM: What are the prospects for thephysician-scientist?Brenner: The personal reward of a career ininvestigative medicine is second to none.Braverman: My wife understood howimportant my work was to me, and we decidedthat despite the financial opportunities of privatepractice, we were going to stick with whatI was doing in academic medicine. I’ve neverregretted it.Kushner: People who choose this pathreally have to have a terrific desire, a burninginterest. And nothing will satisfy them otherthan testing their ideas and learning how to dothe tests. I don’t know how our partners put upwith us. I don’t go home very often.Hibbs: If you’re really doing somethingthat’s true investigation—and the more basic itis, the more risky it is in terms of really succeedingin uncovering new knowledge—there is thisinherent risk that makes it very uncomfortable,but true adventure. Balancing this with clinicalwork can be tough.Kushner: John, I remember a time whenFrançoise was urging you to spend more timeat home. I came to your house, and you hadmoved part of your laboratory to the house.You had a microscope setup next to the living room;you had plates; and youwere working from home.Brenner: That’s not what she had in mind.Hibbs: I realized early on that I had to giveup something, and what I gave up is academictravel. That way I could be a presence in myhome as a husband and as a father.Braverman: I used to take the kids to thelab and on rounds when they were young. Theyknew I wanted to be with them, and they hadsome notion as to what was going on. That wasimportant.PM: How do you feel about the prospectof retirement?Brenner: I hate to confront it, which is whyI tend not to. I spent 30 years doing mostlyanimal-oriented research. Then some very largeclinical trials. Now I find myself in epidemiology,which I never would have guessed 20 yearsago would have engaged me. I see my careerjust continuing to evolve. I pay less attention tothe clock, with the hope that if my health staysgood and my head stays reasonably good, thiscould continue for many years to come.Hibbs: In a year or so, good lord willing,there will be time to do some other things—readphilosophy and literature, spend time in Francewhere my wife is from, walk in the WasatchMountains. We recently solved a major conceptualbarrier in our research. Finishing this mayopen a new area for people to investigate, andI’ll be able to stop with a success.Kushner: I’ve got some tasks to finish, toensure the future of the people who depend onme and on whom I depend to be productive.It’s very hard to stop doing something you reallylike to do. We finally figured out the mechanismcausing a type of porphyria. We have alovely manuscript in PNAS [Proceedings of theNational Academy of Sciences] now describingwhat goes on in the liver cell. And I’ve becomea crystallographer in my old age.Braverman: There are so many things I cando, that I want to do. But the one existentialreality—I think we can all say—I stronglybelieve: We’ve had damn good lives. We’veenjoyed our lives. They’ve been fulfilling, productive.That’s why I don’t really worry aboutthe onset of age. I feel I can’t stop because I’llend up depressed if I lose the things I love somuch. It is a young man’s job. I’m getting up at5 in the morning to hear night-phone admissionsin Brooklyn, and it’s getting to be a littlehard. But I just can’t stop.Brenner: We’re the four horsemen—hopefullynot of the apocalypse.■SUMMER 2007 27

28 PITTMED

FEATUREENGINEERING CARDIAC TISSUEBY MELINDA WENNERTELLTALE HEARTS,AND VEINSCOURTESY BIOMATERIALS, 27, COURTNEY T, SACKS MS, STANKUS J, GUAN J, WAGNER W, 3631-3638, © ELSEVIER 2006.How do you mend abroken heart? Therapiesinvolving synthetic cardiactissue don’t boast reliablygood outcomes. Buta new material designedby Pitt bioengineerslooks promising. One keyto its design, say WilliamWagner and MichaelSacks, is how you alignthe tissue fibers. top:Close-up of polyurethanefibers in a random alignment.bottom: The fibershere mimic the smooth,coordinated alignment ofcardiac tissue.Patrick Fraizer’s heart was the size of a football. He didn’tknow that, of course, or he wouldn’t have driven all theway from his home in Fort Wayne, Ind., to Pittsburgh. Hewasn’t feeling as peppy as usual, but that’s why he was making the tripin the first place. Fraizer, a kind man with a ruddy face and enormousgrin, had suffered two heart attacks in the past nine years. He wasplanning to meet with Pittsburgh cardiologists about an experimentalcardiac therapy. He didn’t, however, know that things were as bad asthey were.When Fraizer arrived at the University of Pittsburgh Medical Center,doctors performed a routine catheterization to take a virtual snapshot ofthe condition of his heart. Then he and his wife, Mary Fraizer, waitedaround for the verdict. He was half-expecting to be sent back home.“We don’t think you can make it to the door,” the doctors told himinstead. They said it was a miracle that Fraizer was even alive—he hadso much scar tissue on his heart from his previous heart attacks that hisSUMMER 2007 29

