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PITTMEDUNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE MAGAZINE, FALL 2006 (AUG/SEPT/OCT)VOL. 8, ISSUE 3DEPARTMENTSOF NOTE 3Why are some generations moreviolent than others?Can aspirin kill cancer?CLOSER 7Skulldiggery.INVESTIGATIONS 8Omega-3s and the other white meat.A student probes how environmentaland genetic factors relate in Parkinson’s.In the future, we may cure “senior moments.”ATTENDING 32The graduating class president on losingand finding yourself in med school.Katrina Firlik on memorable stains.MATCH RESULTS 35And they’re off ...ALUMNI NEWS 36Toxic avenger.Doctoring in rural America.LAST CALL 40The Starzl trainee migration.FEATURESNext of Kin 12In the world of organ donation, tens of thousands of secondchances begin with a tragic loss. Families of deceased organ donorslet us into their lives.PHOTO-ESSAY | PHOTOGRAPHY BY CHARLEE BRODSKYTEXT BY ELAINE VITONE12CONTRIBUTORSWhen CATHERINE LAZURE [Cover, “Make Like a Salamander”] finishes a piece, out comesthe tape. Sticky side down, she dabs at cloth and stitching, hoping to rid the creation of felinedetritus. Having three cats can complicate matters for an illustrator who works with fabric.To find the right velour or paisley for her appliqué technique, Lazure frequents thrift storesand cannibalizes her wardrobe. Her artistic influences include Joan Miró and Paul Klee. TheNew Yorker and The New York Times are among Lazure’s clients. Lazure also is the illustrator andcoauthor of Agathe, la Diva de Zambalou (2000, Les 3 Orangers), a children’s book about a singinggiraffe. The Montreal native lives and works in West Harlem.Simultaneously riveting and tranquil, the photographs of CHARLEE BRODSKY [ “Next ofKin”] are inherently sympathetic. Brodsky, a professor of photography in the design departmentof Carnegie Mellon University, concentrates her work largely on social and community issues.Although she does not take assignments often, Brodsky made a second exception for Pitt Med(the first came in our August 2004 issue with “Ghost Body”). She considers herself a documentaristand says that she tries to enter her subjects’ lives as gently as possible in an effort to understandtheir stories. Currently, Brodsky is pursuing a project that focuses on the distress involvedwith mental illness.COVERRSalamanders and newts do it, so why not us? With funding from the Department of Defense, a multidisciplinaryteam will attempt to grow back mammalian digits. (Cover: Catherine Lazure © 2006)Break on Through 18Our Thomas Starzl story continues with talk of tolerance and snailfur. Starzl Institute leaders ponder these topics in their attemptsto do away with the need for immunosuppressive drugs.BY CHUCK STARESINICMake Like a Salamander 23Can a salamander teach us how to grow back limbs?COVER STORY BY JOE MIKSCHDifficult Gifts 28What a rare and harrowing disease can reveal.BY ERICA LLOYD

DEAN’S MESSAGEPITTMEDPUBLISHERArthur S. Levine, MDEDITOR IN CHIEFErica LloydART DIRECTORElena Gialamas CerriSENIOR EDITORChuck StaresinicASSOCIATE EDITORJoe MikschPRODUCTION COORDINATORChuck DinsmoreSTAFF CONTRIBUTORSAlicia Kopar, Jaclyn MaddenOBITUARIES CONTRIBUTORMacy Levine, MD ’43CIRCULATION MANAGERCrystal KubicCHIEF EDITORIAL ADVISORKenneth S. McCarty Jr., MD, PhDEDITORIAL ADVISORSEdward Barksdale Jr., MDSteve N. Caritis, MD, Res ’73Paula 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, MDGabriel Silverman, Class of ’09Peter Strick, PhDGerard Vockley, MD, PhDSimon Watkins, PhDMarshall Webster, MD, Res ’70Julius Youngner, PhDOFFICE OF PUBLIC AFFAIRSRobert HillJohn D. Harvith, JDSome people, says Bloom, can see themote in others’ eyes but they can’t seethe beam in their own.—James Joyce, UlyssesIn the “Cyclops” chapter, modeled afterHomer’s tale, Joyce’s Bloom narrowly escapes from“the citizen,” a blowhard nationalist he meetsin a tavern. Although Bloom’s nemesis has botheyes, he can’t see more than one viewpoint. Here’sanother cyclops story—in this one, the characterscan recognize complexity and keep their eyes wide open.I was pleased to host recently Dr. Philip Beachy as one of our Laureate Lecture seriesspeakers. Dr. Beachy is a professor of molecular biology at Johns Hopkins University, aHoward Hughes investigator, and a member of the National Academy of Sciences. He isknown for revealing how the secreted proteins of the Hedgehog gene family mediate theproliferation and differentiation of embryonic cells. The peculiar Hedgehog name comesfrom Christiane Nüsslein-Volhard and Eric Wieschaus, who won the Nobel Prize for theirclassic mutant screens. In 1977, they identified a mutation in the fruit fly affecting its outerbody layer. These scientists observed that the mutant fly embryo, with small spiky projectionsinstead of orderly segments, resembles a hedgehog. Beachy cloned the fly’s Hedgehoggene; he and others then went on to show that the gene is highly conserved in evolution andthat the best-studied one, Sonic hedgehog (named for the video game character), regulatesthe organization of the midline structures of the brain in vertebrates. Mice with a disruptedSonic gene are cyclopic. Mutations in the human version of the gene cause holoprosencephaly,a defect in which the embryonic forebrain doesn’t divide into hemispheres and whichcan result in cyclopia. Dr. Beachy found that too much Hedgehog activity is equally bad: It’sresponsible for some cases of basal cell carcinoma (the most common human cancer) and thechildhood brain tumor, medulloblastoma—both driven by excessive proliferation of precursorstem cells.The plot thickens: In the 1960s, it was noted that sheep who graze on corn lily give birthto cyclopic lambs; the plant contains cyclopamine, a teratogen. Dr. Beachy found that thismolecule blocks the Hedgehog signal and inhibits the growth of medulloblastoma as wellas human prostate cancer cells transplanted in mice. (In fact, the level of Hedgehog geneactivity may be helpful for prostate cancer prognosis: Metastatic prostate cancer cells haveincreased expression of the Hedgehog gene, and nonmetastatic cells do not.)Several companies are now developing cyclopamine-like drugs as potential cancer therapies,and others are developing drugs that might augment Hedgehog expression. Given thatDown syndrome patients have too few brain cells, it could be that treating a Down fetus inutero with such a drug might reverse some of the defects found in this syndrome. Such adrug might even help with myocardial ischemia. In any case, the moral of this story: Startingwith an observation 30 years ago by the keenest of basic science eyes, a fruit-fly mutationnow promises to illuminate the most fundamental mechanisms critical both to normalhuman development and to cancer, leading to possible remedies as well. What more couldone ask of basic science, and what better definition of “translational research”?JULIA MAROUS STRAUTPitt Med is published by the Office of the Dean and Senior ViceChancellor for the Health Sciences in cooperation with the alumni andpublic affairs offices. It is produced quarterly for alumni, students,staff, faculty, and friends of the School of Medicine. PR 5645The University of Pittsburgh is an affirmative action, equalopportunity institution. © 2006, University of PittsburghArthur S. Levine, MDSenior Vice Chancellor for the Health SciencesDean, School of Medicine2 PITTMED

OF NOTEDevoted to noteworthyhappenings at the medicalschool ... To stay abreast ofschool news day by day, seewww.health.pitt.edu.BiosensibleOne’s got the imaging equipment and know-how. The other has some of themost advanced fluorescent dyes available.Together, the University of Pittsburgh and Carnegie Mellon University will beable to delve more deeply into how cells work and make the body function.With a $13.3 million grant from the National Institutes of Health, Pitt andCMU are creating a National Technology Center for Networks and Pathwaysthat’s housed at CMU’s Mellon Institute. In the words of Simon Watkins, directorof Pitt’s Center for Biologic Imaging, the technology center will “help developand build new ways of studying the molecular pathways that exist inside a cell.”The grant will allow Alan Waggoner—director of CMU’s Molecular Biosensorand Imaging Center, who is known in scientific circles as the king of fluorescentdyes—and Watkins—widely acknowledged as a guru of biologic imaging—to Pitt and CMU partner to probe cells in new ways.combine their complementary skills to probe and observe cells in novel ways.Already, Watkins says, they have plans to obtain the first handheldconfocal probe, a device with an imaging tip the size ofa pencil eraser. “It allows us to probe things you can’tget an ordinary microscope into.” —Joe MikschFOOTNOTECOURTESY S. WATKINSAs Pitt students explore the Wyoming“Dinosaur Graveyard,” which rancher Allen Cookdeeded to the University this year, they needn’t lookfor a T-Rex old folks home.Adolescents experience bouts of angst. A zit!?!?! Onprom night!?! But usually they mature into well-adjustedadults. More than Sturm und Drang was in store fordinosaurs at puberty, though. In many cases, researcherssay, sexual maturity led to the end of life. Child-rearingstresses for females and fights between males overmates meant few saw the far side of 16.KILLING CANCER WITH ASPIRINYong Lee believes he has found a novel and cheap way to curtail aggressiverecurring cancer: aspirin.Lee is a PhD professor of surgery and pharmacology at the University ofPittsburgh. He’s found that cancer cells in culture resistant to a new treatmentcalled TRAIL respond to the treatment after being dosed with aspirin for at least12 hours. TRAIL is designed to induce programmed cell death. Aspirin, Lee says,blocks signaling pathways that cancer cells need to survive and allows TRAIL todo its job on cells that would otherwise have developed resistance to it from afirst round of therapy.Lee says his lab will soon experiment with animal models and is working ondeveloping aspirin/TRAIL human protocols. He can’t predict when the therapymight become available in the clinic but notes that TRAIL is in clinical trials andaspirin already has FDA approval, which could expedite the process. —JMFALL 2006 3

Faculty SnapshotsA&Qwith Anthony Fabio on Violent GenerationsOne line from Hannah Arendt’s On Revolution sticks with Anthony Fabio (shown above), aUniversity of Pittsburgh assistant professor of neurological surgery. His recollection of itis written on a dry-erase board in his office in Pitt’s Center for Injury Research and Control:“The hope of man in his singularity is in the fact that not man but men inhabit the Earth andform the world between them.” As an epidemiologist, Fabio wonders about society’s influenceon young people, particularly in relation to shifts in rates of violence. Following his curiosity,he teamed up with Distinguished Professor of Psychiatry Rolf Loeber, principal investigatorfor a longitudinal study of inner-city boys known as the Pittsburgh Youth Study, to look at theissue from a generational perspective.What they asked and found:We focused on two generations. … The oldest generation, even at the same age, reports moreviolence than the younger generation. And so then our question was: Why? [Our] results suggestto us that the difference in reported violence isn’t due to the generations being different,i.e., they are not worse kids, but that some macrolevel effects—period effects, such as theeconomy or changes in cultural norms—are the reason behind the differences in the generations.So if we could magically switch the generations between the time they grew up we wouldsee the [younger] generation now report more violence because they are now the ones exposedto this period effect.How this approach stands out:In the early ’90s we saw a decrease in violence. [Freakonomics authors Steven Levitt andStephen Dubner] estimated that up to 50 percent of the decrease had to do with the legalizationof abortion. [They reasoned that] there were fewer unwanted children. My results reallydon’t support that at all.Many [other studies about the causes of violence are looking at] things like the unemploymentrate, and the census data, and the rate of violence in a specific area. It’s important tomove beyond that. … If we can find out what this period effect is, we could [try to] find theright data ... to predict future epidemics of violence.His questions for us:Is there anything you can do as an individual to affect societal forces? Is there anything youcan do as an individual in response to societal forces? —Interview by Elaine VitoneCAMI MESAMerrill Egorin has won the American Associationfor Cancer Research’s (AACR) Joseph H.Burchenal Clinical Research Award. The awardrecognizes Egorin’s contributions to making chemotherapysafe and effective.Egorin, professor of medicine and pharmacology inthe University of Pittsburgh School of Medicine, beganhis life as a cancer researcher in 1968; he has been atPitt since 1998. The MD has developed rules forusing chemotherapy drugs based on theirpharmacologic features, toxicity profiles,and effects on body function.His efforts, the AACR says, enableddoctors to administer drugs whose toxicityallows for little error in terms of dosing.EgorinPitt’s Bernard Fisher was honored at the samemeeting this year with the AACR’s Award for LifetimeAchievement in Cancer Research. Fisher, who earned hisMD from Pitt in 1943, did early groundbreakingwork in breast cancer metastasis,led clinical trials that foundlumpectomy to be just as effective astotal mastectomy, and established theeffectiveness of the synthetic estrogentamoxifen in treating breast cancerFisherand as a preventative measure against thedisease. The Distinguished Service Professor of Surgeryreceived the Burchenal award in 1998.For 60 years, the American Cancer Society(ACS) has supported research at Pitt.Robert Sobol is the latest Pitt researcherto be awarded an ACS grant.Sobol, a PhD assistant professor of pharmacology,recently received $720,000 from the ACS toSobolpursue research into temozolomide (TMZ), a novel chemotherapeuticagent being used to treat glioblastoma,considered an essentially incurable form of brain cancer.Sobol seeks to understand the molecular basis for resistanceto TMZ in some brain cancers. The grant runs untilJuly 2009.Pitt has 10 other active ACS grants totaling about$6 million. Christopher Widnell, ACS scientific programdirector for extramural grants (and a professor emeritusin the medical school), says that figure puts Pitt at numbersix nationally in terms of ACS funding.Sobol sees an ACS grant as an important step for ajunior investigator: “I’m extremely pleased with the helpof the ACS in getting my research lab on solid footing.”Pitt and ACS will celebrate their long-standing relationshipin a September award ceremony. —JM4 PITTMED