heart was barely functioning. Worse, two of hiscoronary arteries were fully blocked and anotherwas disastrously close. The experimentaltherapy was a no-go. The doctors said insteadthey had to perform a much riskier open heartsurgery—immediately.That’s when they discovered that his hearthad swelled to the size of a football. Fraizer’sprevious heart attacks had, through the years,caused part of his heart muscle to balloon out.Often, the part of the heart that is starved ofoxygen during an attack can become so damagedthat it cannot do the work it used to do.The rest of the heart tries to make up for it,yet it can’t always compensate. So the damagedpart of the heart responds by thinning,ballooning, and stiffening. These reactionsreduce the muscle’s efficiency further and canlead to heart failure—something that Fraizerhad been flirting with for years without evenknowing it.While Fraizer was having his heart resculptedin the operating room, William Wagner andcolleagues were several blocks away exploringhow to prevent the need for such operationsin the first place. Wagner, the deputy directorof the University of Pittsburgh–UPMCMcGowan Institute for Regenerative Medicine,is a tissue engineer and Pitt professor ofsurgery, bioengineering, and chemical engineering.Along with Pitt colleague MichaelSacks, William Kepler Whiteford Professorof Bioengineering, Wagner oversees the developmentof a biodegradable heart patch thatmay one day prevent the long-term cardiacdamage that Fraizer and others suffer afterheart attacks. Wagner and Sacks’ work was recognizedby Scientific American as among the 50most outstanding acts of leadership in scienceand technology in 2006.Reportedly, heart tissue has been extremelydifficult to engineer because of its mechanicalproperties. It is strong, yet flexible, and is moreeasily stretched in one direction than another,depending on the direction in which its fibersare aligned. In addition, the body is sensitive tothe introduction of foreign materials that don’tquite match heart tissue’s natural properties.In his office, Wagner is surrounded by oldjournal issues, images of blood vessels, a whiteboardon which someone has scribbled circuitdiagrams and graphs, three cacti (remnants ofa youth spent in Phoenix), and numerous photosof his two young boys. Someone wanderingin might wonder whether he is a scientist oran engineer, a surgeon or a chemist. Wagnerthinks of himself as a translator between theworlds of engineering and medicine. Throughthe years that has meant working closely withpatients, doctors, and other types of scientists.“The way I describe it is as engineeringapplied to address cardiovascular disease,”Wagner says of his work.Engineering cardiac tissue in the labrequires expertise in many areas—mechanicaland materials engineering, chemistry, molecularbiology, immunology, and surgery, to namea few. Pitt stands out, observers say, becauseit has established a cadre of experts who workcohesively together.“That’s really how high-impact science isbeing done nowadays,” Wagner says. “It’sbeing able to assemble teams of experts whereyou have world leaders in different areas comingtogether and hashing out ideas.”“They have really made things happen,”says Kim Woodhouse about Pitt’s cardiacbioengineers. Woodhouse is a professor ofengineering and applied chemistry at theUniversity of Toronto. The Pitt team is pragmatic,synergistic, and creative, she says, andthis combination puts them right “at the leadingedge.”Wagner first became interested in applyingengineering to medicine when he was in graduateschool for chemical engineering at theUniversity of Texas at Austin. One day, whenlistening to an engineering professor talk abouthis work on blood clots, Wagner suddenly sawhow the engineering science that he’d learnedas an undergraduate could be applied to thehuman body.“I immediately knew that’s what I wantedto do,” he says.He graduated with a PhD in chemical engineering,after having spent many a Saturdayat the Texas Medical Association Library,slouched over medical journal articles. ThenWagner got an unexpected call from a surgeonat the University of Pittsburgh looking to hirea postdoctoral fellow to study blood clots andartificial hearts.“And I’m thinking, Pittsburgh? I’m fromArizona,” says Wagner with a laugh. Nevertheless,he visited.“Within a couple of meetings with people,I realized that it was kind of like Mecca,” herecalls. The problems he had only seen onmicroscope stages or in library cubicles inTexas were right in front of him at Pitt, havinga “very real impact on patients every day,” hesays. He accepted the position.At that point, Wagner wasn’t quite readyto step up to the role of translator—he was,literally, still learning the language of medicine.“I knew a lot of the terms, and I’d read themdozens of times,” he says, “but I’d never actuallyheard them pronounced!” As he immersedhimself, he started noticing an interesting trend:Some medical terms were oddly vague, and thereason for this, he realized, was that no onereally understood the processes they were tryingto describe. That, he thought, was a hole thatengineering could help fill.Wagner, along with Michael Sacks, a PhDbiomechanical engineer with a dry sense ofhumor and an astute eye for detail, began closelystudying the mechanics of cardiac processes, anarea Sacks first started researching in graduateschool at the University of Texas SouthwesternMedical Center at Dallas. The heart can bethought of as a machine, and Wagner and Sackswanted to understand it inside and out so thatthey could, in a sense, reverse-engineer parts ofit. Wagner and Sacks realized there was a hugemedical need for engineered cardiac tissue.Other bioengineers have typically used materialsthat poorly mimic the properties of cardiactissue—so Wagner decided it was up to his teamto develop something better.The engineers imagined developing a cardiacpatch that could help damaged hearts repairthemselves. This patch would work best, theytheorized, if it could mimic the types of temporaryscaffolds the body makes on its own allthe time.“When you cut yourself, you make a clot,and then you put a temporary scaffold in there,”Wagner explains. Then special immune cellsarrive, release enzymes that help the tissue regenerate,and clear the temporary scaffold away.But when the heart gets injured during a heartattack or because of other defects, it might notbe able to repair itself. Instead, it might respondthe way Fraizer’s heart did—by ballooning out,which causes further problems and makes theheart even less efficient. Wagner and his teamthen wondered whether it would be possible tocreate a synthetic scaffold that, if applied to theheart within a few weeks of a heart attack, couldallow the heart to repair itself.They went to work. One of Wagner’s postdoctoralfellows, Jianjun Guan, created a polyurethanematerial that was nontoxic, highlyelastic, strong, and biodegradable. Polyurethaneis the stuff of seat cushions, and Wagnerexplains that, like a good cushion, the materialis strong yet flexible, able to bounce backafter being compressed or stretched. His teamfound ways to manipulate the material so thatit stretches more in one direction than the30 PITTMED

ABCDCOURTESY D. VORP AND M. EL-KURDIDavid Vorp uses material developed in Wagner’s lab to keep veins from hardening when usedas arterial grafts: A) Vein with girdle. B & C) Polymer attaches to vein. D) Interior of veinremains intact.other—just like real cardiac tissue—and so thatit can degrade at different rates after cominginto contact with particular bodily enzymes.The team found ways to make the materialrelease growth factors to promote cell growthand differentiation. All the better, the materialis easy to make.“An undergraduate chemistry major couldbe taught to do it,” Wagner says.At the same time, Sacks studied the mechanicalproperties of heart tissue. How would asynthetic patch need to behave in order to closelymimic real cardiac tissue?, he wanted to know.Wagner collaborated with investigators workingwith stem cells—including Pitt’s JohnnyHuard, who is a PhD and the Henry J. MankinProfessor of Orthopaedic Surgery Research,and assistant professor of surgery Amit Patel,an MD—to eventually “seed” or embed thesynthetic scaffold with patient cells that couldlater be coaxed into developing into functionalheart cells. Wagner and Sacks imagined a seededpatch that could be sutured onto a person’sheart—not a particularly invasive procedure,because the heart does not need to be cut—andrestore working function to the muscle.While developing their überpatch, Wagner’steam made a serendipitous discovery. Theywere testing the effects of a patch on rats thathad experienced recent heart attacks when theteam found that even without stem cells, thepatch improved heart performance.“That’s a lot more attractive and a lotcloser to clinic than messing around withstem cells,” Wagner says. A plain patch wouldnot have to undergo as much testing forapproval by the FDA, he says, and it could beimplanted without first having to harvest cellsfrom the patient.That the patch worked well by itself wasunexpected, but Wagner has some ideas as towhy. First, the patch acts like a kind of girdle,he notes, preventing the injured heart fromballooning out as it tries to heal. This keepsheart cells healthier, so they are less likely todie. Second, as the body’s immune cells comeinto contact with the patch, they might releaseenzymes that help the heart heal faster.In the past, engineers have designed heartpatches out of permanent materials like Goretex.If doctors use Gore-tex patches to treatchildren born with heart defects, “the kid’sgoing to grow and [the patch is] not going togrow, so they’re going to have to go in and keepchanging it out in many instances,” Wagnersays.In older patients, Gore-tex patches appliedto help support the weakened heart wall aftera heart attack present other problems. In thesecases, surgeons must open the heart and placethe Gore-tex patch on the inside surface.Wagner’s patch does not require such riskysurgery; it is fastened to the outside surface ofthe heart, a less invasive procedure.Blood contact with foreign materials cantrigger clot formation and these clots canbreak free and cause strokes. So patients withGore-tex patches often have to take bloodthinners. But the Pitt patch avoids bloodcontact and, by design, clotting and the needfor blood thinners.The Pitt team has also figured out a way tomanufacture tissue scaffolds quickly, both withand without seeded cells. This breakthroughis important clinically and could have implicationsbeyond a cardiac patch. The methodcould be useful for engineering other thin,SUMMER 2007 31