Young Scientist,Get a LifeJULIETTE BORDAIt’s a life that has been in sync with the academic calendar since kindergarten.Imagine you’re a scientist who has finally worked your way intoa junior faculty position. With the right combination of luck, work (lots ofwork), and ingenuity, you’ll get tenure, your own lab, and make a significantcontribution to your field.But, silly you, you also got married, have two young children, like togo out to a movie once in a while, and have a hankering to, on occasion,read something that’s not a scientific journal. Well ...Well, reportedly, it can be done. Melissa McNeil, who has an MD andMPH, is chief of women’s health and associate chief of general medicineat the University of Pittsburgh. She was among those giving adviceduring a panel discussion titled “Striving for Sanity” that was part ofa three-day course in scientific management and leadership for younginvestigators. To the budding scientist looking to make a mark and havea life, McNeil offered these and other tips:• Schedule fun time and stick to it. You schedule your workday andnever shirk obligations. Do the same with your free time.• Learn to say “no.” If at all possible, find a mentor who will help youdecide what’s worth going the extra mile for and what you should pass up.With support from the Burroughs Wellcome Fund and Howard HughesMedical Institute Partners in Scientific Training Program, the Office ofAcademic Career Development offered the sessions designed to help attendeeson the path through academia. The program touched on such topics ashow to navigate the politics of the academy and apply for grants. —JMPITT/UPMC TO RUN SICILIANSCIENCE CENTERLast year, an 11-year-old Sicilian boy affected by severe respiratoryfailure was the recipient of the first pediatric double-lung transplantin southern Italy. The Mediterranean Institute for Transplantation andSpecialized Therapies (ISMETT), which UPMC cofounded seven yearsago, has been home to other medical firsts in the region. In light ofISMETT’s successes, the University of Pittsburgh and UPMC have beenasked by the Italian president, the president of the region of Sicily, andItaly’s National Research Council to run a major new research center inSicily. The $400 million Biomedical Research and Biotechnology Center(BRBC) will house programs that build on Pittsburgh’s strengths in computationaland structural biology, vaccine development, drug discovery,molecular imaging, tissue engineering/regenerative medicine, andneuroscience. Italy will construct the 400,000-square-foot center in theprovince of Palermo. The facility will open its doors perhaps by 2010,though collaborations may begin as soon as this year.Organizers say no other center in Italy has the critical mass ofscientists and research projects proposed for BRBC. They envision thecenter strengthening Italy’s scientific position in relation to other industrializednations and spurring biotechnology research and commercialactivity in Italy and Pittsburgh. —Erica LloydFor more information on potential BRBC collaborations:Arthur S. Levine at levine@hs.pitt.eduMedical Journalism 101At 2:30 one afternoon, the Falk Library of the Health Sciences’ computer labhas become a newsroom. Six University of Pittsburgh med students typeurgently. Deadline is in half an hour, and they need 500 words on a Britishstudy of how breast asymmetry may be a risk factor for breast cancer.Each of those 500 words has to be comprehensible to a layperson. Thefirst rule of the School of Medicine’s minicourse Medical Journalism 101:Know your audience. The professor, KDKA’s medical correspondent MariaSimbra (MD ’93), reminds her students to imagine they are writing to a“really smart 5th-grade science student.” They’re getting used to it.Homework for the third meeting of this four-session, ungraded courseasked them to explain an organ, medical device, or drug. Gaurav Shukla,a second year MD/PhD student, wrote about the chemical processessmokers undergo. Using analogies, Simbra says, helps readers comprehendscientific concepts. So Shukla compared the adrenaline rush smokersget to the feeling of “being late for a big meeting.”MD/PhD student Aaron Secrest, who studies epidemiology, says thathe entered the course because of the inadequacies he sees in medicaljournalism. “A lot of it oversteps its bounds or is just wrong,” he says. Butthe course is giving him a new view of the field: “Journalism, in general,is very difficult.”As students devise a KDKA broadcast plan for the breast cancer study,Simbra advises Secrest that they probably can’t use a graphic displayinghow to measure cup size.“I don’t know what you can and can’t do with TV,” he says. “If it wasFox, you could probably do more.” —Sydney BergmanFALL 2006 5

FLU!The morgue piled high withbodies. Pressure mounted asinfected patients inundatedthe hospital. Disoriented andalarmed, med students shouted,“Where is the ICU?” Theywore facemasks and protectivejackets designating theirroles on a team. When teammembers fell ill, remainingstudents, already hamperedby limited resources, diddouble duty, filling vacantpositions on other teams. Theintensity was only somewhatmitigated by the fact that thebodies were cardboard cutoutsand the scene at Scaifewas just a drill for respondingto an avian flu pandemic,part of a day-long pandemictraining program in May.—Alicia KoparJIM JUDKISName-DroppingThe School of Medicine was in very good company this spring.Ferid Murad, cowinner of the 1998 Nobel Prize in Physiologyor Medicine for discovering that nitric oxide can signal blood vesselsto relax and widen, thus lowering blood pressure, visited in April asa lecturer in the Senior Vice Chancellor’s Laureate Lecture series.The Distinguished Chair of Physiology and Medicine and directorof the Institute of Molecular Medicine at the University of Texas,Houston, spoke about a nitric oxide–related signaling pathway anddrug development.In May, Philip Beachy, professor of molecular biology andgenetics and a Howard Hughes Medical Institute investigator atJohns Hopkins University, also visited as a Laureate Lecturer. Beachyis a member of the National Academy of Sciences and a fellow ofthe American Academy of Arts and Sciences. He discussed how celldifferentiation and the growth and development of malignant cellsare influenced by what’s known as the Hedgehog signaling molecule,a protein secreted during embryonic development. (See theDean’s Message on p. 2 to learn how sheep and cyclopes fit into theHedgehog story.)After having a chance to learn more about the med school, Beachynotes, “The growth there is very impressive, as is the magnitude ofresources that are available. It seems pretty clear that Pitt is headedfor great things.”Risa Lavizzo-Mourey suggested to the Class of 2006 thattruly great things can come their way. The class had invited her to helpmark their graduation as the commencement speaker. Lavizzo-Moureyis president and CEO of the Robert Wood Johnson Foundation, a privatefoundation dedicated to improving Americans’ health.She told the graduates, “Each of you will have the chance toenrich the human condition and enhance the quality of life of peopleyou will come to know and love—and people you perhaps will nevermeet at all.” —JM6 PITTMED

CLOSERSKULLDIGGERYIn 2004, Adam Striegel, aUniversity of Pittsburgh undergraduateon a geology classfield trip near the PittsburghInternational Airport, picked up asoftball-sized rock that appearedto be a fossilized skull. He thoughtit should be examined further.Eventually, the fossil ended upin the hands of Carnegie Museumof Natural History paleontologistDavid Berman. He identified it asthe skull of a 300-million-year-oldtrematopid amphibian, evolutionarykin of the frog and thought torepresent a new genus and species.Researchers know of onlytwo other such fossils. So, how todivine the details of this find withoutrisking damage to the fossilby chipping away stone? Skull inhand, Berman recently approachedDouglas Robertson, associate professorof radiology and director ofthe Musculoskeletal Imaging andBiomechanics Laboratory at Pitt.Robertson took 1-millimeter-thinreadings of the rock-encased skullwith a 64-slice CT scanner—“Thelatest and greatest in clinicalscanners,” Robertson says. It differentiatedthe density of the rocksurrounding the fossil and the fossilitself. Robertson, an MD/PhD,took data from the scan and createda 3D image that can be flipped,spun, and turned any which way,so that paleontologists can closelystudy the prehistoric amphibianwhile keeping the actual fossilprotected.Priceless study subjects maybe routine to Robertson by now.He has used CT scanners to createa model of a 5,300-year-old funerarymask. He has served up x raysof dinosaurs. More typically, heemploys imaging technology todesign longer lasting and betterfunctioning replacement joints forpatients. —Joe MikschIMAGINGDOUGLAS ROBERTSONFALL 2006 57

INVESTIGATIONSExplorations and revelations taking place in the medical schoolThe special today in onelab: pork rich in omega-3fatty acids.SOME PIG!THE ALPHA AND OMEGAOF OMEGA-3 FATTY ACIDSBY JOE MIKSCH8 PITTMED

HELEN GRIFFINDragging a makeshift anchorin its wake, the brakelessmonorail hurtles throughSpringfield at speeds of up to 180 mph. Theconductor, one Homer J. Simpson—cartoonicon, Duff Beer connoisseur—awaits death.Suddenly, the anchor hits a snag—the LardLad donut shop sign. Latching onto an enormousrepresentation of a donut, the monorailcomes to a halt. Homer, his passengers, and therest of the town are safe.Reflecting, Homer utters these immortalwords: “Ah, donuts. Is there anything theycan’t do?”Replace “donuts” with “omega-3 fattyacids,” and you may be onto something. Workat the University of Pittsburgh shows that inaddition to omega-3s’ recognized benefit tocardiovascular health, these vital fatty acidsappear to improve mood and kill liver cancercells. Another Pitt project could help get thecritical fatty acids on the traditional Americanbreakfast table.Tong Wu’s lab has found that omega-3sappear to have an inhibitory effect on thegrowth of liver cancer cells. Wu, an MD/PhD associate professor in the Division ofTransplantation Pathology, says that for sometime, omega-3s have been known to inhibitcertain kinds of cancer cells.Wu and Kyu Lim, a PhD research scholarin the Department of Pathology, decided tolook at liver cancer cells, hoping to identifythe mechanism by which omega-3s fightcancer. They found that these essential fattyacids, which are not produced by the body,induced programmed cell death in liver cancercells. Additionally, they discovered thatomega-3 treatment reduced the presence ofbeta-catenin, a protein found in overabundancein tumors.Their findings, Wu says, show that omega-3s operate on at least two pathways as theycontrol the growth of liver cancer cells.As a control, the investigators treatedanother set of liver cancer cells with omega-6fatty acids, which are found in vegetable oiland are known to contribute to cardiovascularailments. The cells, like those treated withomega-3s, stewed in their fatty acid bath for12 to 48 hours. The researchers observed nosignificant changes to the cells.Wu and Lim plan to extend their researchinto animal studies.“This could be a good treatment forpatients who cannot tolerate other chemotherapeuticagents,” Wu says, “and may beused in combination with other therapies.”Sarah Conklin notes that omega-3snot only help the body, they can help themind. She is a postdoctoral scholar with theCardiovascular Behavioral Medicine Programin the Department of Psychiatry.Omega-3s are thought to alleviate symptomsof those with severe mental disorders. Yetlittle research has been done looking at whatrole they might play in sustaining the mentalhealth of adults.As a graduate student at Baylor Universityin Waco, Texas, Conklin worked on studiesshowing that anticonvulsant drugs reducedaggressive outbursts in men. But the sideeffects of such drugs, she says, were troubling.After she read a study equating a combinationof multivitamins and omega-3s with reducedaggression in prisoners, Conklin became interestedin learning more about how diet affectsmood and behavior.When she came to Pitt, Conklin and hercoinvestigators (including mentor MatthewMuldoon, associate professor of medicine)studied 106 healthy volunteers. Those withlower blood levels of omega-3s were moreimpulsive and had a negative outlook.Conklin believes that increased levels ofomega-3s balance out omega-6 fatty acids,which are known to have inflammatory effectson cells. Inflammation generates an immuneresponse, she says, and overactive immuneresponses have been implicated in various disorders,including major depression.Although none of these investigators isready to promise that omega-3s are a curefor anything, all say that they are potentiallypalliative for much more than cardiovascularailments. One day, consumers may be able togain such benefits from—of all things (andthis would appeal to Homer Simpson’s palate)—bacon.How so? Well, Pitt researchers have helpedgenetically engineer pigs to produce omega-3s typically derived from fatty fish and somenuts.Yifan Dai, associate professor of surgeryand member of the Thomas E. StarzlTransplantation Institute, was intrigued bythe work of Massachusetts General Hospitalresearcher Jing Kang. Kang had transferreda gene called fat-1 into mice, which resultedin their converting unhealthy omega-6 fattyacids into beneficial omega-3s.The MD/PhD thought that if he couldmake this work in larger animals—namelylivestock—perhaps we could get more omega-3 into our diet without having to rely onfish. In 2004, Dai began transferring thefat-1 gene into pig cells. But to get real, liveswine he called upon Randal Prather, leaderof the pig cloning center at the University ofMissouri–Columbia.Prather removed DNA from pig eggs andinserted Dai’s cells.He ended up with five pig litters. Onepiglet was found to be a fine producer ofomega-3s. Five of its clones became a breedingline of omega-3 rich pigs. The results of thiswork were published in Nature Biotechnologythis spring.“For agriculture, I think this will be veryuseful,” Dai says. “Not only for nutrition, butif these pigs are healthier than others [theiromega-3–rich bodies could ward off heartdisease], it may reduce costs for farmers.” Headds that for scientists, the animals could beexcellent research models.Omega-3–rich pork rinds are a way off,Dai says. First, the genetically modified pigsmust win FDA approval. And other questionsmay arise: Will palliative pork appeal totaste buds? Will people be hungry enough foromega-3s to eat engineered pigs? ■FALL 2006 9

PIECING TOGETHERPARKINSON’SA STUDENT RESEARCHER LANDS INTHE RIGHT PLACE AT THE RIGHT TIMEBY ELAINE VITONEAman moves slowly, stiffly, and yetwhen his limbs are at rest, theyquiver. When he wants to move,he can’t. When he doesn’t want to, he can’tstop. Cells in his brain are dying at an alarmingrate, and no one knows why. A Universityof Pittsburgh med student has positionedhimself well to help figure out why thiscellular slaughter happens in patients withParkinson’s disease.There are two basic forms of Parkinson’s—young-onset, a rare form affecting peopleyounger than 40 that tends to run in thefamily, and late-onset, a common sporadiccondition the incidence of which is higherin later life. The result is the same for either:progressive, wholesale destruction of cells inmany parts of the brain, including those thatproduce dopamine, a chemical critical to fluidityof motion.Thus far, at least two things are certain.For one, the disease has a genetic component.Young-onset cases have been linked to theinactivity of genes known as DJ-1, pink1, andparkin and to abnormal metabolism of theneural protein alpha-synuclein. For another,certain toxins such as pesticides and industrialchemicals play a role in late-onset Parkinson’s.Scientists believe that most Parkinson’s casesresult from a combination of environmentaland genetic factors; however, little is knownabout exactly how they work together to causecells to die.This summer, third-year Pitt med studentVipul Shah began a two-month breakfrom his rotations to conduct research underthe guidance of Edward Burton, assistantprofessor of neurology and of moleculargenetics and biochemistry. Shah hopes tohelp broaden our understanding of thecauses of Parkinson’s—and satisfy his scholarly-research-projectrequirement at the sametime. For the project, he’ll continue to meetwith Burton and other mentors throughouthis Pitt med schooling and eventually presenthis results to an executive committee offaculty members and deans.Shah reflects on the disease: “There’s a lotof work that needs to be done. … It’s unclearwhether every single [form of Parkinson’s] hasthe exact same pathogenesis. We’re trying tofigure out how they interrelate.”Burton says that the Pittsburgh Institutefor Neurodegenerative Diseases (PIND) is anideal setting for Shah’s explorations. “We’re inthe right place at the right time.”Historically, coming up with an animalmodel for Parkinson’s has been tricky: Howdo you create Parkinson’s in a rat if you don’tknow what causes it in humans? Previousattempts to simulate the disease involved poisoningthe animals with potent neurotoxinsthat target the dopamine-producing part ofthe brain. Because this method killed off allthe neurons at once rather than gradually, theprogression of the animals’ symptoms was afar cry from that of humans with Parkinson’s.In the past two decades, several labs haveshown that Parkinson’s patients carry defectsin their mitochondria, a key discovery that ledPIND director Timothy Greenamyre to, in asense, build a better rodent. As a faculty memberat Emory University in 2000, Greenamyre foundthat when animals are chronically exposed to lowlevels of the pesticide rotenone (which is toxicto mitochondria), they develop abnormal brainpathology and progressively worsening symptomsthat mirror those of human Parkinson’spatients. His rotenone model—which six yearsago was the first confirmation of the longand widely held suspicion that pesticides caninduce the disease—is ideal for testing questionsBurton’s lab is exploring.Shah will use genetically engineered viruseson Greenamyre’s rats to explore these questions:How do genetic and environmental factorsrelate in Parkinson’s? Can you prevent or treatenvironmentally induced Parkinson’s by overexpressingparkin, DJ-1, or pink1 or by removingalpha-synuclein?Shah likes the way Burton is open to input.The two meet regularly, but how Shah goesabout obtaining usable data is largely up to him.For example, at first they debated whether Shah’sproject should concentrate on in-vitro or invivoexperiments. “I am really interested in thebehavioral experiments that may allow us to seeactual Parkinsonian behavior in rats,” says Shah,“so that is the path we are pursuing.”Perhaps giving Shah that freedom is easyenough. Shah worked in an Alzheimer’s lab asan undergraduate at the University of Florida,which was where he first developed an interestin neuroscience.“He’s incredibly independent as students go,”Burton says.■ALFRED PASIEKA / SCIENCE PHOTO LIBRARY10 PITTMED