elastic tissue in the body, such as bladders, aswell as tube-like structures like the urethra andesophagus.Although Fraizer’s surgery went well—andhis hospital recovery was sweetened uponlearning that he would soon be a grandfatherfor the first time—his heart will forever beweak. “If I see 65, I’ll be a blessed man,” hesays, now almost 61.Perhaps 10 years from now, if all goes wellin the laboratories at McGowan, a patientwith Fraizer’s heart condition will be able tolive a lot longer than that. Wagner and Sackswill be testing the patch, with and withoutstem cells, in large animals and humans overthe next few years.After his second triple-coronary-bypasssurgery in 2002, then-43-year-oldDouglas Laney was told by his doctorsthat there was nothing more they coulddo. Even two triple bypasses hadn’t fixed hisproblem permanently. The average lifespan ofa vein graft is seven to 10 years—a lifespanthat diminishes with every additional bypasssurgery. So Laney was scared, especially whenhe began having chest pain again last year.“I didn’t know what to do,” he says. But hedid do something: He got a second opinion.After performing a catheterization, the doctorstreating Laney visited him in his recoveryroom. Laney was waiting anxiously, afraid ofwhat they might tell him. But the doctorsdelivered good news: They were willing to takethe chance that his previous doctors refusedto take. They were willing, they said, to try toperform another bypass.“I experienced probably every human emotionwithin five minutes,” Laney says. “I wasoverwhelmed with joy.”In patients with clogged arteries, bypassesusually fail because the replacement veins,which are often nonessential veins taken fromanother part of the body, aren’t up to the job.Veins are used to living “a pretty cushylifestyle,” according to Pitt vascular engineerDavid Vorp, and are not prepared for thedemanding arterial environment. Veins areused to low blood pressure and low flow, andthey don’t feel the pulsations of the heart.Arteries, on the other hand, have higher bloodflow, higher shear stresses, and they pulsatebecause of their proximity to the heart. Sowhen veins from the leg are plugged into thearterial environment, they tend to panic.“They say, ‘Wait a minute, we’re veins,we’re not supposed to be experiencing this,’”says Vorp, an associate professor of surgery. Heexplains that a vein implanted into the arterialenvironment assumes that it is injured, so itimmediately begins trying to counteract theproblem. It does so by thickening. As it thickens,however, the canal also begins to narrow.Sound familiar?“You end up having the exact same problemas you had before. You have narrowingand clotting off of the blood flow, and that’sone of the primary failure mechanisms of veingrafts,” Vorp says.That’s exactly what happened to Laneyafter his first two bypasses—his grafts failed.Although he was understandably nervousabout going in for another triple bypass, hesays that, psychologically, it was easier the thirdtime around. “This time, I had reached a pointof acceptance that what was going to happenwas going to happen,” he says. Luckily, thesurgery was a success; even so, he can’t be asactive as he once was, though he likes to helpout with his church and do other volunteering.And there is always the fear that the graftscould fail again.Vorp, who is soft-spoken and sports a reddish-goldenbeard, hopes that his collaborationwith Wagner will eliminate the need forrepeat bypass surgeries by making implantedveins stronger. If the vein to be used in bypasssurgery is first wrapped in a biodegradablepolymer material like the one developed forWagner and Sacks’ cardiac patch, it may notthicken as much upon exposure to its newenvironment. Then, after a few days perhaps,the wrap degrades, allowing the vein to slowlyadapt to its new harsh environment. The veingirdle has a patent pending.Vorp describes himself as being “born,bred, raised, trained, and differentiated, if youwill, in Pittsburgh.” What actually “differentiated”him from a typical mechanical engineerinto a bioengineer was a class he was requiredto take as a Pitt student. “This silly littlecourse, that I tried to put off and tried to getout of taking, pretty much changed my life,”he says. In it, he was required to write a reporton how mechanical engineering impacts society.When he explained this to his girlfriend atthe time, who was in dental school, she notedthat mechanical engineering plays a big part indentistry. That piqued his interest.“I went to the library, and I stumbledacross two journals. One was the Journal ofBiomechanics, and the other was the Journal ofBiomechanical Engineering. I just was devouringthese, and I thought it was the coolestthing,” he recalls.At the time, Pitt didn’t have a bioengineeringdepartment, but Vorp was able to get aresearch position after graduation working withbioengineer Harvey Borovetz, who was then inthe Department of Surgery. That’s where Vorpdeveloped his expertise in vascular bioengineering.He also worked closely with patients anddoctors in the artificial heart program.The “bread and butter” of Vorp’s work thesedays is studying the mechanics of the abdominalaortic aneurysm, a condition in which the largeblood vessel supplying blood to the lower bodybecomes abnormally large. Vorp is developingnoninvasive ways to predict which types ofaneurysms are at risk of bursting.He also is trying to develop fully syntheticarteries using tiny biodegradable polymer-basedtubes that can be seeded with stem cells. Hewants to coax the stem cells to develop into vascularcells. Then, as the polymer breaks downafter implantation, the cells would take over andcreate a complete blood vessel. If his team canfind a way to do this, it will have become thefirst to create a successful artificial artery.Asked how long it will be before all of theseprocedures, including the vein girdle, are testedin humans, Vorp laughs, saying, “It’s funny, itseems like every time someone asks me how faraway we are from clinical translation, I say fiveyears. I said that 10 years ago, and I said thatfive years ago.” Then he smiles. “This is probablythe first time that I can think about it andbelieve that it’s going to be less than five years.”Wagner and Sacks are also pursuing otherprojects. For example, they are developing anengineered heart valve using the same polyurethanematerial as the patch. Although it will be ayear or two before they begin testing it in smallanimals, the mechanical properties of their engineeredvalve seem to match natural valves.The value of life has become even clearerfor Fraizer since his surgery. Althoughhis heart is no longer as big as a football,metaphorically, it still seems to be. He pours asmuch of it as he can into his 1-year-old granddaughter,BreAnna, whom he babysits everyday. He admits that he spoils her a little, but,he says, that way she will always know she onlydeserves the best.“Things really do blossom out of tragedy,”he says. “I absolutely love being around thisgirl.”“What we are doing,” says Vorp, reflectingon his work one day recently, “is really trying tomake life happen.”■32 PITTMED

MATCH RESULTSCLASS OF 2007There was a lotof celebrating asgraduating studentslearned wherethey’d be doingtheir internshipsand residencies.KAPELEWSKI / CIDDEANESTHESIOLOGYEsper, StephenUPMC Medical Education ProgramGabriel, JesseWestern Pennsylvania HospitalGrable, BenjaminUPMC Medical Education ProgramKwok, GarrickUPMC Medical Education ProgramLin, CharlesUPMC Medical Education ProgramMcCray, JustinUPMC Medical Education ProgramVictor-Vega, CassandreUniversity of Rochester/Strong Memorial Hospital,N.Y.Webber, AudraUPMC Medical Education ProgramZehnaly, AlenHarbor – UCLA Medical Center, Calif.DERMATOLOGYCarlos, CaseyHospital of the University of PennsylvaniaKwon, SoonyouUniversity of Maryland Medical CenterPatel, ShailyUniversity of Chicago Medical Center, Ill.DIAGNOSTIC RADIOLOGYGage, KennethJohns Hopkins Hospital, Md.Ho, AndrewUniversity of Chicago Medical Center, Ill.Kantartzis, StamatisUPMC Medical Education ProgramPatel, AmishHenry Ford Health Science Center, Mich.Seo, Su-hunAllegheny General Hospital, Pa.Whetstone, JosephOregon Health & Science UniversityEMERGENCY MEDICINEAblordeppey, EnyoBarnes–Jewish Hospital, Mo.Barton, JosephUC Davis Medical Center, Calif.Brown, EmilyBrigham & Women’s Hospital, Mass.Cochran, KristinBeth Israel Deaconess Medical Center, Mass.Connors, MeganStanford University Programs, Calif.Frattaroli, GregoryChristiana Care Health Services, Del.Pousson, AmeliaChristiana Care Health Services, Del.Rivenburgh, MatthewUPMC Medical Education ProgramRoberts, LindsayBeth Israel Deaconess Medical Center, Mass.Shetty, PranavHarbor–UCLA Medical Center, Calif.Skolnik, AaronBrigham & Women’s Hospital, Mass.Sokolowski, DevinRhode Island Hospital/Brown UniversityTarr, CarlyAllegheny General Hospital, Pa.Terrano, JenniferChristiana Care Health Services, Del.Wheeler, MatthewUPMC Medical Education ProgramFAMILY PRACTICEBarragan, LorenaMacNeal Memorial Hospital, Ill.Butela, HeatherOregon Health & Science UniversityFarahi, NargesUniversity of California, San FranciscoImler, ErinUPMC St. MargaretLeBlanc, KarenMemorial Hospital of Rhode Island/Brown UniversityLewis, AlisonBeth Israel Medical Center, N.Y.Manuel, VladimirUCLA Medical Center, Calif.Marshall, KristaUPMC St MargaretMcDowell, MarkBeth Israel Medical Center, N.Y.Miller, BrianUPMC St. MargaretPhelps, TracyUPMC St. MargaretSullivan, BrianScripps Mercy Hospital Chula Vista,Calif.Wick, MatthewWashington Hospital, Pa.INTERNAL MEDICINEAgcaoili, Cecily MarieUniversity of Maryland Medical CenterBrahmanandam, VikramBoston University Medical Center,Mass.Cheung, SoniaUniversity of California, DavisDe Vito, NicholasThomas Jefferson University, Pa.Falke, EricYale–New Haven Hospital, Conn.Gascon-Flores, AvegailHarbor–UCLA Medical Center, Calif.Kagan, SethSanta Clara Valley Medical Center, Calif.Koprucki, MichaelUPMC Medical Education ProgramMastalerz, KatarzynaOregon Health & Science UniversityMazzarella, DaraUniversity of Michigan Hospitals–Ann ArborMehta, MonaNew York University School of MedicineNayeb-Hashemi, HamedUCLA Medical Center, Calif.Pan, StephenStanford University Programs, Calif.Rachakonda, VikrantBarnes–Jewish Hospital, Mo.Rao, ShivdevUniversity of Michigan Hospitals–Ann ArborRavella, ShilpaBoston University Medical Center, Mass.Sabatini, MichaelUPMC Medical Education ProgramSawatsky, AdamMayo School of Graduate Medical Education, Minn.Singh, DivyaUniversity of Chicago Medical Center, Ill.Staub, BrianUPMC Medical Education ProgramStephenson, LydiaUPMC Medical Education ProgramSwan, ChristopherUniversity of California, San FranciscoTan, RoderickUPMC Medical Education ProgramTu, BenjaminJohns Hopkins Bayview Medical Center, Md.Williams, VonzellSUNY Health Science Center–Brooklyn, N.Y.INTERNAL MEDICINE—PEDIATRICSMcCormick, AndrewUPMC Medical Education ProgramINTERNAL MEDICINE —PRELIMINARYWolski, MichalUPMC Medical Education ProgramINTERNAL MEDICINE—PRIMARYDolan, BrigidBrigham & Women’s Hospital, Mass.INTERNAL MEDICINE—WOMEN’S HEALTHOsterholzer, ChristineUPMC Medical Education ProgramTilstra, SarahUPMC Medical Education ProgramMAXILLOFACIAL SURGERYNorbutt, CraigUPMC Medical Education ProgramNEUROLOGICAL SURGERYBonfield, ChristopherUPMC Medical Education ProgramGologorsky, YakovMount Sinai School of Medicine, N.Y.NEUROLOGYLui, AlbenUniversity of California San Diego Medical CenterShtrahman, MatthewUCLA Medical Center, Calif.OBSTETRICS/GYNECOLOGYBrannon, RyanDrexel University College of Medicine, Pa.Ching, MelissaWhite Memorial Medical Center, Calif.Gerschultz, KellyUPMC Medical Education ProgramJones, CandiceWalter Reed Army Medical Center, D.C.Krajewski, ColleenCase Western/MetroHealth Medical Center, OhioLandis Lewis, DeborahUPMC Medical Education ProgramO’Neill, EricaUniversity of North Carolina Hospitals, Chapel HillPhillibert, DonaldStony Brook Teaching Hospitals, N.Y.Sakamoto, SaraUPMC Medical Education ProgramOPHTHALMOLOGYHealey, JeffreyUPMC Medical Education ProgramIsawi, HannyPennsylvania State University–HersheyKim, GeneEmory University School of Medicine, Ga.Stuber, ChristiannaUniversity of California, DavisORTHOPAEDIC SURGERYFrank, MatthewUMDNJ–New Jersey Medical SchoolHeffernan, MichaelUniversity of Massachusetts Medical SchoolStarman, JamesCarolinas Medical Center, N.C.VanBeek, CorinneNew York–Presbyterian Hospital–ColumbiaWiegand, LauraHospital of the University of PennsylvaniaOTOLARYNGOLOGYDhanisetty, ShilpaUPMC Medical Education ProgramJabbour, NoelUniversity of Minnesota Medical SchoolKim, HaenaNorthwestern McGaw/NMH/VA, Ill.MacKechnie, CherylUPMC Medical Education ProgramRodriguez, KennethUPMC Medical Education ProgramPATHOLOGYGilbert, ChristopherUPMC Medical Education ProgramMiller, JenniferUPMC Medical Education ProgramPEDIATRICSBerger, LorettaDartmouth–Hitchcock Medical Center, N.H.Christ, LoriChildren’s Hospital of Philadelphia, Pa.DiCaprio, HeatherBaylor College of Medicine, Houston, TexasEhrlich, LoriChildren’s Hospital of Philadelphia, Pa.Ghanem, LouisChildren’s Hospital of Philadelphia, Pa.Hong, BorahUniversity of Washington Affiliated Hospitals, SeattleLee, VivianMiami Children’s Hospital, Fla.Min, StuartChildren’s Hospital of Los Angeles, Calif.Ogonowski, JulieUPMC Medical Education ProgramPinto, RupalSt. Christopher’s Hospital, Pa.Sabnis, AnimeshNorthwestern McGaw/CMH, Ill.Steinhauser, SarahCase Western/University Hospitals, OhioPHYSICAL MEDICINE &REHABILITATIONGleason, LisaVA Greater Los Angeles Health System, Calif.Groh, MeganMount Sinai Hospital, N.Y.PLASTIC SURGERYDudas, JasonBarnes–Jewish Hospital, Mo.Rogers, CarolynUniversity of Wisconsin Hospital and ClinicsPSYCHIATRYManchandia, AvinashUCLA Semel Institute for Neuroscience, Calif.Marcsisin, MichaelUPMC Medical Education ProgramPaleos, K. CaseyNew York University School of MedicineShaw, BillinaUniversity of Maryland Medical CenterStoklosa, JosephMassachusetts General HospitalPUBLIC HEALTHMarino, NatalieUniversity of Pittsburgh GSPH(Pursuing Master of Public Health)RADIATION ONCOLOGYShen, XingleiThomas Jefferson University, Pa.SURGERY—GENERALCavallo, JaimeBarnes–Jewish Hospital, Mo.Colovos, ChristosCedars–Sinai Medical Center, Calif.Hoffman, MarcusUPMC Medical Education ProgramHowell, GinaUPMC Medical Education ProgramMoran, ColleenShands Hospital, University of FloridaNaiditch, JessicaNorthwestern McGaw/NMH/VA, Ill.SURGERY—PRELIMINARYWin, KarenMercy Hospital of PittsburghTRANSITIONAL MEDICINEFeng, MatthewUPMC Presbyterian ShadysideWegner, RodneyUPMC Presbyterian ShadysideUROLOGYAkhavan, ArdavanMount Sinai Medical Center, N.Y.Mori, RyanCleveland Clinic Foundation, OhioOgagan, P. DafeUPMC Medical Education ProgramSUMMER 2007 33