COURTESY U.S. DEPARTMENT OF ENERGYSENIORCAN SCIENCE END THEM?BY JIM SWYERSAs we age, many of us begin tonotice that our memories aren’twhat they used to be. We forgetthe names of people we’ve just met, regularlymisplace our glasses or car keys, or lose theability to store and retrieve numbers the waywe used to.We often dismiss these instances of forgetfulnessas “senior moments” and move onwith our lives. We accept that a progressivedecline of memory, as well as other cognitiveand motor abilities, is inevitable, like deathand taxes. It seems there’s nothing we can doabout it.However, according to research being conductedby Etienne Sibille, a PhD assistantprofessor of psychiatry at the University ofPittsburgh, such notions may not be accurate.His work is demonstrating that many longheldconceptions about aging, particularlythe notion that irreversible and generalizedMust our brains progressivelydecline with age?One Pitt researcher is usingDNA microarrays like thisto find out about the genesbehind brain aging.MOMENTSbiological decline accompanies normal aging,are dead wrong.Using DNA microarrays—a technologythat allows researchers to read the activity, orexpression patterns, of all 22,000 genes in eachcell simultaneously—Sibille was surprised tolearn that only a small number of genes areinvolved in the biological decline that can beassociated with an aging brain.Sibille’s team made this discovery by analyzingpreserved brain tissue samples from autopsiesof 39 people who ranged in age from 13 to79. The analysis found changes in gene expressionpatterns in only a small subset—about 10percent—of the total genes in the brain cells.According to Sibille, these findings suggestthat the aging process in the brain is limited inits scope: “We thought that the genetic signs ofaging in the brain would be more complicatedand involve many more genes. Because only alimited number of genes are involved, it meansthat aging in the brain is a selective event.”More importantly, Sibille believes the processmay be malleable. Indeed, he and his colleaguesfound different patterns of age-relatedgenetic changes in glial and neuronal cells—the two main types of brain cells. Genes inglial cells became more active with age, andgenes in neuronal cells became less active.“The fact that it is limited to a relativelyfew number of genes and possibly cells, andthat the effect is different in the types of braincells involved, may allow us to delay and,possibly, alter the aging process in the brain,”Sibille says.It’s a bold thought. Yet Sibille believes hehas evidence that such a scenario is possible.When his laboratory researchers began examiningage-related genes they’d identified, theyfound that many of the genes were involvedin the regulation of mood. By disabling, or“knocking out,” the same genes in mice, theydiscovered one that, when absent, initiated theaging process. It turns out that the gene, calledHtr1B, codes for a receptor that interacts withthe neurotransmitter serotonin.“It has long been known that there arechanges in the serotonin system with aging,which are considered [to contribute] to thedevelopment of age-related mood disorders,such as depression,” notes Sibille.“When we knocked out the gene for thisreceptor in mice, it caused an early onset ofage-related behavioral deficits.”Sibille says that by manipulating this receptor,his lab showed it was possible to “alter thetrajectory of age-related events.”Much more work remains to be donebefore the full story of aging in the brain isknown. Meanwhile, Sibille’s lab is continuingto disable genes in mice that appear to beinvolved in brain aging and observing the subsequentbehavioral changes. The investigatorsalso are using microarrays to see what happensto the rest of the genes when some of theseage-related genes are disabled.“We need to keep deciphering what thesegenes are telling us to get the completepicture of what is happening at the cellularlevel,” he says.He believes that in the not-too-distantfuture it may be possible through lifestyle ordrug interventions to delay the onset of thebrain-aging process in humans. Even a delayof this process by as little as a few years woulddramatically lower the percentage of elderlypeople living with cognitive or other brainrelateddeficits, he suggests.■FALL 2006 11

Three of Pat Strobel’s five grandchildren—11-year-old twins Nicholas and Samantha (left and right) and Tommaso, 8—sit on the porch swing where Patused to “interview” the children with a video camera, asking them questions like “What’s your name? What do you want to be when you grow up?”12 PITTMED

FEATUREIN THE WORLD OF TRANSPLANTATION,MOST SECOND CHANCES BEGIN WITH A LOSSPHOTOGRAPHY | CHARLEE BRODSKYTEXT | ELAINE VITONENEXT OF KINRiight now, more than 92,000 people are on the national waiting list for a vitalorgan transplant. Their best chance for survival is probably a rare and tragic turnof events for another family. Last year, UPMC (including Children’s Hospital ofPittsburgh) and VA Pittsburgh Healthcare System performed 686 transplantswith organs from donors who appeared to be alive but were actually brain-dead.These people were still breathing with the help of a ventilator and yet already gone. Such casesamount to 2 percent of all deaths, and among them, only about half result in organ donation,despite the critical need.Without a donor card or designation on a driver’s license, it is up to the next of kin to makethe sensitive decision about organ donation as they say goodbye to a loved one who appears to bemerely sleeping. Three Pittsburgh-area families who gave the gift of organ donation in this wayconsented to share their stories with us here. They remind us of how some remarkable secondchances began with a loss.Like with the Strobel family. Back when Raymond, Bonnie, and Herb Jr. were growing upin West Homestead, Herb Sr. used to sell his blood to afford Christmas gifts. Mounds of giftsby the tree, their Uncle Casey filming the kids’ faces—Christmas meant more to their mom, PatStrobel, than anything.Three years ago, Pat was hospitalized for congestive heart failure. “She wasn’t on the phone crying,”says Raymond. “She called just to say we had to postpone Christmas Eve because something came up.”According to the family, Pat was treated with blood thinners, inadvertently opening a floodgateof bleeding in her brain. Cerebral hemorrhage runs in the family—it killed Pat’s mother, grandmother,and uncle years ago. Then, seven months after Pat’s death, her younger brother, Casey,followed. Both Pat and Casey became organ donors.The Strobels are the kind of family who, with little notice, will assemble three generationsaround a table to tell you about Pat and Casey. They’ll tell you about when Pat used to listen tothe scanner to make sure her two police-officer sons were okay. “I don’t like that dispatcher,” she’dsay. “She’s not nice to you.”They’ll tell you about the scores of Kaufmann’s employees who showed up for Casey’s funeral,remembering their coworker with story after story. “He would meet this one lady every morningat 5 a.m. just to open the door for her and carry her bags upstairs,” Bonnie says. They’ll tell youhow upset Pat was when Herb Jr. got his first tattoo, and it didn’t say “Mom.” In January 2003,he inked three new letters into his arm.FALL 2006 13

Jim and Jan Eddy in the family’s home in North Huntingdon. The couple light a candle for their son Mike every night.14 PITTMED

Now as Jan and Jim Eddy reminisce in the living room of their North Huntingdonhome, they laugh about the things that used to frustrate them. When Mike was little,he’d stash food around the house—eggs on the bed, fish sticks in the dryer. When hegot older, it was his socks. Once, they found a pair in Jim’s tackle box.Mike’s older brother, Adam, and younger sister, Angela, worked hard to keep their gradesup. “Mike didn’t care,” says Jan. “He was there to socialize, play sports. He had 16 years offun. He’d say, ‘Mom, chicks dig me.’”The accident happened 10 years ago this summer. Mike had been so good that week thatJim said he could stay out until 11:30. A friend was driving him home to make curfew whenanother car ran a stop sign, broadsiding them.Months after the accident, Jan found a pair of socks in the living room couch. “I said,‘Now I get it.’ This was not to drive me crazy while he was living. It was to make me laughafter he was gone. I sat down and just cried. I laughed and cried.”left: After their son Mike died, the Eddys begancollecting boy angels. This one was a Christmasgift from a woman who received one of Mike’skidneys. above: Jim Eddy holds the chain hisson kept attached to his wallet.FALL 2006 15

16 PITTMEDFrank Holby stands in the doorway, looking into his daughter Michelle’s old bedroom, now empty, as heand his wife, Judy Holby, prepare to move. Judy holds a “Get Well Soon” balloon, still inflated 19 yearsafter Michelle’s friends left it at the family’s door while Michelle was in the hospital.

FEATURETHOMAS STARZL SAYS TOLERANCEIS ON THE OTHER SIDE OF REJECTIONBY CHUCK STARESINICBREAK ONTHROUGHCONTINUED FROM OUR MAY ISSUEResearchers at theThomas E. StarzlTransplantation Institutebelieve that decadesof laboratory researchand clinical experiencewill yield a systematicway to help transplantpatients tolerate theirnew organs with littleor no medication. Oneavenue of investigationreaches into the depthsof the sea for answers.Oddly enough, jellyfishthat live on the backsof hermit crabs haveoffered clues.In 1986, Thomas Starzl flew to Japan for a chance at a fewdrops of an experimental drug known by the unwieldy designationof FR 900506. The response to his inquiry was,essentially, “Maybe.” After Starzl’s formal request, a Japanesepharmaceutical executive immediately jetted off to London to talkthings over with officials from a British company with which hisfirm collaborated. Starzl, then a Pitt professor of surgery, waited inJapan for a definitive answer.He was 60 years old. He had a reputation for boundless intellectualand physical stamina, not to mention unparalleled skill and driveas a surgeon. He was the man who had made liver transplantationa reality when many had insisted it could not be done. But now hefelt chronically fatigued. He was becoming careful instead of bold,he would later reflect in his 1992 memoir, The Puzzle People. Andhe privately wondered whether this drug was better left to someoneelse to champion or reject.ILLUSTRATION | JACOB THOMAS AT DECO ZONEFALL 2006 19

In Pittsburgh, transplant patients carriedon the all-consuming struggle to live.Drained of color and vigor, jaundiced, incoherent,and perhaps even comatose, theywaited for organs without which they woulddie. Families wrestled with the knowledgethat their prayers could only be fulfilledthrough someone else’s tragedy. The luckyones weathered the aftershocks of transplantation:Their tissues were inflamed as a result ofincisions and the stitching together of foreignblood vessels and ducts. More ominously,their white blood cells — roving protectorsof the status quo that are born in the bonemarrow — diligently attempted to seek out,identify, and destroy any cell from the donororgan so carefully stitched into place.It was on behalf of these patients, andall those to come after, that Starzl, now aDistinguished Service Professor of Surgery,waited in Japan for one-hundredth of an ounceof FR 900506. Starzl’s patients in Pittsburghwere being treated with cyclosporine then,a drug that Starzl had begun experimentingwith in 1979. When he first demonstrated tothe medical community that a careful blendof cyclosporine and steroids could control theassault of the immune system upon a donororgan, the field of transplantation took anenormous leap forward. Survival rates surgedupward. Unfortunately, cyclosporine wassomewhat toxic. It could lead to serious kidneydamage or outright failure. Some patientsin early trials without steroids had developedwhite blood cell cancers. Starzl avoided suchcatastrophes through the addition of steroidsand by administering the lowest dosage possible,but some patients rejected their neworgans despite the help of cyclosporine.Standing in the lobby of the Fukuoka Hotelone week after his arrival in Japan, Starzl gothis answer. At the end of a slow, almost ceremonialdiscussion translated by a Japanesesurgeon, Starzl was entrusted with a vial of liquidFR 900506. The contents would not havefilled a thimble. He rushed back to Pittsburghwith it and with the promise of more.Like cyclosporine, FR 900506 (which nowgoes by the names FK 506 and tacrolimus)suppressed a subset of white blood cells thathelped the immune system target the neworgan for destruction. Researchers at otherinstitutions cautioned Starzl that it was prohibitivelytoxic — a probable dead end, theytold him. But Starzl had patients who wererunning out of options, and he believed that,like cyclosporine, this drug could work if carefullycombined with steroids.Eventually, tacrolimus was approvedfor patients who had rejected multipleorgans — they were facing either another riskytransplant or death. Starzl’s first was a womanrejecting her third liver in eight months. Thencame a man rejecting his fifth liver in fouryears. Tacrolimus stopped rejection in bothof them. After two years, seven of the first10 people who’d switched from cyclosporinestopped and reversed a deadly immuneresponse. Patients with failing transplants cameto Pittsburgh from around the world.Tacrolimus is used widely to this day, yet it’slong been clear that suppressing the immunesystem with highly toxic drugs is an imperfectway of making transplants stick. Patients whoare saved by new livers or kidneys are forced toendure side effects like debilitating pain, nausea,tremors, excessive hair growth, high bloodpressure, diabetes, and tumors. You could survivea liver transplant at 35, but die at 50 fromthe side effects of your medication.When Starzl came to Pittsburgh in 1981, hisgoal had been to prove that organ transplantswere possible on a large scale, especially bloodyand technically challenging liver transplants.He had accomplished that in Pittsburgh. Now,there was a new peak to bag: tolerance — a statein which an organ would be accepted withoutimmunosuppression.Tolerance was not complete fantasy.As early as the 1960s, Starzl had takenpatients off immunosuppression on a hunch.A few showed no ill effects and remained drugfree.Those who showed signs of rejection wentback on their meds. Yet the science of immunologyhad no clear explanation for why onepatient could achieve tolerance and anotherwould fail to. To add to the mystery, it wouldlater become clear that patients who’d hadtransplants in the 1960s were more likely toachieve tolerance than those transplanted later,say, in the 1990s. While surgeons had gottenbetter at doing transplants and had foundbetter drugs to stop rejection, their patientsseemed less likely to achieve tolerance.Starzl walked out of the operating roomone day in 1990 and decided he wasn’tgoing back. He was done salvaginghealthy organs from those unfortunate enoughto no longer need them. Done standing allnight sewing livers into those who would diewithout them. He found it a great relief.With more time on his hands, Starzl decidedto scratch a mental itch he’d had for years concerninghis most successful patients. In 1992,he invited 30 of the world’s longest-survivingtransplant patients to Pittsburgh. Among themwere a man who had lived 29 years with someoneelse’s kidney and a woman who had lived23 years with a transplanted liver. The 30 wereon various levels of maintenance immunosuppression,and at least one was drug free.According to the prevalent immunologicaltheories of the day, their donor organs wereislands amid hostile seas. To keep the immunesystem from swelling into a tidal wave, doctorscalmed the seas with drugs. Cells from a donororgan that dared to set foot off the island inviteddestruction. Starzl suspected there was moreto the story than that. He asked his patients toprovide blood and tissue samples from severalparts of their bodies, even biopsies of variousorgans. He then enlisted the help of Pitt expertsin, among other techniques, the sort of DNAfingerprinting that allows criminal prosecutorsto identify an individual from the DNA in atiny trace of blood or a hair.Whom did Starzl want to identify in thesevarious bodily tissues? The donor — long deadbut for a transplanted organ pulsing along ina foreign body. Starzl found what he was lookingfor. A woman who had undergone a successfulliver transplant years ago, for example,had the cells of the donor throughout herbody, not just in her secondhand liver. A populationof the donor’s white blood cells had“hitchhiked” on the transplanted organ andmigrated to her hands, her heart, her lungs.These migratory hitchhikers had not met withdestruction. They were quietly swimmingin her bloodstream and nestling into herinternal organs.Not everyone in the fields of immunologyand transplantation accepted what Starzl hadfound. It went against the accepted understandingof organ transplants: The body would neveraccept an organ that did not come from anidentical twin, so the immune system must besuppressed indefinitely.Starzl described what he saw as “chimerism.”In ancient Greek mythology, the chimera wasa fantastical creature with the body of a lion,the head of a goat, and the tail of a serpent.Starzl’s patients exhibited microchimerism,harboring living cells that had originated withtwo individuals.He pointed out that chimerism had beenwitnessed for decades in successful bone marrowtransplants.In cases of leukemia, for example, thepatient’s marrow and blood cells — including20 PITTMED