ATTENDINGRuminations on the medical lifeMajta Seiden, shortly before she was sentwith her family to the concentration camp atBelzec, PolandSCIENCEAND MURDERHOW DOCTORS LENTSUPPORT TO GENOCIDEBY REID R. FRAZIERHer name is Majta Seiden. In the photograph, she’s 18 years old. The Seidenswere among 106 Jewish families studied in the spring of 1942 in Tarnow,Poland, by a team of Austrian anthropologists researching the “race biology”of Polish Jews. Its purpose, the study’s lead author wrote, was to form the “basis for relocationand new settlements” of Jews in the Reich. In the course of 10 days, the anthropologistsmeasured noses, skulls, and torsos. They recorded the color of eyes, skin, and hair. They tookfingerprints, handprints, and detailed family medical histories. They drew blood.The researchers took photos of Majta, her parents, and her two younger brothers. Each ofthe subjects posed for photos from three angles—in profile, at 45 degrees, and facing the cameradirectly. When Majta faces the camera, her lips are upturned at the corners, ever so slightly.A few months after this photo was taken, by June of 1942, more than half the Jewishpopulation of Tarnow had been sent to the concentration camp in nearby Belzec. Historiansbelieve the Seidens would have all died in the camp.Viewed on a museum wall decades later, the Seiden photos are a stark example of the humantoll of Nazi Germany’s eugenics movement. The Nazi obsession with genetics rationalized masssterilization and euthanasia of the mentally ill and otherwise disabled and gave “intellectual” andmaterial support to the Holocaust. “Deadly Medicine: Creating the Master Race”—a documentaryexhibition at The Andy Warhol Museum this winter sponsored by UPMC and organized by34 PITTMED

U.S. HOLOCAUST MEMORIAL MUSEUM, COURTESY OF NATURHISTORISCHES MUSEUM, VIENNAthe United States Holocaust MemorialMuseum in Washington, D.C.—shows science’srole in the campaign.The exhibition is slated for a multiyearnational tour. In its Pittsburgh launch,“Deadly Medicine” included several programsheld in collaboration with the Universityof Pittsburgh that delved into the legacyeugenics has left to modern medicine. Pitt’sMargaret McDonald, associate vice chancellorfor health sciences academic affairs, LisaParker, associate professor of human genetics,and David Barnard, professor of medicine,worked with the Warhol to offer a seriesof public talks and forums at the museum.(These were on the heels of a Scaife Hall lectureby Susan Bachrach, curator of the exhibition;her December visit was sponsored bythe C.F. Reynolds Medical History Society.)The Warhol talks featured Pitt medical geneticists,public health experts, physicians, bioethicists,art historians, and even a poet. OnFebruary 20, Arthur S. Levine, senior vicechancellor for the health sciences and dean ofthe medical school, hosted a Dean’s Summitthat drew academic medicine representativesfrom Pennsylvania, Maryland, Georgia, WestVirginia, Ohio, and Washington, D.C. TheSchool of Medicine also offered its studentsa “Deadly Medicine” minielective with a discussionand private exhibition tour led byBachrach and Pitt’s Marta Kolthoff, assistantprofessor of obstetrics, gynecology, and reproductivesciences.The programs were cautionary in nature,reflecting the tone of the exhibition. “DeadlyMedicine” shows how well-respected scientistshelped prosecute mass murder, says Bachrach.“The prevailing image of Nazi medicine isthat they were fanatics and political zealots,that they weren’t mainstream.” That’s not thecase, she says.The exhibition documents the growth ofeugenics from its roots in 19th-century socialDarwinism. In the United States, eugenicsgained popularity at a time when its proponentsclaimed that the “feebleminded” andimmigrants from Southern and Eastern Europeweakened the country’s genetic stock. Writingbooks with Brave New World–like titles, such asSterilization for Human Betterment, eugenicistsin the United States argued to cull the gene poolof those with “less desirable” traits. They evenprevailed upon the country’s highest court.“Three generations of imbeciles are enough,”wrote Supreme Court Justice Oliver WendellHolmes in Buck v. Bell, the 1927 decisionallowing Virginia officials to sterilize CarrieBuck, an unwed mother with an alleged familyhistory of mental retardation. From 1909to 1933, 16,000 people in this country weresterilized, many of them wards of state psychiatricinstitutions. The practice continuedinto the 1970s; by then, 65,000 people hadbeen sterilized.In the wake of a diminishing birthrateafter World War I, Germany stressed fertility.The public health message merged with theracist and nationalist belief that the Nordic“race” was ideal. As the Nazis consolidatedtheir power, a eugenics movement also tookhold. “Deadly Medicine” shows the inexorableslide of German eugenics toward massmurder. The viewer sees still photos of sterilizationoperations before an amphitheaterof German medical students. From 1933 to1945, state doctors sterilized 400,000 disabledand mentally ill Germans, deemed “lifeundeserving of life.”The 1933 Erbgesundheitsgesetz, or lawconcerning hereditary health, paved the way forsuch sterilizations, points out Pitt’s Loren Roth,senior associate vice chancellor, health sciencesand professor of psychiatry and of health servicesadministration. Roth, who participatedin the Dean’s Summit, notes that the field ofpsychiatry was complicit in this campaign. (Healso notes that psychiatrists who objected to thepractice were removed from their positions.)Elimination of those deemed “incurable”would come next. Physicians and midwivesreferred children born with mental or physicaldefects to special pediatric euthanasiaunits, which killed 5,000 children. The exhibitionincludes a stark, metal, white crib, likethose used in the units. It sits empty.Not content with preventing “undesirableoffspring,” the Reich soon targeted the adultdisabled population for extermination. From1939 to 1945, the state killed some 200,000Germans—the most incapacitated of thosehoused in state asylums. To accomplish this,Nazi doctors developed efficient killing strategies,placing victims in gas chambers and burningtheir corpses in crematoria. That set thestage for the “Final Solution” and the annihilationof 6 million. Doctors were there every stepof the way, the exhibition reminds us.“Deadly Medicine” raises enduring questions:How could medicine become such ahand servant of evil? What would each of usdo if confronted with a similar situation?The programs urged participants to considerwhether our society is pursuing questionableideals of biological perfection in itsown way, through plastic surgery, the testingof fetuses, or whatever advances medical sciencehas in store.Pitt School of Law Dean Mary Crossley,whose own scholarship focuses on healthcareinequalities, offered words of caution in herWarhol talk. She worries about an implicitbias against sickness and imperfection.“We really need to be very attentive tothe choices we’re making,” says Crossley,“and [make sure] they promote not only thewelfare of society, but also individual welfareand freedom.”Elimination of those deemed “incurable” would come next.Barnard, a Pitt bioethicist, noted in hisWarhol talk that the Nuremberg Code waslargely responsible for changing the waydoctors conduct human experiments in thiscountry. Among other principles now understoodas dogma, the code states that a studysubject must not only consent to participatein a study, but do so without the risk of coercion,be aware of the scope of the study, andbe able to drop out at any time. It also statesthat the degree of risk scientists take in studies“should never exceed that determined bythe humanitarian importance of the problemto be solved.”Yet, Barnard reminded, some scientists stillpursued highly dubious studies in the States.In 1974, the federal government mandatedthat universities establish institutional reviewboards to oversee human subject research.It’s hard to imagine the Seidens anticipatedwhat awaited them in 1942 as they sat fortheir portraits. The scientists studying themprobably had some idea.“We don’t know what measures about theexpulsion of the Jewish People are plannedin the next months,” wrote one researcher toanother, “which, under certain circumstances,if we wait too long could deprive us of valuablematerial.”■SUMMER 2007 35

ALUMNI NEWSdoorstep for last-minute physicals or cold remedies.He laughs about conducting at least seven basketballphysicals for young athletes in his living room. Throughhis service work in the community—cleaning parksand supporting a drug awareness program—he metan even more recognizable and much-loved denizen ofGreenfield: local pol Bob O’Connor, who would becomePittsburgh’s mayor and his patient. O’Connor died ofcancer last year, less than one year into his first term asmayor. Bernacki says his experience in Pitt’s family practiceresidency prepared him to deal with the psychologicalstates that patients and their families experienceduring illness and at the end of life.CLASS NOTES’50s When Roland Nord started practicingmedicine in New Castle, Pa., he would get a callin the middle of the night if one of his patients endedup in the emergency room. It was his job, as a familyphysician, to go to the ER and care for his patients.That changed long ago with the advent of the ERphysician. But Nord (MD ’55) is still practicing in NewCastle, more than 50 years after graduating from medicalschool. A grateful patient of 38 years noted themilestone in 2005 and alerted the local newspaper,which promptly sent a reporter to Nord’s office. In aletter commemorating Nord’s years of service, ArthurS. Levine, Pitt’s senior vice chancellor for the healthsciences and dean of the School of Medicine, notedthat he appreciated Nord’s words to a reporter for theNew Castle News: “In order to practice medicine well,you not only need to be a scientist, but you need to bea human.”’80s When Leslie Kahl (Internal MedicineResident ’81, Rheumatology Fellow ’83) returned homeafter rounds during her residency, she often stayed uplate into the night reading about rheumatic diseases.She found more questions than answers, making thespecialty intriguing. As a rheumatologist today, shesays she tries to listen closely to what patients sayabout their painful, sometimes debilitating diseases.She served as an assistant professor of medicine at Pittin the 1980s. Now, as a professor of medicine and associatedean for student affairs for the medical school atWashington University in St. Louis, she finds her listeningskills come in handy when she meets with students.While reading a magazine in 1999, critical care specialistMartin Doerfler (MD ’82) learned of a few JohnsHopkins professors who were ICU innovators. The followingyear he joined their fledgling company, VISICU,and is now a vice president for clinical operations there.The company’s eICU solution program combines informationtechnology and staff training to reduce mortalityand mistakes in the ICU.Since completing his residency at UPMC Shadyside,Bernard Bernacki (Family Practice Resident ’84) hastreated patients in the Greenfield neighborhood ofPittsburgh, which is his home. Although he enjoys thewarm response his work receives, it is occasionally toofamiliar. Patients and neighbors might show up on hisMARTIN SPRINGERPUMP UP THE GAMOW BAG’90s When the radio crackled and theoperator said that there was a car over the mountainside,David Sherwood (MD ’90), a family practicephysician in rural Colorado, knew that the driver probablyneeded treatment as soon as possible. Sherwoodarrived first at the scene of the accident. He saw anoverturned car about 500 feet down the mountainside,so he grabbed his jump kit and roped down.After reaching the car and finding it unoccupied, hebegan to search the nearby brush, eventually findinga woman, splayed on a rock, unresponsive. Shehad been lying there 12 hours. Sherwood stabilizedher before the mountain rescue team arrived witha helicopter to transport her to the nearest traumacenter, about 110 miles away. (She later recovered.)Sherwood is one of three doctors for a clinic—whichhe owns—that treats about 3,000 people in the SanJuan Mountains of Colorado. Serious car accidents likethis occur about every other month, says Sherwood,medical director of Ouray County Search and Rescue.His clinic is about 30 miles from the nearest hospital.If a patient can’t pay, Sherwood has been known toMartin Springer (MD ’82) wants all his classmates to know: If you are ever inChina, you really ought to look him up.Rather than settling down and starting a family, Springer long ago optedfor packing his bags and starting a family.At the University of Chicago, he completed the emergency medicine residency hebegan at Pitt. He later worked at the Chicago Medical School’s teaching hospital onthe boundary of competing gangs. “We saw a lot of trauma,” he writes of the six yearshe was in Chicago, “some of it inflicted in the ER waiting room.”During those years, Springer took two four-month breaks to work in Nepal, caringfor locals and tourists. At the clinic near Mount Everest, he and his colleagues introducedthe Gamow Bag, a portable, hyperbaric chamber used to treat altitude sickness.Filled with air by a pump used to inflate a raft, it looks like an inflated duffle bag bigenough to hold a person, and it’s now standard issue on high-altitude expeditions.A few years later, Springer relocated to Kathmandu with his wife and son and joinedthe staff of the CIWEC Clinic Travel Medicine Center, which cares for tourists, expatriates,and members of the diplomatic community. There he saw infectious diseases from36 PITTMED

Dentistry—wrote theaccompanying editorial.Legro is a professor ofobstetrics and gynecologyat Pennsylvania StateUniversity in Hershey, Pa.Levi Downs (MD’94), assistant professorof obstetrics, gynecology,and women’s healthat the University ofSherwood grabs his jump kit and disappears down the mountain. Minnesota, is glad thereis now a vaccine to preventwomen from contracting human papilloma-accept elk steaks or other services as payment.Anita Courcoulas (General Surgery Intern ’89, virus (HPV), which causes most cervical cancers.Surgery Resident ’95, Pediatric Surgery Fellow ’96, But he notes the vaccine won’t help womenMinimally Invasive Surgery Fellow ’00) leads Pitt’s who already have the virus and are susceptibleDivision of Minimally Invasive Bariatric and General to cervical cancer. He is investigating ways toSurgery. Courcoulas studies the outcomes of bariatric shut down the proteins in HPV that cause thesurgery through several National Institutes of Health growth of new blood vessels that feed tumors.grants. Because of several common side effects— He experiments with RNA interference to stopincluding nausea, dehydration, mood change, hair loss, the mechanism.and excess skin—she says it’s important that researcherscontinue to delve into these areas. She serves as professor of surgery at Washington UniversityDoug Schuerer (MD ’95), an assistantprincipal investigator on a longitudinal study of bariatricsurgery in children. The methodology paper on the problems that trauma surgeons see there, suchin St. Louis, researches a number of commonstudy came out in April.as ATV and hunting accidents and blood infections.He has been named medical director ofDuring his residency at Magee-Womens Hospitalof UPMC, Richard Legro was inspired by David Guzick, trauma at Barnes–Jewish Hospital and says heMagee’s director of the Division of Reproductive enjoys trauma surgery because it allows himEndocrinology at the time, who shared his loveto operate on the whole body. In January, heof medical research. When Legro (Obstetrics and advocated for a Missouri bill proposing fines forGynecology Resident ’91) published a paper in The drivers who don’t wear seat belts. He and hisNew England Journal of Medicine this year examining wife, Nickie Kolovos (MD ’96)—spotlighted inthe common treatments for polycystic ovary syndrome our Fall 2006 “The Way We Are”— expect their(PCOS), he was pleased to see that Guzick—now dean first child in July.of the University of Rochester School of Medicine and—Meghan Holohan & Chuck Staresinicall over the world, including typhoid, trypanosomiasis,schistosomiasis, malaria, dengue fever, visceral leishmaniasis,and Japanese encephalitis, to name a slew.Playtime was also an adventure.“I was lucky enough to be able to visit many of theA Brahman offers blessings toSpringer (in blue) before the doctor remote parts of Nepal, kayak its rivers, and spend timekayaks down the Kali River along the with well-known members of the climbing and adventuringcommunity,” he writes.western border of Nepal.Today, Springer is chair of the emergency departmentin a rapidly growing private-venture hospital in Beijing. His outdoor pursuits nowtake him to remote Mongolia, where, “Instead of Nepali tea and coconut biscuit, it isalcoholic fermented mare’s milk and dried, rock-hard cheese.”Where will Springer be in a few years’ time? Good question. He is looking forwardto the 2008 Summer Olympics in Beijing. But his son plans to begin college this yearin Colorado. Better note Springer’s location in pencil, not ink.—Chuck Staresinic & Katie HammerTHE WAY WE ARECLASS OF ’97Sherri-Ann Burnett Bowie (MD ’97) isan instructor of medicine in Harvard MedicalSchool. During her work on her MPH atHarvard, which she earned in 2005, Burnett Bowienoticed that often people with vitamin D deficienciescouldn’t process insulin as well as other people. Soshe is pursuing a study that will explore the connectionbetween the two disorders. In 2005, she won theMassachusetts General Hospital Physician-ScientistAward and in 2006 she was a Chester Pierce ResearchSociety Speaker at the hospital. Burnett Bowie says theproblem-based learning sessions in medical school weregreat preparation for her work in endocrinology.Pitt also prepared Devin Brown (MD ’97) forher career at the University of Michigan as a physicianscientist.As medical students, Brown and classmateTeresa Smith (née Jacobs, MD ’97) investigatedthe prevalence of primitive reflexes in healthy youngadults to aid clinical evaluations of neurological disease.These infantile reflexes do not typically persistinto adulthood, unlike, say, the sneeze reflex. Butthey are common in patients with frontal lobe lesions,schizophrenia, and Alzheimer’s disease. In 1998, theduo published their paper in Neurology with the helpof former Pitt neurologist Laurie Knepper (MD ’85).Today as an assistant professor of neurology, Brownstudies sleep apnea in stroke patients.As the training director of the Office of CriticalEvent Preparedness and Response and assistant professorof emergency medicine at Johns HopkinsUniversity, Ed Hsu (MD ’97) travels throughout theworld evaluating medicine and public health problemsin disaster-prone areas.Hsu has worked with physicians and healthcareprofessionals in many nations, training doctors tohandle medical situations following emergencies.One month after classmate Brian Klatt (MD’97) completed his tour as an attending orthopaedicsurgeon in the U.S. Air Force, he visited Nepal andmet some of Hsu’s colleagues who were helping theNepalese plan for emergency care during earthquakes.Klatt served for five months in a field hospital at CampAnaconda in Balad, Iraq, north of Baghdad, wherehe stabilized U.S. soldiers for transport to Germanyand performed surgeries for Iraqis. During that time,though there were only three orthopaedists at thecamp, more than half of the 1,200 surgeries the doctorsperformed were orthopaedic.Klatt now works as a fellow in adult reconstructionat Thomas Jefferson University in Philadelphia. Whenwe spoke with him, he was organizing his class’s eventsfor Medical Alumni Weekend. —MHSUMMER 2007 37