the white blood cells that are the workhorsesof the immune system — are wiped out withradiation and replaced by cells produced by thedonor’s transplanted bone marrow. When thenew cells circulate throughout the body andtake up the work of the recipient’s immune system,the patient is a chimera. Starzl suggestedthat successful organ transplantation fit thesame paradigm, though they had been thoughtof as different phenomena for decades.Before he became scientific director ofthe Thomas E. Starzl TransplantationInstitute and before he’d even met Starzl,Fadi Lakkis had heard about his theory.“But my view of chimerism,” says thePitt professor of surgery and of immunology,“was like the view of most people outthere —skepticism, because this Tom Starzl isfamous for pushing the envelope to a limitthat most mortals are not willing to go to.And like everybody else, and being naïve at thetime, I thought, ‘This is very interesting,’…but I never really thought about it seriouslybecause the view out there was — I’ll tell youhonestly — that’s Tom Starzl again, trying to saysomething that’s not possible.”Lakkis points out that this is the same thingthe medical community said decades ago whenStarzl advocated for liver transplantation — oncethought impossible and now an accepted curefor liver disease.Lakkis, who recently moved to Pitt fromYale University, is still settling into his officeat the Starzl Institute. He is tall and friendly,is easy to engage in conversation, and becomesdownright animated when discussing how theimmune system works or might work. (It’shumbling to realize how much remains tobe discovered about how the immune systemworks.) Lakkis, an MD, was a practicingclinical nephrologist and director of transplantmedicine at Yale, but his affinity has long beenfor scientists who can happily spend years inthe lab investigating the immune system andcan pass hours pontificating about its evolution.In the course of his laboratory investigationswhen he was at Emory University, Lakkishad unwittingly found evidence to supportStarzl’s theory.Lakkis first visited Pittsburgh in 1999 togive a talk on his immunology research.“It was a meeting of the minds,” says theonce-skeptical Lakkis, explaining that he andStarzl discovered they were thinking aboutimmunology in very similar ways. Lakkis presentedresearch on a molecule produced bythe immune system— interleukin-2(IL-2). It was wellknown that IL-2 wasinvolved in rejection.When the immunesystem identifies aforeign invader suchas a transplantedorgan, IL-2 activatesT cells (a type ofwhite blood cell)that recognize andattack the invader.Lakkis and his teamexperimented with amouse that did notproduce IL-2.“To our surprise,the organs stillrejected,” he says.“So we hypothesized that T-cell activationis required for achieving tolerance. And thereason it is required is it prepares the cell fordeath. IL-2 activates the cell but also plantsthe seed of death in it, which makes sense,because you don’t want immune responses tokeep going and going and going. You wantT-cell activation, lymphocyte activation, butyou want to ensure that this dies off. … Youcan get very bad infections as a child, andyour lymph nodes can get bigger when youget a sore throat, but then they shrink back.So there are things that regulate the immunesystem. What we found is that what activatesit also regulates it.“It fit very nicely with what Starzl had beentrying to tell the world,” says Lakkis. “You’vegot to let the immune system get activated.Let this battle go on, and that’s how you willeventually get tolerance. Instead, in the clinic,people were going around and giving heavyimmunosuppression to patients from the getgo,which definitely protects the organs, butthen you cannot get off immunosuppression,because once you take them off, those T-cellsare still there. So the only chance to get the T-cells to die out is to let that battle happen.”Chimerism, Starzl says, is not just a discoverythat cells had migrated from transplantedorgans and taken up residence in far corners ofthe recipients’ bodies. The very phenomenondemonstrated why there had to be a mechanismfor tolerance.“We’re all exposed to viruses all the time,”says Starzl, offering an example. “Eighty-fivepercent of the population carries antibodiesTwo for one: Starzl’s successors,Fadi Lakkis (left) and AmadeoMarcos (right), now lead theinstitute’s efforts in researchand surgery, respectively.to cytomegalovirus and other hepatitis viruses.I’m swimming in antibodies — you probablyare, too — against the B-virus or C-virus.”If the immune reaction had as its goal thedetermination to get rid of every last virus,Starzl says, “85 percent of the world would bedead. So the immune system has found a wayto switch the immune reaction off, and thatis tolerance.”At Pitt, Lakkis is setting up a lab that willallow him to explore another great mystery ofimmunology that may help scientists understandtolerance: the innate immune system.In his lab, the research subjects are tiny jellyfishof the genus Hydractinia. These are notfree-floating jellyfish. In the wild, some speciesgrow on the backs of hermit crabs and arecalled “snail fur.” In Lakkis’ lab, they ride glassslides submerged in saltwater.Jellyfish do not have the highly evolvedimmune systems of humans and other largeanimals. They have no lymph nodes, no whiteblood cells — what immunologists call theadaptive immune system — but they recognize“self” and reject “nonself.” When two jellyfish,sponges, or other primitive invertebratesattempt to live side by side on the same surface,they may even begin to fuse together intoone larger organism. That’s when the battle ofthe innate immune systems begins. If the individualsare of the same species, and especiallyif they are related and have genetic similarities,they may eventually tolerate one another andbecome, essentially, one fused organism withliving cells from two — a chimera. The descriptionis reminiscent of what happens when aFALL 2006 21

COVER STORYMAKE LIKE ASALAMANDERSalamanders andnewts do it, so whynot us? Pitt’s StephenBadylak coordinatesa team that hopes tolearn how to regrowa mammalian digit.They believe theseamphibians can showthem how.LIMBS ON DEMAND?BY JOE MIKSCHYou really don’t need to think much about thisone: A pig’s bladder is a very good thing tohave … if you’re a pig.But if you’ve amputated the tip of your pointer fingerabove the first joint while handling a model airplane as itspropeller was still spinning, perhaps the organ isn’t the firstthing to look for in your medicine chest.However, when a Cincinnati man in his 60s lost thepointy part of his pointer in the manner described above, hesought out the University of Pittsburgh’s Stephen Badylak,ILLUSTRATION | CATHERINE LAZUREFALL 2006 23

understanding that, in his particular case, onemight come in handy. One of Badylak’s colleagueshad told the man that the doctor haddone impressive feats with pig tissue.Badylak is a research professor in theDepartment of Surgery with a secondaryappointment in bioengineering at Pitt. He hasa PhD, a DVM, and an MD and directs theCenter for Pre-Clinical Tissue Engineeringin the McGowan Institute for RegenerativeMedicine.Badylak placed a piece of biologic scaffolding—derivedfrom a pig bladder by strippingthe organ of cells—on the injured finger.A similar and commercially available materialhas been used in half a million patients toregenerate tissue, including those who wouldlike to regrow rotator cuffs, Achilles tendons,and other soft tissues. Could Badylak’s experimentalscaffold cultivate an entire tip of afinger? He didn’t know.Six weeks later, the man who once faceddeformity was made whole again. Moleculeswithin the scaffolding drew stem cells to theamputation site. The cells differentiated andmultiplied, and the fingertip—bone, bloodmouse regenerating a functional digit—muchin the same manner a salamander or newtregenerates a limb. The grant could be worthup to $15 million throughout four years.Badylak’s former boss, retired PurdueUniversity President Steven Beering (MD ’58),believes the group has an able coordinator.Beering is a member of the University ofPittsburgh Board of Trustees, and was recentlyappointed chair of the National ScienceBoard, which serves as the science adviser tothe president and Congress and oversees theNational Science Foundation. He says thatBadylak is “the most innovative researcherI’ve ever met. I’m a great admirer of his workand his research.”Badylak began meeting with team members—expertsin places as far-flung as Lowell,Mass., and Salt Lake City, Utah—two yearsbefore they received any funding.“We’ve got two developmental biologists,a great classical cell biologist, an excellentmolecular biologist, and an immunologistwho’s spent her life understanding the role ofthe immune system in regeneration,” he says.“If we’re smart enough, we’ll combine the“Salamanders are champions of regenerativeability,” says Simon.When a salamander loses a limb, molecularsignals compel the surrounding tissueto produce cells that divide and accumulateat the wound site. The resulting cell mass,called a blastema, specializes as it matures,forming all the necessary components ofthe missing limb. Here, an adult humanwould form a scar.“Salamanders replace lost structureswithout forming a scar,” Simon says, “butthe process is slow. Our wounds heal fast,and the expense is a scar.”“That’s the default healing mechanismin adults,” says Badylak. “Fetuses don’t formscar tissue; they regenerate.”Likewise, doctors can perform heart surgeryon fetuses in utero without risking lossof function because of scarring. Badylakthinks adult humans lose their regenerativepotential in maturity because the genes thatgovern the process in fetuses and infantshave been turned off.Adult humans do have some regenerativeabilities, producing red blood cells, liverThe fingertip—bone, blood vessels, nerves, skin, fingernail—grew back.It looked perfect and was perfectly functional.vessels, nerves, skin, fingernail—grew back. Itlooked perfect and was perfectly functional.Then Badylak did the same for a Bostonman in his 70s who nipped a fingertip witha band saw.This is the stuff of salamanders andnewts, a pair of amphibians who have theability to regenerate lost limbs. When it happensin a person with the aid of the structuralmaterial that helps support and organize cellsin a pig’s urinary bladder, it’s the stuff of sciencefiction.“The chances of this happening,” Badylaksays, pausing, “I mean, it’s really rare. I’mnot saying it’s impossible, but nobody wouldhave predicted it [working]. Now, it didn’t goacross a joint, so we didn’t regrow a joint, andthat’s going to be a real challenge.”It’s a challenge Badylak, with five otherscientists from across the United States,has accepted. The group is equipped witha $3.7-million, 12-month grant from theDepartment of Defense’s Defense AdvancedResearch Projects Agency (DARPA). Theresearchers hope their efforts will result in aright talents and discover things we neverwould have discovered on our own.”Hans-Georg Simon is a developmentalbiologist, an assistant professor of pediatricsat Children’s Memorial Research Center andNorthwestern University in Chicago, and amember of the DARPA team. He expects theteam’s diversity will result in “great quantumsynergy.”So where does the A team begin? With thesalamander.One day, a salamander—let’s call himJimbo—is minding his own businessnear a little stream. Nice andpastoral. Calm. But danger lurks in theweeds. A garter snake attacks, lunging at ourlittle mudpuppy. Jimbo’s leg gets trapped,then the bone snaps, the muscle and skin tearoff, and he scurries to safety on three legs.A couple of months later, a four-leggedsalamander is lolling about near the samestream. Looks a bit familiar, no? Well, heshould. That’s Jimbo with a full complementof legs. How the heck did that happen?cells, and skin cells continually. Comparedto a fetus or a salamander, though, this isbush league.“We’re asking ourselves what genes getturned on and off differently between anewborn and an adult,” Badylak says. “Is itpossible to reverse the gene expression patternto that of a fetus, at least temporarilyand at the site that you’re interested in? Ifwe can do that, maybe we can reprogramthe local cells that we get [at an amputationsite] to think that they need to form a newlimb.”Simon says that understanding theregenerative ability of animals such as thesalamander is key to tapping into humanregenerative potential.Cells that form a blastema, he says, seemto have control over what they become.They are aware of where they are in thesense that they can tell if the salamander losthis front leg or back. They can tell whetherthe amputation is near the shoulder or foot.They know the structure of what it is theyare to replace.24 PITTMED

FALL 2006 25

GLOVED HAND WITH SCAFFOLD: COURTESY J. MURPHY. JUNCTION DEVICE: COURTESY T. GILBERT.“They never make anything extra, andthey never leave anything out,” says Simon.“We’re trying to follow nature,” he adds.“Nature has millions and millions of years ofexperience. And us human beings, what dowe have comparatively? Nothing.” People arejust starting to understand the mechanismsbehind regeneration, he notes.A class of genes called TBX is linked tothe blastema’s special knowledge. In salamanders,these genes are, obviously, active. Inmice and adult humans they are not. Whena certain TBX gene malfunctions in a mouse,the mouse doesn’t grow forelimbs. When it’smutated in the human genome, problemscan range from missing thumbs to truncated,flipper-like arms.But check that bit about mice being nonregenerative.One transgenic mouse surprisedscientists by making itself whole again.above: Stretched between two glovedhands, this piece of biologic scaffolding,derived from a pig’s bladder, isready to be used as a kind of trellisupon which new tissue can grow. left:The upside-down funnel is a similarpiece of scaffolding built to help thebody repair the junction between theesophagus and the stomach.One of the ways scientists markindividual mice in the lab for identificationis to pierce their ears. Whensmall holes were punched in the earsof a breed known as MRL mice, DARPAteam member Ellen Heber-Katz, a professorin the molecular and cellular oncogenesis programin the Wistar Institute in Philadelphia,noticed that the holes filled in.“This isn’t supposed to happen,” Badylaksays with a laugh.But it did give the team an idea. “Oneof our approaches is to take a regeneratingspecies [salamanders], a partially regeneratingspecies [MRL mice], and a nonregeneratingspecies [conventional mice] and look at commonthings among them and the differentthings.”Susan Braunhut’s lab at the University ofMassachusetts Lowell has taken a major rolein sorting out the commonalities and differences.A professor of biological sciences,Braunhut is attempting to identify the biologicalfactors, genes aside, that cause cells toparticipate in blastema formation.Being able to harness such a moleculecould translate to therapies that eliminatescarring as well as regenerate tissue.Braunhut’s work, Badylak says, is vitalfor the team to meet its first-year goal:DARPA has challenged the team to identifyat least one molecule that shows bioactivitytoward a progenitor cell, a cell that participatesin blastema formation.“We need to know the regulators of theseprocesses,” Badylak says. “We need to knowwhat molecules recruit these cells as well aswhich ones regulate gene expression.”Braunhut has made inroads in this areaon her own. Three years ago, she built a“smart” bandage. It’s an extracellular matrixenriched with specific growth factors thatspeed healing in specific types of wounds.This accomplishment serendipitously led toher collaboration with Badylak.“The work was funded by DARPA, andmy program manager had been workingwith Steve,” she says. “He knew about mybasic research into matrix and growth factorsand told me to call [Badylak]. He saidwe were meant to meet. We did, and by thetime we left, we had agreed to collaborate.”The pair found out about a DARPAopportunity and began searching forother researchers to join them, includingBraunhut’s former postdoctoral advisor,Lorraine Gudas, Revlon PharmaceuticalProfessor of Pharmacology and Toxicologyand chair of pharmacology at CornellUniversity, and regenerative gene expertShannon Odelberg, assistant professor ofinternal medicine and of neurobiology andanatomy at the University of Utah.On their own dime, the six met inWashington, D.C., and began to pursuethe DARPA money with tenacity. “Whenthis project came, it resonated with thisteam,” Braunhut says. The idea had been“cooking” for some time with each of them,she notes.Wrapped up in Braunhut’s work isanother mystery to solve. Some membersof the team have already identified possiblefactors that propel progenitor cells to woundsites. What they don’t know is whether thesecells are derived from the adjacent tissue atan amputation site or are drawn from bonemarrow. Could be both, Badylak notes. Andonce all this is understood, there’s still thequestion of how to stimulate a regenerativeresponse rather than a scar tissue response.26 PITTMED