ROBERT BASFORDAUG. 21, 1923–MAR. 11, 2007Robert Basford enjoyed life as a scientist so muchthat it would surprise many who knew him tolearn that his formal education nearly came toan end after high school. The North Dakota native toldhis students that he danced in the street for coins duringthe Great Depression. As a young man, he was an officemanager before starting college. He received his PhDBasfordfrom the University of Washington in 1951 and spentfive years on fellowships at the University of Wisconsin, Madison.His career at the University of Pittsburgh School of Medicinebegan in 1958, when he joined what was then the Department ofBiochemistry. Students and fellows remember him as a hands-onscientist who never hesitated to do the hard work himself or to givecredit where credit was due. He was an avid cook and gardener who,with his wife, Carol Phebus-Basford (MD ’68), once invited his labgroup over to see his night-blooming cactus. He made importantcontributions to understanding metabolism in the immune systemand in the brain. He was acting chair of his department for four years,beginning in 1976, and retired as an emeritus professor in 1993.—Chuck StaresinicANDREW KEVERLINEAPR. 13, 1974–JAN. 22, 2007Around his hometown of Warren, Pa., AndrewKeverline was admired as the charismatic doctorwho returned from the city to take over his dad’sophthalmic practice following the elder Keverline’s death inKeverline 2002. Then Andrew Keverline (MD ’00, Res ’04) died thiswinter in a snowmobile accident in northwestern Pennsylvania.He was 32 years old.Keverline was the fourth in his family to graduate from Pitt’sSchool of Medicine. He followed his father, Paul Keverline (MD’69), brother Michael Keverline (MD ’97, Res ’01), and sister-in-lawSharon Keverline (MD ’97, Res ’01).’40sALFRED R. CONTIMD ’44MAR. 10, 2007ROBERT E.JOHNSTONMD ’46DEC. 31, 2;006IN MEMORIAM’50sJAMES C. FRIESMD ’50JAN. 16, 2007RICHARD W.ZIMMERMANRES ’57JAN. 30, 2007KENNETH KOSTMD ’59MAR. 28, 2007’60sHOWARD B. EISENMD ’60MAR. 12, 2007ROBERT H.BROUGHERMD ’61NOV. 21, 2006ROY E. BOHLMD ’62OCT. 2, 2006BERNARD I. COHENMD ’64JAN. 26, 2007“Andy’s dream was always to go back and practice with ourdad,” said Michael Keverline. Their father died one year beforethat could happen.“He could have gone anywhere after residency. But he wentback [to Warren] nine months after Dad died. Andy was fiercelyloyal, and he had a strong sense of responsibility.”Keverline is survived by his wife and two children, ages 3 and 4.—CSJAMES A. MAGOVERNJUNE 8, 1954–MAR. 17, 2007When James Magovern (MD ’80) was diagnosedwith renal cancer in 2003, he put hissurgical practice on hold to devote time tohis research and his family. Magovern was the principal Magoverninvestigator on a National Institutes of Health study ofa left ventricular device. He was also director of cardiac surgeryresearch at Allegheny General Hospital and surgical director of thehospital’s Gerald R. McGinnis Cardiovascular Institute. Two of hisresearch papers were in press at the time of his death. The fatherof four hails from an esteemed medical family. His father, GeorgeMagovern, was an early leader in developing artificial heart valves.Brother George Jr. received his MD from Pitt in 1978. DaughterMegan is currently in medical school. —CSCAMPBELL MOSESFEB. 12, 1917–FEB. 11, 2007Aplanned birthday party for Campbell Moses(MD ’41) suddenly became a memorial service,but it remained a celebration of his life. Mosesdied February 11, one day before his 90th birthday.Moses earned his undergraduate and medicaldegrees at the University of Pittsburgh. He was aresearcher who took part in the clinical trials of Jonas Moses, c. 1958Salk’s polio vaccine and an associate professor ofphysiology and pharmacology. He directed and helped build theAddison H. Gibson Laboratory, which re-established live animalresearch at Pitt.Moses left Pittsburgh for New York City in 1967 and becamethe medical director of the American Heart Association. Peerscalled Moses a gifted communicator and innovative medicaleducator who used film as an educational tool as early as 1949.After leaving the association in 1973, he was senior vice presidentfor medical services at Medicus, a medical communicationsagency. He was an enthusiastic Manhattanite, frequently walkinghis adopted city and reveling in the many restaurants, cafes, andneighborhood shops where he was known by name.Among the fond memorial service remembrances from his fourchildren was a thank-you for demonstrating how to live a “principledand ethical life” and for “trying hard” to teach a son how totie a bow tie. One of his 12 grandchildren added, “I am gratefulyou weren’t afraid to roll around on the floor and be silly. Thankyou for keeping tetanus shots in your freezer.” —CS38 PITTMED