In 12 months, the team is expectedto isolate a molecule that causes cells tomigrate to a wound site and cause those cellsto multiply and differentiate. The mysterymolecule also must be genetically relatedto a blastema cell. “That’s a lot of work,”Badylak says.But Braunhut is ready to go with assaysthat will help distinguish molecules inBadylak’s biologic scaffolding or in Simon’ssalamanders that beckon cells or tell themto commit to becoming nerve, bone, ormuscle.If the team meets with success here, thenext goal is to form a blastema in a nonregenerativeanimal. From there, a functioningdigit on a mouse. And, further down theline, this team or another group of scientistswill attempt to regenerate a fully functionallimb on an adult human being. Of course,doing all this requires understanding notjust the individual pieces of the puzzle, butalso how all the components fit together.Braunhut is humbled but unbowed:“If five or 10 years ago you were to saywe’d be able to get a very complex threedimensionalstructure to regrow in an adult,I’d say we wouldn’t be able to do it.“Today I say we might be able to do it.We’re at the edge of what’s in the realm ofpossibility.”The other team members also talk withcautious optimism. The six senior investigatorsthink that not only are they well preparedin their individual areas of expertise,they’re getting the right kind of supportfrom the right kind of funding agency.Typically, Badylak says, once investigatorsreceive grants—from, say, the NationalInstitutes of Health—they’ve got fundingfor a finite number of years, do their work,publish what they can, and file periodicprogress reports throughout.DARPA, he says, is different: “They giveyou extremely challenging problems and say,‘If we take away all the barriers, if we eliminatemoney as a limiting factor, we expectproductivity. That’s why each of the principalinvestigators on this project [has] gottenmore money for this grant than they’ve gottenfor any single activity in their career.“Basically, they’re buying our attention.”The team holds an hour-long biweeklyconference call during which every teammember plays a part, even when travelingabroad. A DARPA officer—who’s also a scientist—participatesin each of these calls.The calls help DARPA assess the team’sprogress. If the team doesn’t meet its goals, itcould lose funding.“But it also means that they know whatthe roadblocks are, what problems we have,what accomplishments we make,” Badylaksays. “I’ve worked on DARPA projects before.If things don’t progress, they say, ‘What’s theissue? How can we help?’”A lot of good can come from the attempts,notes Simon: “Even if we fail to make a digitregrow in a mouse, we could revolutionizehow we deal with wounds in the clinic. Toachieve better wound healing, less scarring,would be a major advance in medicine.”When officials at the defense departmentfound out about Badylak’ssuccess in using biologic scaffoldingto regrow the fingertips of the men fromCincinnati and Boston, they wanted to seewhether the technology could help woundedsoldiers.“We told them it’s not ready for primetime,” Badylak says.But the DOD pressed, saying that anyfinger regrowth—even a couple of centimeters—couldgreatly improve a woundedsoldier’s quality of life.“They’re saying if you can get extension ofwhat’s left of a finger, the finger can appose[think a pinching motion] the thumb,”Badylak says, allowing a wounded vet to performsimple tasks such as putting a car key inthe ignition or picking up silverware.From the Civil War through the firstGulf War, the ratio of injured to killed soldiersstood at about 2.5 to 1, according toBadylak. In Afghanistan and Iraq, the DODreports, the ratio is more like 9 to 1.Because of advances in body armor,Badylak says, “Soldiers can withstand impactthat would have killed them before, and thearmy is saying, ‘What are we going to dowith all these injured? What can we do toimprove their quality of life?’”So now Badylak is the principal investigatorin two DOD-funded clinical trials set totake place in San Antonio, Texas, before theyear is out.Between five and 10 soldiers at BrookeArmy Medical Center will participate in atrial that will attempt to regrow portions oftheir fingers. Twenty others at the hospitalwill take part in a second trial examiningthe effectiveness of biologic scaffolding inregrowing skin.Doctors will apply scaffolding to thedonor sites of burn patients who have hadskin grafts, with the hope of accelerating thehealing process at that site.Why not the burn site itself? The donorsite is cleaner and easier to work with, notesBadylak.“If this works, that will give us the confidenceto go to the primary wound,” he says.Badylak’s lab is a noisy place. More thantwo dozen people work there, whichis part of the reason. Another is theperpetual hum coming from the conveniencestore–style cooler against the wall.Inside it are two clear plastic containers.One sits on an orbital shaker, the other on arocking platform. Pale blobs slosh about ineach. The blobs going in circles are pig bladders,the ones rocking back and forth are dogpancreases.“It’s a little gross,” Badylak admits. “Thereason they’re so white is that the tissue nolonger has cells in it.” The organs are beingwashed in a solution that’s stripping them ofeverything but the matrix, the material thatcells hold onto as they form tissue. It’s thismaterial that Badylak used to help regeneratethe fingertips of the men hurt by the bandsaw and model plane.Two aisles over from the cooler, instrumentsare at work screening for the moleculeswithin the matrix that prompt the kind ofbiologic response that allowed the men’sfingers to become whole again and maycontribute to the DARPA project’s goal ofregenerating an entire digit.Badylak rattles off the list of questions thisscreening process could help answer: Why dostem cells accumulate? Why does biologicscaffolding have antimicrobial and antibacterialproperties? Why do cells proliferate inthe presence of the matrix? “We’re developingassays to measure all of those things—proliferation,chemoattraction,” he says.Later, Badylak talks more reflectively: “Ifwe can understand how to regrow a digit, whycan’t we use those same principles to regrowa kidney for patients on dialysis? Or a pieceof the heart that was damaged by a heartattack? Or how about a lung for patients withemphysema?”“That’s what’s gotten me really excited,”he says, running his finger along a sectionof scaffolding formed like a trachea. “We’regoing to learn principles that will make manythings possible.”■FALL 2006 27

FEATUREA PITT RESEARCHER AND A FAMILY IN CENTRALPENNSYLVANIA ARE LEARNING FROM THE SAMERARE DISEASE | BY ERICA LLOYDDIFFICULT GIFTSImagine having cerebralpalsy, cystic fibrosis, musculardystrophy, and AIDS—andbeing highly susceptible tocancer. That’s what it’s liketo have ataxia telangiectasia(A-T). This rare disease haspointed scientists toward aDNA damage control pathwaycentral to good health. left:Young human cells containno detectable DNA damage(column 1). After more than60 divisions (column 2), aprotein called ATM (green)detects where both strands ofDNA have been severed. ATMmarks the breaks by labelinghistone (red; it appears yellowwhen shown with ATM).Zapping the cells with ionizingradiation activates nearlyall the ATM protein (column3), which is responsible forkicking off the DNA repairprocess. Children with A-Tdon’t have this vital protein.Twelve years ago, Pam Fickel of Carlisle, Pa., gavebirth to a beautiful baby boy. Blond, blue-eyedDouglas Jr. appeared to be the picture of perfecthealth. But after she brought Douglas home, thethen 31-year-old Fickel started to think something “wasn’tright.” Her baby moved his hands and fingers in strangeways. And little Douglas was drooling so much, she’d have tochange his shirt four, five, maybe six times a day. Because hisformula stained the shirts, she found herself throwing soiledones away and buying T-shirts in bulk from the thrift store.“I knew this wasn’t teething,” she says, looking back.Fickel shared her concerns at Douglas’ 9-month checkup.The doctor and others told her she was being overly cautious.Before Douglas Jr. was born, Pam and Doug Fickel had lostJane, their third daughter, to hydrocephalus. “I was being overprotective,they told me,” says Fickel.IMAGES | COURTESY C. BAKKENISTFALL 2006 29

At a year, she tried again. Please listen tome. No one heard.By the time Douglas’ 15-month well-babycheckup came up, he was falling down 30times a day. He’d knocked himself unconscioustwice. The doctor watched Douglastake a few steps. He saw an eager boy toddlinghis way across the room and was aboutto pronounce him fit as a fiddle.Fickel stopped him.“I want to strip him down to his diaper,”she announced.Then Fickel suggested the little boy walkfor the doctor again—this time all the waydown the hall.Without the cloak of cloth on the child,the doctor could see how Douglas’ gaitwas different from that of other boys andgirls. The toddler waddled forward, armsraised and contorted like duck wings, backarched, wrists limp, pointer and middle fingersspread out as though he was “signing aK badly,” his mom recalls. This was how healways walked.The doctor wanted to schedule a scanimmediately. It could be a brain tumor, hesaid. It was Thursday, and the MRI peoplecould fit Douglas in that day.Fickel, who knew her boy had been livingwith whatever this was all his short life, saidthe appointment would have to wait untilTuesday. That’s when Doug Sr. was returningfrom his hunting trip, and the couple hadvowed they’d never again put the other inthe position of hearing what they suspectedwould be a bad diagnosis alone.“When I found out about Jane, I was bymyself,” says Fickel.Fickel held her breath all weekend, hopingshe’d made the right decision. Tuesdaycame and the doctors found nothing. MoreMRIs at the medical center in Hershey followed.Douglas was poked, prodded, andscanned for months, then years. The doctorsalways came up empty.When Douglas turned 4, Fickel cancelledhis appointments. Her son was walkingpretty well. He wasn’t falling down. Couldhe be getting better? At least he’d have sometime away from all those tests.At 5, red spider veins appeared in Douglas’eyes. When the Fickels went back to thedoctor, he said, “The monster has reared itshead.”He wasn’t speaking of the Fickels’ sweetson. The doctor was speaking of a rare diseaseknown as ataxia telangiectasia, or A-T. WhenDouglas turned 4, his growth had outpacedthe progression of his disease, so he seemedto get better for a while. But then the diseaseasserted itself again.Ataxia refers to a patient’s lack of motorcontrol owing to progressive neurodegeneration.(The doctors in Hershey couldn’tsee anything on the brain scans becauseDouglas’ brain probably appeared normal.)Telangiectasia (pronounced teh-LAN-jick-TAY-sha) refers to the fine spidery burst veinsthat often appear on the eyes and ears ofchildren with the disease.The burst veins are harmless. But most ofthe other symptoms of this childhood diseasearen’t.A-T gradually cripples the developmentof the cerebellum so that as children with thedisease grow older, they lose motor control.They have difficulty walking, and by theirsecond decade, they are probably in wheelchairs.Eventually, their eyes won’t stay on apage, so reading, as well as writing, becomesnext to impossible. It’s hard for them totalk. They are in constant motion—even asthey sleep—so they are often very thin. It’snot unusual for a bit of food to end up in alung and cause pneumonia, which is particularlydangerous for them because A-T alsocompromises their immune systems. It is anexhausting disease.The Fickels felt a strange sense of reliefon hearing the diagnosis, as awful as it was.No more MRIs. And at least they knew whatthey were up against.Imagine having cerebral palsy, cystic fibrosis,muscular dystrophy, and AIDS—that’sanalogous to what these kids and their familiesare dealing with. A-T–afflicted childrenare also highly susceptible to cancer. They are1,000 times more likely to develop malignanciesof the blood than the general population.Making matters worse, radiation therapycauses awful burns and is likely to kill them.Why does it seem their own bodies have itin for them? It comes down to a gene calledATM, first cloned in the ’90s by an Israeliresearcher. The ATM cloning was “one ofthe last great” traditional cloning effortsbefore the Human Genome Project, saysChristopher Bakkenist, assistant professorof radiation oncology at the University ofPittsburgh.Only one in 40,000 children get A-T.But it turns out, the biology behind this raredisease is relevant to all of us.Since the gene was cloned, scientists haveDouglas Fickellearned that the ATM protein sits at thetop of the DNA damage repair pathway. It’sin charge of getting our bodies to respondappropriately when the most profound kindof DNA damage occurs—that is, when bothstrands in the double helix are completelysevered.We all experience double strand breaksthroughout our lives. An x ray at the dentist’soffice induces them. Cosmic rays probablydo. More importantly, the process our cellsroutinely go through to use oxygen resultsin double strand breaks. They are insidious.The good news? Unless you have A-T, yourbody knows how to cope with these lesions.It will either repair the problem or arrangefor the cell to kill itself so it doesn’t do somethingunwelcome as a mutation.But Douglas and others with A-T don’thave the ATM protein. So their bodies aresubjected to the whims of rogue and mutantcells. Imagine trying to keep a Fiat runningwithout a mechanic to fix and replace partsas they inevitably break. You’d probably needa push now and then.When Douglas gets tired, he gets lotsof help from his family, friends, and community.He was on a baseball team duringelementary school. He didn’t make manypractices though—they were too taxing. Justsitting on the bench without losing his balancewas a struggle. Sometimes at a gamehe’d sit in the outfield, and if a ball came hisway, he’d yell to a teammate, “Could you getthat for me?”He learned to put his energy toward reallyimportant things. Like sliding into base. He’dsay to his mom, “I’ve got to slide! I’ve got toslide!” That was the coolest thing to do, afterCOURTESY P. FICKEL30 PITTMED

all. But the chance never seemed to presentitself—until one time, when he was about8. Douglas got all the way to third base andtagged it. Then he announced, “Okay, I’msafe. I’m safe, right?!” When the ump andother players agreed, he took several stepsback toward second and slid into third.“He was the happiest child in the world.He wouldn’t let me wash his uniform,” saysFickel.She kept hoping that Douglas would bethe exception, that he wouldn’t end up in awheelchair. He played kickball at the partyfor his 9th birthday. By 10 he couldn’t; hedepended on his wheelchair. Douglas, now11, thinks it would be a good idea for him tomeet the Steelers’ Bill Cowher and give himsome ideas for plays. He loves skateboarderTony Hawk. His best friends are his older sisters,Sam and Emma. The world stops whencountry music star Toby Keith is singing.Douglas still plays baseball, but now herides an electric retrofit bike to get aroundthe bases.He hasn’t been able to read since thirdgrade, but he has a sharp memory. For aspelling test, he and his classmates were toldto each pick 10 or so words from a list of244. They would each be tested on the wordsthey’d chosen.Fickel got a call from the teacher.“Douglas wants to do all 244,” she said.“Let him.”Guess who scored highest for accuracy.Maybe you’ve heard this annoyingadage from a wise grandmotherlytype: Difficulty teaches us thingswe might not otherwise have known aboutourselves. In the world of biomedical science,it’s not unusual for researchers to study ananomaly to learn about what healthy bodiesdo. A-T offers a particularly revealing moleculardance. This harrowing and rare diseasehas pointed scientists toward vital clues tounderstanding the mechanisms involved incancer and DNA repair.Christopher Bakkenist has never metDouglas Fickel. But he, too, spends his dayswith A-T, though he doesn’t have the illness.Bakkenist, who was raised in the middle ofEngland, studied and trained at the Universityof London, Oxford University, and St. JudeChildren’s Research Hospital in Memphis.Last year he joined the faculty at Pitt. He is38, reserved, a still talker, and gravely seriousabout his research. His work is inspired bythe idea that scientists can “actually make animpact and change the way people look at theworld.” If you ask how, he’ll say the path issimple: “You put the diseased children first. Assoon as we put ourselves first, we’ve lost it.”Before coming to Pitt last year, he workedas a postdoc with prominent ATM researcherMichael Kastan at St. Jude. By then, scientistshad identified a number of importantproteins that the ATM pathway activated,including a tumor suppressor called p53. Thisprotein itself is profoundly powerful.“It’s mutated in 50 percent of all 100 kindsof cancer,” notes Robert Abraham (PhD’81), vice president of oncology for WyethResearch in Pearl River, N.Y., who studiedpharmacology at Pitt.“There’s a very solid argument out therethat if [cancer] patients don’t have a p53mutation, they have a mutation somewhereelse in the p53 pathway. It’s like a necessarymilestone a cancer cell has to pass to becomea fully malignant cell.”Several labs identified other importantproteins that are set off downstream of ATM(which is a kinase, so it sets off chemical reactions).But no one could figure out exactlyhow ATM sounded the alarm that DNAdamage was taking place, notes Abraham.“One of the burning questions in thefield was, How does ATM actually respond todouble strand breaks?”During his fellowship, Bakkenist createda sensitive reagent that allowed him to seein detail what was happening during theATM response. Bakkenist and Kastan werethen able to show that ATM is made up ofat least two inactive molecules. When bothDNA strands break after a blast of ionizingradiation, ATM releases two single, and nolonger dormant, ATM molecules. The scientistsalso described the unexpected transfer ofphosphates that takes place within the proteinitself before the single ATM molecules sendphosphates downstream to activate importantproteins like p53. Those downstream actorsstop the cell cycle to allow repair to occur orto set in motion the extinguishing of unrepairablecells.A news article in Nature notes that Kastanand Bakkenist revealed that “the sensitivity,extent and speed of the ATM response aretruly astonishing. Doses of irradiation thatcause only a few [double strand breaks] ina human cell activate the majority of ATMwithin minutes.”It was a seminal finding, says Abraham:“The failure of this pathway explains thewhole syndrome.”But how is ATM tipped off to a doublestrand break?Chromosomes are made up of buildingblocks called chromatin that include DNAand proteins. Kastan and Bakkenist showedthat changes to chromatin structure let ATMknow there’s a problem.Bakkenist can see how such findings couldopen the door to better cancer therapies:“If you can inhibit the [ATM] protein,you may be able to increase the efficacy ofDNA damage therapy, including radiotherapy,in human cancer. The other approach is,if you can activate ATM artificially, you maybe able to temporarily activate p53 as well. Ifyou transiently activate p53, before the canceris actually developed, you may be able to usethe p53 to kill off precancerous cells.“So you may be able to use it as a prophylacticcancer therapy, to prevent humancancer.”ATM has a sister protein that sits next toit at the top of the DNA damage pathway. It’scalled ATR (ATM related) and orchestratesthe response to another brand of DNA damage—thatcaused by UV light. This responseblocks the progression of DNA replication.(Mutations that pass through this pathwaycan show up as skin cancer.) Bakkenist is nowinterested in studying ATR, and Abraham isoptimistic about what he’ll find:“This is really important work. I think thatChris is better positioned than just about anybodyelse to pursue this work. These are verylarge proteins that pose many challenges.”Because her son is at risk of developingcancer, Pam Fickel carefully monitorshis lymph nodes to make sure theydon’t grow larger.She had uterine cancer a few years ago.Fickel is a carrier of the mutated ATM gene(as is her husband; both parents must be carriersfor a child to get the disease). There’s aschool of thought that says if she had beengiven radiation therapy or a drug that mimickedstrong doses of ionizing radiation, theresults could have been fatal.Fickel knew about this risk only becauseof Douglas’ strange disease. So Douglas, justby being himself, may have saved his mom’slife.■for more information, we recommendthe A-T children’s project: www.atcp.orgFALL 2006 31

ATTENDINGRuminations on the medical lifeAN HONOR AND APRIVILEGETHE STORY OF A MEDICAL STUDENT | BY THOMAS CONLON32 PITTMED

JIM BURKEThe following is an edited version of ThomasConlon’s graduation address. Conlon (MD ’06)served as president of his class and delivered thespeech at May’s graduation ceremony.You did it … with hard work andsupport from friends and family,the University of Pittsburgh, one ofthe finest medical schools in the nation, openedthe door for you to attain your dream. Andthere you are, day number one. You are amazedby the diversity of your classmates—not necessarilyin race or gender as we are so ingrained totake note of—but rather their dynamic personalities,how they carry themselves so differentlybut with such presence.And you sit down in your sparkling newwhite coat and hear Dean Levine discuss thehonor and privilege of medicine. You’re hardlyable to keep your jaw from hitting the floor.The painted portraits surrounding you, thecameras flashing from proud parents above, theoath taken. Your dream is realized. What anhonor and privilege it would be.And first year rolls on, and you’re finding that,while you were a star in college, you are strugglingto remain at average here. Or maybe you’reat the top of the heap, and nobody can imaginethe strain of living up to continued expectations.And you’re finding that you aren’t talking to yourfriends from home as much as before because,well, frankly, they just can’t understand. Andyou’re in a long-distance relationship, which isstrained because you know that for every houryou aren’t studying that likely means anotherpoint off your test, and you can’t afford that. Butof course your boyfriend or girlfriend doesn’tunderstand that. Or you go home to your spouseand, though you thought it would be a welcomething to have something outside of the medicalworld, you find you’re becoming more detached.And your parents call, but they don’t understandthe world of medicine, or conversely one of themis a practicing physician and keeps telling youthat she “understands.” But she’s not here, andshe doesn’t know.The end of second year comes, and you haveto sit for boards. Mr. Levitt has warned you ofan eight-week schedule of insanity, which youscoff at and discard for your own schedule. Thatturns out to be 10 weeks of even greater insanity.This one test determines whether you can bean orthopod, a neurosurgeon, whether you canmatch where you want. The test comes andgoes. Immediately afterward you drive out toa friend’s cabin in the middle of nowhere, andyou sit with a fishing rod between your legsand a glass of milk at your side, finally able tofeel as though you’ve escaped. That’s when ithits you: You don’t really know if you like theperson you’re becoming.In third year your clinical rotations begin,and you don’t know the computers, and you’renot answering the attending’s questions right,and you’ve got to go into the patient’s roomright now to get a full history and physicalto turn in by morning, and you sit down atthe bedside, shuffle some papers, look at yourwatch then lift your head up—and your eyesmeet. Looking back at you are the eyes of amale, a female, a white collar, a blue collar, ano collar, a broken hip, a stage-four cancer, a10-year-old, a 100-year-old. And wham. Youonly knew vaguely this feeling when applyingto medical school. You tried your best to put itinto words when asked, “So why do you wantto become a doctor?” Here it is, and wordsdon’t suffice. Those eyes read of fear, of realizedmortality, of experience. They want your help.At that moment, you recognize your responsibility.And you’re partially stunned because youwant nothing more than to embrace it—thewhole thing. At that same moment, you gainsome understanding of the first two years, howthey provided you with the intellectual andemotional framework you’d need.It’s 4:30 in the morning and you wake upand you’re tired but ready to roll. And you hopon the bus and you look at the worn faces ofthe janitors, the security guards, the line cooks,and you realize the difference between peoplewho go to work and what you get to do. Andyou get off the bus and the driver says, asalways, “Have a nice day,” ’cause that’s whatthey do in Pittsburgh. And you get off and,even though it’s Wednesday and summer and4:45 in the morning, blurt out, “Go Stillers,”because that’s what they do in Pittsburgh.And you walk into the building and, asa potted plant is to someone with pica, so isthat morning cup of Joe to you that you’rebrewing in the conference room. And you’re inChildren’s and you watch as 2-year-old Sally,who came in with a septic joint, waddles withher back to you, her little hand completelyengulfed by her father’s massive paw, she inonly a diaper. And you can’t help but smile.And you’re at the VA, and there’s old manDawkins with his IV pole and his back to youin the hall, gown on, but he is in neither diapernor any sign of undergarments, and again,you can’t help but smile. And you’re on orthorounds, and you just benched 250. And you’rein surgery and you—cut that fascia really well(or whatever gets you surgeons excited). Andyou find that attending who loves to teach anddoes it in such a way that you actually learn,and you really want to go home and read tocontinue the conversation at another level.And it’s 5:30 p.m. and you’re getting outa little early because it’s short call. All yourpatients are tucked in; you’re thinking aboutdinner; then your pager goes off. You dialthe number and on the other end of the lineyou hear, “This is UPMC quality control. Wehave a report of inappropriate touching of oneof our elderly female patients and would likeyou to swing by our office immediately.” Yourstomach drops. You try to figure out whetheryou even have an elderly female patient inyour care when you start hearing childish gigglingover the other end of the phone. “Realfunny … Thomas.” It’s the standard happyhour page, the bat sign that someone hada rough day and needs to unwind, and youwouldn’t mind a quick glass of milk yourself.As your friends roll into the bar, youremember you have to call one of your buddies,so you stand outside and get in touchwith Joe—one of your closest pals from college.He asks about school, and you tell himthat it’s brutal, torture, all the words you’veused in the past with him during your infrequentconversations. But he knows you loveit. And for the first time in months, you stopyourself midsentence and ask—for real thistime—“Joe, how the heck are you?”When you get home, you check the alarmto make sure it’s set for … oh, four hoursfrom now and turn on the radio to makesure the volume is high enough. Then youare reminded by the sports commentator thatyes, it’s true, the White Sox really did win theseries and are world champions. And you can’twait to wake up tomorrow.Doctors, sharing this with you has been theabsolute highest honor and privilege. ■FALL 2006 33

DISTURBINGDEVIATIONSJUST ANOTHER DAY IN THE FRONTAL LOBEBY KATRINA FIRLIKKatrina Firlik (Res ’02) is a neurosurgeonpracticing in Greenwich, Conn. In her recentlyreleased memoir, Firlik recalls stories from herdays training at the University of Pittsburgh,including the scarce details she was able to learnof “Mr. Doe”—a patient who died within 24hours after entering the hospital with multipletraumas. She admits he was someone she mighthave otherwise forgotten but for a drop of blooda bad cut on his scalp left on her white coat.The drop served as a reminder of the manthe rest of her busy week. She writes, “If everypatient left a stain, a resident’s life could verywell become an unbearable mess. A stain everyonce in a while, though, can probably help keepus human. That realization must have been onereason I kept a journal during my training. Iknew I would otherwise forget along the way,partly because there was too much to rememberand partly because I might want to forget.” Thefollowing is another memorable “stain” Firlikshares in her book.Ihad the privilege of working withstellar pediatric neurosurgeons whosereputations brought patients in fromall over the neighboring states and beyond.We saw the most complex, most bizarre,and most tragic of cases. Because modernmedicine has become so good at treatingevery symptom, I was continually amazed atthe children who were able to survive so longwith so little brain function, with mothers,fathers, and hired help attending to everyneed and hauling around what amountedto miniature ICUs in their minivans. Ibecame comfortable with conflicting emotions,thinking both “How touching!” and“How strange!” at the same time.I had to perform a spinal tap on a childwho had been neurologically devastated atbirth. While I had the needle in his back, hismother mentioned that it was a good thingthat she had forgotten to bring his Passe-Muirvalve (an insert for a tracheostomy that allowsa patient to talk). She explained that, this way,he would remain quiet through the spinal tap.I expressed some surprise that he actually hada Passe-Muir valve. I knew that his brain wasnot capable of speech or even thought. “No,you’re right, he’s completely nonverbal,” sheconfirmed, very matter-of-fact and even smiling,“but he does make noises.” This was notthe first time I made a mental note to avoidmaking assumptions.At one point, late into my senior residentyear, I was rudely awakened to the fact thatI had become perhaps too jaded in dealingwith the tragedies of neurological devastation.I had become overly accustomed to our clinics,going from exam room to exam room,one featuring a mother waiting quietly whileshe casually suctioned her daughter’s tracheostomy,another featuring a 12-year-old boywhose legs were so rigid and contorted thatit was nearly impossible for his mother tochange his diaper.I walked into yet another examining roomafter checking the patient’s chart. It was abrand-new consult: 18 years old, cerebral palsy,spasticity. Okay, okay, I’ve seen this before, Ijust need to get a good historybefore my attendingwalks in. Efficiency is key.I looked at the patient for asecond: very skinny, specialwheelchair, arms contracted,head support in place,mouth hung open. It wasclear I wasn’t going to getthe story from him, so Iturned to the parents, myback toward the patient,and started to take downthe history. The mother’s account went back 18years, recounting her pregnancy in detail. Shewas helpful but a bit long-winded, so I jumpedin after a few minutes with some pointed questions.As a rule I make an effort to let people finishtheir stories before I butt in, but sometimes Ihave to break my own rule. There were a numberof other patients waiting, and I didn’t really needto know all the specific dietary details.As I sat, dutifully recording the list of medications,allergies, and operations, my mentorwalked in. I cringed. I was hoping to haveat least the history done so I could presenthim with a nice summary. He sat down onthe examining table, the only seat left in thecramped room. After introducing himself, hesurveyed the compact scene—the patient, theparents—and then focused his gaze back on thepatient. After what seemed like several, almostuncomfortably quiet, seconds, he looked thepatient in the eye and asked: “So, when did yougraduate from high school?” The young man’sface lit up like I had no idea it could.My mentor had noticed something I’d missed.The patient was wearing a large high school ring,so large that it looked a little silly on his bonyfinger. His body, far more than his mind, hadborne the brunt of his cerebral palsy. He wasa proud, beaming high school graduate. Hismother pointed out the specialized computer,attached to his wheelchair, thathelps him communicate. Forthe remainder of the visit Isat in the corner, duncelike,humbled by the enormity ofthis ring.■Excerpted from Another Dayin the Frontal Lobe by KatrinaFirlik. © 2006 Katrina S. Firlik,MD. Reprinted by arrangementwith The Random HousePublishing Group.34 PITTMED