MICHAEL GREVERON SECOND CHANCESBY CHUCK STARESINICLINDA WALLENMichael Grever (MD ’71, Res ’74)has learned that believing in secondchances can pay off. An experimentaldrug he championed that once seemedineffective now shows promise for leukemiapatients.Grever, who also received his undergraduatechemistry degree from Pitt and was recognizedrecently as one of the University’sLegacy Laureates, was a full professor in theDepartment of Internal Medicine at OhioState University in the 1980s. There, he ransome of the first clinical trials of new cancerdrugs. He would receive drugs from theNational Institutes of Health (NIH) withinstructions. His job was to determine theirefficacy and to evaluate, when something wentwrong, whether it was because of the newtherapy or the underlying disease. Later, at theNational Cancer Institute (NCI), he learnedhow the instructions were written. In 1989,Grever became deputy director of the NCI’sDivision of Cancer Treatment and Diagnosis.Grever eventually directed the institute’sdrug discovery and drug development programsfor cancer and AIDS. His team crackedopen the molecular biology of exotic newcompounds in search of targeted cancer therapies.They brought the most promising onesforward through animal studies until they wereready for clinical trials.“As a result, we put about 19 to 21 newMEDICAL ALUMNI ASSOCIATION OFFICERSMARGARET LARKINS-PETTIGREW (MD ’94)PresidentJOHN F. DELANEY (MD ’64)President-electGRAHAM JOHNSTONE (MD ’70)SecretaryPETER FERSON (MD ’73)TreasurerROBERT E. LEE (MD ’56)HistorianAn experimental leukemia drug Grever championed actually kills cancer too fast.DALE ADAIR (MD ’85)PATRICIA CANFIELD (MD ’89)JOHN KOKALES (MD ’73)DONALD MRVOS (MD ’55)BRETT PERRICELLI (MD ’02)DAVID STEED (MD ’73)Members at LargeSUSAN DUNMIRE (MD ’85)Executive Directortherapies into patients with cancer or AIDS,”he says, including pentostatin and fludarabine.In the early 1990s, Grever and colleagues atthe NCI began looking at a drug called flavopiridolas a treatment for chronic lymphocyticleukemia (CLL). In the Petri dish, it was a winner.There was a lot of excitement about movingit into Phase I testing in humans. Whenthey tried it in patients, however, it bombed.“It didn’t do anything,” says Grever. “Itjust produced diarrhea, and that wasn’t a veryattractive side effect.” These disappointingresults were repeated across the United Statesand in Europe. Before long, the drug companydecided to drop the project, and the NIHbegan to lose interest, too. But Grever wantedan explanation.In the lab, his team took human leukemiacells suspended in the patient’s own plasmaand figured out how much drug was needed tokill the cancer cells. It took a much higher concentrationof drug than anyone had thought itwould. Why? The original lab tests used fetalcalf serum, because human plasma is prohibitivelyexpensive. Most of the drug was boundto human plasma protein and unavailable forkilling cancer—something that hardly happenedat all in calf serum.Grever personally lobbied the NIH and thedrug company to test flavopiridol again withdifferent dosages and a new schedule of drugadministration. These studies were conductedin his research laboratory at Johns HopkinsUniversity. Shortly therafter, he was back atOhio State as chair of internal medicine—aposition where he could make the drug a priority.In clinical trials, Grever says, the drug “wasso effective that, for a while, it was killing theleukemic cells too fast. We went to the FDA,and they said, ‘Well, you can’t give up on this,because it’s very promising.’”In fact, the rapid destruction of a largenumber of cancer cells can cause a majorproblem, because the body must clean up themess and the toxic byproducts. Grever hopesflavopiridol can be used in combination withother proven leukemia drugs to achieve completeremission. He and colleagues reportedthe latest news on flavopiridol this January inthe journal Blood, but there will soon be more.They have a Phase II study in CLL patientsunder way, and other institutions are trying toreproduce their work.“We’ve treated over 80 patients,” Greversays, “and this is all holding up. This is goingto be one of the most active agents in the treatmentof this disease.”■M-200k Scaife HallUniversity of PittsburghPittsburgh, PA 15261tel 412-648-9090; fax 412-648-9500medalum@medschool.pitt.edu SUMMER 2007 39

LAST CALLFRANKENSTEIN’S BIRTHDAYIt was a dark and stormy summer at Lord Byron’s Lake Geneva home.Seeking a playful literary distraction for his guests—the soon-tobe-wedMary and Percy Shelley as well as his physician, John Polidori—Byronchallenged them each to pen a horror story to share. Thefollowing spring, in May 1817, Mary Shelley finished Frankenstein; or,The Modern Prometheus, which many consider the first science fictionnovel. It was published anonymously the next year. (For his horrorstory challenge, Byron himself wrote a bit about the vampire legendshe had heard in his travels, inspiring Polidori to later write The Vampyre,the first book in the romantic vampire genre.)Shelley had a vivid imagination, but medical science also contributedto her story. A National Library of Medicine exhibition reports:Scientists and physicians of her time, tantalized by the elusiveboundary between life and death, probed it through experiments withlower organisms, human anatomical studies, attempts to resuscitatedrowning victims, and experiments using electricity to restore life tothe recently dead.PHOTO COURTESY THE BAKKEN LIBRARY, MINNEAPOLIS40 PITTMED

C A L E N D A ROF SPECIAL INTEREST TO ALUMNI AND FRIENDSFor information on an event,unless otherwise noted, contactthe Medical Alumni Association:1-877-MED-ALUM, 412-648-9090, ormedalum@medschool.pitt.edu.MEDICAL ALUMNIWEEKEND 2007MAY 18–20Reunion Classes:1947 19521957 19621967 19721977 19821987 19921997SENIOR CLASS LUNCHEONMAY 1811 a.m.Soldiers & Sailors Memorial HallPITT MED REUNIONLEMONADE SOCIALMAY 181:15 p.m.Schenley Park Visitor CenterRSVP to:Victoria Shaversvictoria@pmhsf.org412-802-8319SCHOLARSHIPAPPRECIATION TEAMAY 183:30 p.m.William Pitt Union Lower LoungeALUMNI WEEKENDOPENING RECEPTIONMAY 185:30 p.m.Holiday Inn Select University CenterCLASSES OF 1957 & 1972DINNERSMAY 187 p.m.Pittsburgh Athletic AssociationSCOPE AND SCALPEL’S“DESPERATE HOUSESTAFF”MAY 18 & 197:30 p.m.The Antonian TheatreCarlow UniversityFor information:www.scopeandscalpel.orgCME LECTUREMAY 198:30 a.m.M. Michael Barmada, PhD, Speaker“Genomic Medicine: From theHuman Genome Project toPersonalized Medicine”Scaife HallALUMNI BRUNCH &MEDICAL SCHOOL TOURMAY 1910 a.m.Scaife HallREUNION GALAMAY 196 p.m.Senator John Heinz History CenterSENIOR CLASS PICNICMAY 20NoonCathedral of Learning LawnCLASS OF 2007COMMENCEMENTMAY 2110 a.m.Sherwin Nuland, MD, SpeakerCarnegie Music HallSIMMONS LECTUREMAY 238 a.m.John C. Alverdy, MD, SpeakerRoom S100Starzl Biomedical Science TowerFor information:www.surgery@upmc.eduTO FIND OUT WHAT ELSE IS HAPPENING AT THE MEDICAL SCHOOL, GO TO www.health.pitt.edu

YOU COULD WATCHTHE GRASS GROWBut it might be time to take action to grow your legacy atthe School of Medicine. Your support is needed. Help sowthe seeds of success for future generations of medical students.In addition to contributing to your alma mater, youcould establish a gift that would provide you (and/or aloved one) with an annual stream of income for life as wellas tax advantages. There are many giving opportunitiesthat could benefit both the school and you.For information, please contact: Kathleen Helling,Director of Planned Giving, at 412-647-4220 or athkathleen@pmhsf.org.PHOTO COURTESY J. MIKSCH. ASSOCIATE EDITOR JOE MIKSCH’S GRANDMOTHER AND GRAND-FATHER MARGARET AND HENRY MIKSCH (RIGHT) WITH FRIENDS. PHOTO CIRCA 1940.UNIVERSITY OF PITTSBURGHSCHOOL OF MEDICINESUITE 401 SCAIFE HALLPITTSBURGH, PA 15261CHANGE SERVICE REQUESTEDNONPROFIT ORG.U.S. POSTAGEPAIDPITTSBURGH, PAPERMIT NO. 205