MATCH RESULTSCLASS OF 2006ILLUSTRATION ALISON ZAPATA / PHOTO CIDDEANESTHESIOLOGYDesciak, MatthewMilton Hershey Medical Center/Penn State, Pa.Hache, JohnUPMC Medical Education ProgramHall-Burton, DeniseUPMC Medical Education ProgramHsieh, VincentStanford University Programs, Calif.Lee, JeromeUPMC Medical Education ProgramMalec, ChrisCase Western/University Hospitals, OhioMuhly, WallisUPMC Medical Education ProgramNguyen, JessicaBrigham & Women’s Hospital, Mass.Steinfoff, StephanieHospital of the University of PennsylvaniaYuditskaya, SusanNew York Presbyterian Hospital—ColumbiaEMERGENCY MEDICINEBeierle, JessicaUPMC Medical Education ProgramBetz, AmyUPMC Medical Education ProgramFerguson, ErikaUniversity of Chicago Hospitals, Ill.Landry, JonathanAlbert Einstein Medical Center, Pa.Miller, DavidGeisinger Health System, Pa.Shum, LeoUPMC Medical Education ProgramTobias, AdamUPMC Medical Education ProgramWeinberger, LaurenHospital of the University of PennsylvaniaFAMILY PRACTICEDacal, KirstenUPMC St. MargaretForrest, PaigeUPMC St. MargaretMilne, HollyUCLA Medical Center, Calif.Torres, CarlosUPMC St. MargaretINTERNAL MEDICINEAfshar, KiaJohns Hopkins Hospital, Md.Altman, RichardMt. Sinai Hospital, N.Y.Balfour, PelbretonUniversity of VirginiaBrown, DanielUPMC Medical Education ProgramCharlton, GeorgeUniversity of VirginiaDePaul, ScottWilford Hall Medical Center, Lackland AFB, TexasDiederich, EmilyNorthwestern McGaw/NMH/VA, Ill.Downing, TriciaEinstein/Jacobi Medical Center, N.Y.George, EzminUniversity of Chicago Hospitals, Ill.Geynisman, DanielUPMC Medical Education ProgramHong, EricUCLA Medical Center, Calif.James, DavidNew York Presbyterian Hospital—CornellKim, Young-SinCalifornia Pacific Medical Center, San FranciscoLevinthal, DavidUniversity of Michigan Hospitals—Ann ArborLin, EleanorMayo Graduate School of Medicine, Minn.Madathil, RonsonCase Western/University Hospitals, OhioMuldrow, LekishaUPMC Medical Education ProgramPatel, KartikThomas Jefferson University, Pa.Prentice, NikkishaHospital of the Universityof PennsylvaniaRanganathan, AnjanaBoston University MedicalCenter, Mass.Rockacy, MatthewUPMC Medical EducationProgramSallam, KarimStanford UniversityPrograms, Calif.Scheers-Masters, JoshuaSUNY HSC Brooklyn, N.Y.Vitale, MatthewBrigham & Women’sHospital, Mass.INTERNALMEDICINE—PEDIATRICSConlon, ThomasUPMC Medical Education ProgramKrier, JoelRush University Medical Center, Ill.Patel, SapanUniversity Hospital, Cincinnati, OhioINTERNAL MEDICINE—PRELIMINARYBrennen, PeterUPMC Medical Education ProgramVilsaint, KevinMaimonides Medical Center, N.Y.INTERNAL MEDICINE—PRIMARYDallaPiazza, MichelleHospital of the University of PennsylvaniaMavrich, KateRhode Island Hospital/Brown UniversityMuo, IjeomaEinstein/Montefiore Medical Center, N.Y.Sinton, TobyUniversity of Washington Affiliated HospitalsMAXILLOFACIAL SURGERYYeung, AlisonUPMC Medical Education ProgramNEUROLOGICAL SURGERYAbla, AdibBarrow Neurological Institute, Ariz.Grosvenor, AshleyStanford University Programs, Calif.Jian, BrianUniversity of California, San FranciscoLehmann, EmilyUniversity of Michigan Hospitals—Ann ArborTormenti, MatthewUPMC Medical Education ProgramNEUROLOGYReichman, JordanNew York Presbyterian Hospital—CornellStephenson, SharisseTufts University School of Medicine, Mass.NEUROLOGY—PEDIATRICSSundararajan, KripaNew York UniversityOBSTETRICS/GYNECOLOGYByno, AshleyChristiana Care Health Services, Del.Donnellan, NicoleUPMC Medical Education ProgramDryden, EmilyOhio State University Medical CenterJacobs, StephanieEinstein/Montefiore Medical Center, N.Y.Reinhart, GretchenMedical University of South CarolinaWarner, SarahUniversity of Rochester/Strong Memorial Hospital, N.Y.OPHTHALMOLOGYAli, TofikAlbert Einstein College of Medicine, N.Y.Joshi, AmarUPMC Medical Education ProgramReese, MatthewMedical University of South Carolina, CharlestonWu, EricUPMC Medical Education ProgramORTHOPAEDIC SURGERYAboka, AlexanderUniversity of New Mexico School of MedicineAmorosa, LouisNew York Presbyterian Hospital—ColumbiaRabuck, StephenNorthwestern McGaw/NMH/VA, Ill.Schulz, JacobAlbert Einstein Medical Center, Pa.Westrick, EdwardUPMC Medical Education ProgramOTOLARYNGOLOGYDunklebarger, JoshuaUPMC Medical Education ProgramSneshkoff, NikolausTripler Army Medical Center, HawaiiSun, GordonUniversity Hospital, Cincinnati, OhioTobey, AllisonUPMC Medical Education ProgramPATHOLOGYBiller, ElizabethOhio State University Medical Center, ColumbusUchin, JeffreyCleveland Clinic Foundation, OhioPEDIATRICSAbikoff, CoriChildren’s Hospital of Pittsburgh of UPMCBeck, AndrewCincinnati Children’s Hospital Medical Center, OhioBrown, CrystalUniversity of Maryland Medical Center, BaltimoreCampfield, BrianChildren’s Hospital of Pittsburgh of UPMCCastiglioni, CynthiaNorthwestern McGaw/CMH, Ill.Gokhale, JanakiThomas Jefferson University/Dupont Children’sHospital, Pa.Haupt, AliciaChildren’s Hospital of Philadelphia, Pa.Jerardi, KarenCincinnati Children’s Hospital Medical Center, OhioKiger, JamesMedical University of South CarolinaKim, NahmahChildren’s National Medical Center, Washington, D.C.Rice, CarrynPalmetto Health Richland Hospital, Columbia, S.C.Srinath, ArvindJohns Hopkins Hospital, Md.Stenger, ElizabethChildren’s Hospital of Pittsburgh of UPMCWelter, JacquelineNorthwestern McGaw/CMH, Ill.PHYSICAL MEDICINE &REHABILITATIONJohnson, JeffreyNorthwestern McGaw/RIC, Ill.PLASTIC SURGERYKeith, JonathanUPMC Medical Education ProgramPSYCHIATRYAsare, AkuaJackson Memorial Hospital, Fla.Walters, JulianUniversity of Arizona Affiliated Hospitals, TucsonRADIATION ONCOLOGYDeFoe, SarahgeneUPMC Medical Education ProgramRADIOLOGY DIAGNOSTICChang, WilsonStanford University Programs, Calif.Gold, MichelleThomas Jefferson University, Pa.Lynn, KarenWilliam Beaumont Hospital, Mich.Shah, VinilUniversity of California, San FranciscoRESEARCH/ADVANCED STUDIESBataille, FeguensResearchHarewood, PeterAdvanced studies/MPHRyan, AlexanderAdvanced studies/PhDSwihart, AndrewAnesthesiology researchSURGERY—GENERALBrown, NefertitiSUNY HSC Brooklyn, N.Y.Bucher, BrianBarnes-Jewish Hospital, Mo.Erickson, AndrewWashington Hospital Center, Washington, D.C.Falcone, JohnUPMC Medical Education ProgramHsu, AlbertBeth Israel Deaconess Medical Center, Mass.Johnston, W. CoryUniversity of Utah Affiliated Hospitals, Salt Lake CityNeal, MatthewUPMC Medical Education ProgramNordman, CoryUPMC Medical Education ProgramSiriratsivawong, KrisNaval Medical Center, San Diego, Calif.Suydam, ErinMedical College of GeorgiaTorres, ArturoNaval Medical Center, San Diego, Calif.Trivedi, PremalCase Western/University Hospitals, OhioWashington, ChristopherAllegheny General Hospital, Pa.PRELIMINARY SURGERYCampbell, BrianWashington Hospital Center, Washington, D.C.Forbes, JonathanJohns Hopkins Hospital, Md.Gallup, TheresaUniversity of Texas—San AntonioUROLOGYBassett, JeffreyUCLA Medical Center, Calif.The Class of 2006 is offand running. Fifty-eightpercent of graduatesmatched to residenciesin one of the 15 mosthighly ranked academicmedical centers in thecountry (includingUPMC). Of this year’sgraduates, 40 percentchose primary carespecialties, 33 percentpursued surgical specialties,and 22 percentselected hospitalbasedspecialties.FALL 2006 35

ALUMNI NEWSCLASS NOTESRuth Snyder Masters andRaymond Masters meton the first day of class.’30sOne of only two women in the classof 1935, Ruth Snyder Masters(MD ’35) says she picked herfuture husband of 64 years, thelate Raymond Masters (MD ’35),out as “one of the nice ones” ontheir first day of medical school.The two married in 1936, thoughthe infamous flood of that yearleft the groom tending to floodvictims and delayed their weddingby two weeks. Ruth Masters’ career in family practicespanned seven decades. She estimates she delivered3,200 babies, including more than 200 home deliveries.She saw patients at her East McKeesport officeand McKeesport Hospital. In 1979, she became the firstwoman to be elected president of the hospital staff.Since retiring four years ago at the age of 88, Mastershas remained an active member of the hospital’s ethicscommittee.’70s AsMichael Wusylko (MD ’77) never imagined that hea medical student at Pitt,would stay so close to one of his favorite professors,infectious disease specialist and Pitt professor GeorgePazin (MD ’64). Wusylko, an internist, currently shareshis practice in Cranberry, Pa., with Pazin’s son JohnPazin. As a clinical preceptor, Wusylko welcomes Pittmedical students into his practice each year for threeweekrotations. Last year, Pitt med students honoredhim with the Award for Excellence in Clinical Precepting.’80s Frightened, desperate, and ill, lupuspatients travel from as far away as the Middle East andSouth America for a diagnosis. Pittsburgh is where manyof them finally learn the cause of their debilitating andunpredictable symptoms. Lupus is notoriously difficultto diagnose. On average, a lupus sufferer waits fouryears before the disease is recognized. Susan ManziGARY WILLIAMSTOXIC AVENGER(MD ’85, Rheumatology Fellow ’91), cofounder and codirectorof the Lupus Center of Excellence at Magee WomensHospital and Pitt associate professor of medicine, developeda blood test using complement C4 positive proteins that willhelp physicians detect lupus. Her research shows that theprotein binds to red blood cells during lupus flare-ups. Withthis test, physicians will be able to better diagnose the diseaseand start appropriate treatment.Donald Yealy (Emergency Medicine Resident ’88, AirwayManagement and Out of Hospital Cardiac Arrest Fellow ’89)is professor and vice chair of emergency medicine at Pitt. Inthe past 15 years, he has won five teaching awards, includingthe 2001 National Teaching Award from the AmericanCollege of Emergency Physicians. Most recently, Yealyreceived the Hal Jayne Academic Excellence Award fromthe American Society for Academic Emergency Medicine forwork that helps emergency room physicians determine theseverity of community-acquired pneumonia and heart failure.He is currently working with Pitt professor of medicineMichael Fine (Chief Medical Resident ’87) and Pitt professorof critical care medicine Derek Angus (Critical Care MedicineFellow ’91) on ways to identify and treat acute pneumoniaand sepsis in the emergency department.Steve Burton (Internal Medicine Resident ’89,Hematology/Oncology Fellow ’92, Radiation OncologyResident ’95) is at UPMC Shadyside. Burton uses “hightechtoys” like linear accelerators to treat cancer. Themachines precisely target tumors and destroy them withradiation, saving patients from invasive surgery. Burton,who is a clinical assistant professor of radiation oncology,is conducting research to demonstrate the effectiveness ofimage-guided radiation treatment for tumors.’90s Dave Thomson (Emergency MedicineResident ’90) came to Pitt hoping to be on the front lines ofAsk Gary Williams (MD ’67) what he considers to be the most dangerous substancethat humans ingest, and you’ll receive a surprising answer: food.“Think,” he says, “every plant is a little chemical factory with substancesto fight off its natural pests.” He explains that these toxins also can affect humans.Other natural toxins run rampant as well, including dangerous molds on peanuts andcorn, which contribute to the high incidence of liver cancer in humid Asian climates.Williams, professor of pathology at New York Medical College, discussed otherfood-borne dangers as a delegate in the World Health Organization’s ExpertCommittee on Food Additives’ June meeting in Rome. An expert in toxicologicalpathology and chemical carcinogenesis, Williams researches everything from offthe-shelfconsumer products to pretrial pharmaceuticals. New York Medical Collegerecently recognized him with the 2005 Dean’s Distinguished Research Award for hisinnovative methods and discoveries.Williams recalls a recent incident in the United Kingdom in which six volunteersnearly died during a drug trial. His work attempts to prevent such things from happening.It includes discoveries such as an antibiotic that caused sunlight to mutate36 PITTMED

medicine. In Pittsburgh, he had the chance to work outsideof the hospital with Pittsburgh EMS as part of his hospitalrotations. “It was an incredible experience,” he says.Thomson was recently named director of emergency medicineat St. Joseph’s Hospital Health Center in Syracuse, N.Y.,where he still enjoys working with the local EMS providersas medical director for ambulance and emergency services.He also collaborates with fellow Pitt trainee Kevin Hutton(Emergency Medicine Resident ’90), CEO of Golden HourData Systems, developing software and communicationstools for air transport providers.Padmavati Garvey (MD ’92), a classical Indian dancer,has trained in the ancient Bharatanatyam style since herchildhood in Pittsburgh and now performs with a dancetroupe in New York. She and her daughter are eagerly learningthe Kuchipudi style. In her professional life, Garvey,whose father worked in Pitt’s pathology department, isan ob/gyn at the Westchester Medical Center of New YorkMedical College. Her research examines how economicfactors influence a woman’s decision to use or not to usecontraception. She also is studying the relationship betweenbreast-feeding and premenopausal breast cancer.As a child, Teresa Smith (MD ’97) admired the Pitt degreehanging over the desk of John Bono (MD ’48), who removedher tonsils. He was one of many Pitt doctors who impressedSmith with their intellect, compassion, and skill. Althoughshe had always been interested in medicine, Smith spent10 years teaching high school chemistry and physics, until,Members of the Class of 1996 and familygathered at Doc’s Place in Shadyside beforethis year’s Scope and Scalpel. From left:Karen Kreiling, Leila Kahwati, Richard Oh(with daughter, Elena), Anna Peris, MarshalPeris, James Jarvis, Elizabeth Woo, EricaJarvis, Nickie Kolovos, and Benedict Woorecall the glories of performances past.she says, “I realized it was time.” She took theMCATs, thinking that a bad score would showher that she should give up all thoughts of medicalschool. After doing well on the exam, shethen applied only to Pitt, sure that a rejectionletter would offer proof that she didn’t belong inmedicine. She is now one of around 150 neurointensivistsin the United States. She becamedirector of neurosurgical intensive care for theUniversity of Michigan Health System last year.Eileen Everly (MD ’99) is the new medicaldirector of the Reach Out and Read programat the Children’s Hospital of Philadelphia. Thenational nonprofit campaign provides childrenfrom birth to age 5 with a new, age-appropriatebook at each well-baby visit. Everly, who fell inlove with the program during her residency atthe University of Maryland, encourages parentsto spend time every day reading aloud to theirchildren, even as newborns. For bilingual families,the program provides books in other languages,including Korean, Spanish, French, andVietnamese. Although she arrived at Pitt intendingto become a neurosurgeon, Everly is now apediatrician. She says, “Kids are just the bestpeople. They’re full of joy and hope, and everyday at least one of them makes me laugh.”—Alicia Kopar, Jaclyn MaddenDNA—until Williams determined what was responsible and guided thepharmaceutical company to engineer it out—and an anti-estrogen drugthat induced liver tumors in rats, but not humans. “We have to havethe greatest assurance of safety before administering drugs to anyWilliams people,” he says sternly.Williams is especially proud of receiving the Enhancement of AnimalWelfare Award from the Society of Toxicology for developing testing systemsthat don’t use animals. The nutrient medium he developed for culturing livercells in vitro led to a pioneering way to assess chemical DNA damage and wasone of the many reasons the American Chemical Society named him a distinguishedscientist.In his consumer product studies, Williams has calmed fears about popularsubstances like tooth whitener and hair coloring. The bottom line for thoseproducts? “No harmful substances are released into the body,” he says.It’s nice to hear some things in the grocery store are safe.— Jennifer DionisioTHE WAY WE ARECLASS OF ’96During med school, the Class of ’96 used to gettogether at Doc’s Place in Shadyside for camaraderieand cheesy pizza. What better place togather before attending the Class of 2006’s productionof Scope and Scalpel and recall their own? Ten yearsbefore, they parodied A Chorus Line and themselves.They danced in lab coats and silver top hats, butinstead of singing, “One singular sensation, every littlestep he takes,” they sang “Done with confabulationand the new curriculum.”Nickie Kolovos (MD ’96) is credited with thechorus line idea. She’s currently assistant professorof pediatrics and medical director of the traumaunit in the pediatric ICU of Washington Universityin St. Louis. One Christmas Eve, a 6-year-old girlwith influenza myocarditis, a rare inflammation ofthe heart due to influenza infection, was rushed toKolovos’ unit. Her team performed CPR for twohours. Kolovos doubted her patient would live. Nowevery few months, she gets a friendly visit from herhealthy young patient and the child’s father.Kolovos says she enjoys working with childrenbecause their health issues are uncomplicatedby a history of life choices: “Everythingabout their physiology makes sense.”Marshal Peris (MD ’96, Res ’01, Fel’02), the class president who admits to stumblingthrough Scope and Scalpel choreography10 years ago, now lives in a place namedMount Kisco. But his New York plates read:BLKNGOLD, and he holds Steelers seasontickets. For Super Bowl XL, he traveled toDetroit with Louis Klieger (MD ’96, Res ’00),Walter Delgaudio (MD ’96), James Jarvis (MD’96, Res ’99), and Benny Woo (MD ’96, Res ’00) towatch the Steelers win the Lombardi Trophy.At Northern Westchester Hospital Center, Peris isthe only full-time orthopaedic spine surgeon. He treatsdegenerative conditions of the spine as well as traumaticinjuries. Peris says he is impressed that many ofhis classmates went on to pursue specialized training.One such colleague is Brian Pettiford (MD ’96,Res ’01, Fel ’03). His father and grandfather weremechanics well known in Tifton, Ga. Their handscould fix anything. After his maternal grandmotherdied from a heart attack, Pettiford was moved todevote the skilled hands he inherited to thoracicmedicine. He is now a Pitt clinical assistant professorof surgery, working primarily with lung afflictions.He attempts to uphold his soft-spoken grandmother’sgentleman ideal through his interactions with patientsand colleagues. — Alicia KoparFALL 2006 37

IN MEMORIAM’40sHERMAN BEARZYMD ’43BMARCH 18, 2006WILLIAM F. BAIRDMD ’45APRIL 15, 2006’50sJAMES L. HOOBLERMD ’55DEC. 5, 2005THOMAS E. CADMANMD ’56MARCH 15, 2006RICHARD DOBIESMD ’57MARCH 16, 2006GERARD HOGARTYJULY 14, 1935–APRIL 7, 2006Gerard Hogarty was a rare gem. With no MDor PhD degree, he was a self-taught psychiatricHogartyresearcher who had an enormous impact on theway we treat schizophrenia. The professor of psychiatry came to theUniversity of Pittsburgh in 1974 with a master’s degree in socialwork and a decade of experience in schizophrenia research.When Hogarty entered the field, schizophrenia treatment waslimited mostly to medication, because it had been demonstrated thatpsychoanalysis did not work, says his colleague, Rohan Ganguli, Pittprofessor of psychiatry. “Gerry showed that there was a powerful rolefor psychological treatments in improving the lives and the outcomesfor those with schizophrenia.” With colleagues at Pitt, Hogartydemonstrated that early intervention that involved and educatedthe patient’s family could reduce the chance of relapse and improveoutcome. “That has become absolutely standard treatment aroundthe world,” says Ganguli. —Chuck StaresinicDONALD LEONAUG. 19, 1932–JUNE 21, 2006’60sMELVIN KADENMD ’63APRIL 1, 2006’70sRANDALL KRAMERMD ’72MARCH 1, 2006’80sD. RICHARDSTRAUSBAUGHMD ’80MAY 13, 2006Donald Leon (Fel ’64) began and ended his medicalcareer at Georgetown University Hospital, but hisLeonyears there were bookends to a quarter century ofservice at the University of Pittsburgh. The noted cardiologist was amaster of the American College of Cardiology and former dean ofPitt’s School of Medicine.Leon arrived at Pitt in 1963 as a research fellow in cardiology. Fiveyears later, as an assistant professor, he was selected as one of the firstsix American Heart Association Teaching Scholars in Cardiology.“It was quite a feather in his cap,” notes James Shaver, a Pitt professorof cardiology. “He excelled in bedside teaching and lecturing.”Leon was dean of the school of medicine from 1979 to 1984. Hewas instrumental in the recruitment of transplant surgeon Thomas Starzlin 1981, oversaw the restructuring of the school’s basic science departments,and was one of the founders of Family House, a nonprofit thatassists and houses families traveling to Pittsburgh for lifesaving care.“It really made an impression, both on the city and on those coming,”says Shaver regarding Family House. “It helped to build theimage of Pitt that drastically changed in the 1990s as people camefrom all over the country and all over the world.” —CSBILL WALLACEFEB. 26, 1944–MAY 28, 2006Those who knew him say Bill Wallace changed Pitt’sSchool of Medicine forever and for the better in Wallacejust two years. Arriving as assistant dean of studentaffairs in 1979, Wallace became the school’s first dean of minorityaffairs before he left in 1981.“He rallied the medical students, became actively engaged in theadmissions process, met with faculty to emphasize the benefits ofdiversity, and began surveying all applicants,” said Jeannette South-Paul (MD ’79), Pitt’s Andrew W. Mathieson Professor and chair ofthe Department of Family Medicine. “His persistence, dedication, andfocus created a foundation for reaching out to minorities.”Wallace was a graduate of Howard University, New York MedicalCollege, and Harvard University, where he received a PhD inmicrobiology. His legacy at Pitt, says South-Paul, includes the talentedminority students that Pitt attracts annually. —CSEUGENE S. WIENERFEB. 28, 1940–JUNE 29, 2006Eugene S. Wiener was known as a tough taskmasterand star surgeon whose greatest passion was the Wienerhealth of children.The University of Pittsburgh School of Medicine professor ofsurgery and chief medical officer at Children’s Hospital of Pittsburghcame to Pitt in 1973 as a pediatric surgical resident, after serving as acommander and deputy chief health officer in Vietnam.Wiener guided multiple research projects directed at improvingpediatric cancer treatment, particularly in the area of surgical oncology.He published more than 85 articles in peer-reviewed journals andcontributed 18 book chapters.He was among the best in the surgical suite, colleagues note. HenriFord (Fel ’93), former chief of pediatric surgery at the University ofPittsburgh and current vice president and surgeon-in-chief at Children’sHospital Los Angeles, called him “the Michael Jordan of surgery.”Wiener helped Children’s implement a computerized physicianorder entry system designed to cut down on errors engendered by illegiblehandwriting and provide instant access to medical records.Children’s president and CEO Roger Oxendale said Wiener waspondering retirement but intended to remain involved with the hospitalin a development role as it moved to its new location in Lawrenceville.—Joe Miksch38 PITTMED

HOWARD RABINOWITZCOUNTRY STYLEBY JENNIFER DIONISIOSay a patient broke his leg. As a youngdoctor at Sacaton Indian Hospital,30 miles outside Phoenix on the Pimareservation, Howard Rabinowitz (MD ’71)would find himself loading the x-ray film,taking the picture, developing the film,casting the limb, running to the pharmacyfor pain medicine, counting out those pills,affixing the label, and passing the bottle tothe patient. There wasn’t anyone to delegateto, and he was one of only four doctorsserving a rural population of 10,000.“We basically did everything,” Rabinowitzrecalls 30 years later, sitting in his Philadelphiaoffice. The Thomas Jefferson University professorof family medicine spent two years atSacaton as a doc-of-all-trades before translatinghis knowledge of the issues surrounding smalltownhealth care into a position as director ofJefferson’s Physician Shortage Area Program.The program supports med students planningto work in underserved rural areas.“Most people think of Pennsylvania asPittsburgh and Philadelphia,” Rabinowitzsays, shaking a head covered in silver hair thatcontrasts with his youthful face. Although halfof the state’s doctors work in these two cities,almost 75 percent of the population lives inPennsylvania’s other 65 counties, he notes.Rabinowitz took a year sabbatical tofollow 10 of his graduates and documenttheir experiences in his book Caring for theCountry (Springer-Verlag, 2004). From directobservation in doctors’ offices and 150 hoursof taped interviews, Rabinowitz reveals aworkforce and patient population as diverseas that of any bustling metropolis. These doctors—manyare the only practitioners withina 20-mile radius—are certainly generalists,giving checkups, delivering babies, performingsurgery, and, yes, sometimes makinghouse calls.Rabinowitz was raised in Pittsburgh’sSquirrel Hill neighborhood and attendedNew Jersey’s Rutgers University. As a medstudent, Rabinowitz says, “I had never beenout of an urban area in my life.” At leastuntil his senior year at Pitt. At the urging ofa fellow student, Rabinowitz signed up inhis fourth year for professor of communitymedicine and pediatrics Ken Rogers’ electiveMEDICAL 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)HistorianCOURTESY RABINOWITZRabinowitz signs his book Caring for the Country for Senator Jay Rockefeller (left) of West Virginia.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 Directorthat took students on a nine-week rotation asresearchers in the Navajo Nation. “It soundedfascinating culturally, geographically, and alsomedically,” he says.He was so impressed by the experience, hereturned to work at Sacaton after his residency—manyof his fellow students also soughtpositions in Native American communities.Rabinowitz was driven to write Caringfor the Country by his concern that medicalstudents don’t realize that practicing in suchareas is even an option. What a shame, hesays now, considering that rural doctors heobserved seemed much happier than many heknows in urban areas. Far from consideringtheir extra responsibilities a burden, they takepride in being such integral members of thecommunity and enjoy raising their families inclose-knit towns. And despite the assumptionthat rural doctors work longer and get paidless, all those Rabinowitz interviewed felt afew extra hours in the office equal an urbandoctor’s commute time—and cost-of-livingdifferences assure financial security.Small-town living isn’t for everyone,Rabinowitz acknowledges. He can tell whichstudents will be successful in the program justby asking if their hobbies lean toward operaor fishing.But his own early experience in the NavajoNation was deeply satisfying. He’s sincefound that patients in small towns receivea kind of intimate care often lacking in bigcities like Philadelphia.“I wrote the book for students to get a senseof this,” he says.■M-200k Scaife HallUniversity of PittsburghPittsburgh, PA 15261tel 412-648-9090; fax 412-648-9500medalum@medschool.pitt.edu FALL 2006 39

LAST CALLTRANSPLANT TRANSPLANTSIn case you were wondering how influential Thomas Starzl hasbeen in the world of transplantation, have a look at this map.The dots mark where his first- and second-generation traineesrun or most recently ran programs.MICHAEL LOTENEROLEGEND• first generation• second generationDavid Imagawa, Irvine, Calif.PROGENITOR:Thomas Starzl, PittsburghFIRST-GENERATIONPROGENY PROGRAMDIRECTORS:Kareem Abu-Elmagd (Fel ’91),Pittsburgh, Pa.Mario Alessiani (Fel ’89), Pavia, ItalyGiovanni Ambrosino (Fel ’87), Vicenza, ItalyRonald Busuttil (Fel ’85),Los Angeles, Calif.Joseph Cofer (Fel ’89), Charleston, S.C.Waldo Concepcion (Fel ’89),Loma Linda, Calif.Frank Darras (Fel ’92), Stony Brook, N.Y.S. Forrest Dodson (Fel ’93), Chicago, Ill.Caren Eisenstein (Fel ’89),Fort Worth, Texas.Carlos Esquivel (Fel ’85), Palo Alto, Calif.Paulo Fontes (Fel ’91), Pittsburgh, Pa.John Fung (Fel ’86), Cleveland, OhioTimothy Gayowski (Fel ’92), Pittsburgh, Pa.Robert Goldstein (Fel ’88), Dallas, TexasFranklin Greif (Fel ’91), Tel Aviv, IsraelGlenn Halff (Fel ’89), San Antonio, TexasTodd Howard (Fel ’88), St. Louis, Mo.Zakiyah Kadry (Fel ’93), Hershey, Pa.Igal Kam (Fel ’85), Denver, Colo.Frederick Karrer (Fel ’86), Denver, Colo.Baburao Koneru (Fel ’87), Newark, N.J.Ignazio Marino (Fel ’92), Philadelphia, Pa.Maureen Martin (Fel ’91),Bakersfield, Calif.Jorge Maza (Fel ’90), Mexico City, MexicoHadar Merhav (Fel ’89), Tel Aviv, IsraelLuis Mieles (Fel ’86), Houston, TexasAkimasa Nakao (Fel ’90), Nagoya, JapanPaul Nakazato (Fel ’88), Tucson, Ariz.Mark Nelson (Fel ’89), Cumberland, Md.Hector Ramos (Fel ’91), Los Angeles, Calif.David Reich (Fel ’92), Philadelphia, Pa.Jorge Reyes (Fel ’89), Seattle, Wash.Kerri Robertson (Fel ’87), Durham, N.C.Mahmoud Sakr (Fel ’89), Ahmadi, KuwaitEduardo de Santibanes (Fel ’83),Buenos Aires, ArgentinaVelma Scantlebury (Fel ’88), Mobile, Ala.Robert Selby (Fel ’89), Los Angeles, Calif.Ron Shapiro (Fel ’88), Pittsburgh, Pa.Timothy Shaver (Fel ’88), Farmville, Va.Byers Shaw (Fel ’83), Omaha, Neb.Linda Sher (Fel ’88), Los Angeles, Calif.Rodney Taylor (Fel ’82), Burlington, Mass.Lewis Teperman (Fel ’88), New York, N.Y.Andreas Tzakis (Fel ’85), Miami, Fla.Ferdinand Ukah (Fel ’92), Mobile, Ala.Dorian Wilson (Fel ’88), Springfield, N.J.Youmin Wu (Fel ’93), Little Rock, Ark.Katsuhiko Yanaga (Fel ’89), Tokyo, JapanSECOND-GENERATIONPROGENY PROGRAMDIRECTORS:George Blessios (Fel ’98), Buffalo, N.Y.Rafael Botero, Houston, TexasAdel Bozorgzadeh (Fel ’99), Rochester, N.Y.J. Stevenson Bynon, Birmingham, Ala.Pradip Chakrabarti (Fel ’00), Allentown, Pa.Steven Colquhoun, Los Angeles, Calif.John Daller (Fel ’99), Rochester, N.Y.Cataldo Doria (Fel ’97), Philadelphia, Pa.Douglas Farmer, Los Angeles, Calif.Thomas Faust, Philadelphia, Pa.Ermenegildo Eldo Frezza (Fel ’01),Lubbock, TexasJonathan Fridell (Fel ’02), Indianapolis, Ind.Joseph Galati, Houston, TexasDavid Geller (Fel ’98), Pittsburgh, Pa.David Gerber (MD ’89, Fel ’98),Chapel Hill, N.C.John Goss, Houston, TexasHans Albin Gritsch (Fel ’94),Los Angeles, Calif.Frederick Grover, Denver, Colo.William Hecker (Fel ’97), Philadelphia, Pa.Sayed Ali Malek Hosseini (Fel ’92),Shiraz, IranNicolas Jabbour (Fel ’94), Los Angeles, Calif.Daniel Katz (Fel ’00), Iowa City, IowaAbrar Khan (Fel ’00), Burlington, Vt.M. Farouk Ali Khan (Fel ’95), Camden, N.J.Ajai Khanna (Fel ’95), San Diego, Calif.Milan Kinkhabwala, New York, N.Y.Alan Langnas, Omaha, Neb.James Lim (Fel ’96), New Brunswick, N.J.Jeffrey Lowell, St. Louis, Mo.Patrick Luke (Fel ’00), London, CanadaMario Magnone (Fel ’95), Mobile, Ala.James Markmann, Philadelphia, Pa.Luis Santiago Marsano-Obando,Louisville, Ky.George Mazariegos (Fel ’94), Pittsburgh, Pa.J. Michael Millis, Chicago, Ill.Ernesto Molmenti (Fel ’98), Tucson, Ariz.Kim Olthoff, Philadelphia, Pa.Thomas Peters, Jacksonville, Fla.Santosh Potdar (Fel ’01), Danville, Calif.Ruben Quiros, Houston, TexasCarlo Ramirez (Fel ’95), Manila, PhilippinesDinesh Ranjan, Lexington, Ky.K. Rajender Reddy, Philadelphia, Pa.Steven Rudich, Cincinnati, OhioAbraham Shaked, Philadelphia, Pa.Craig Smith (Fel ’96), Los Angeles, Calif.James Spivey, Atlanta, Ga.Debra Sudan, Omaha, Neb.Atsushi Sugitani (Fel ’97), Fukuoka, JapanNgoc Thai (MD ’97, Fel ’04), Pittsburgh, Pa.Phillip Thomas (Fel ’95), Bangalore, India—Compiled by Jaclyn Madden40 PITTMED

C A L E N D A ROF SPECIAL INTEREST TO ALUMNI AND FRIENDSUnless otherwise noted, for informationon an event contact the Medical AlumniAssociation: 1-877-MED-ALUMmedalum@medschool.pitt.edu.WHITE COAT CEREMONYAUGUST 133 p.m.Scaife Hall, Auditorium 6CLEVELAND HEALTHSCIENCES ALUMNIRECEPTIONSEPTEMBER 20Cleveland, OhioFor information:Pat Carver412-647-5307cpat@pitt.eduHOMECOMING WEEKENDOCTOBER 19 –22Pittsburgh v. RutgersSaturday, October 21For information:www.alumni.pitt.eduMUSGRAVE LECTURESHIPOCTOBER 275:30 p.m.Scaife Hall, Auditorium 5James W. May Jr., MD, SpeakerOCTOBER 2810 a.m.Scaife Hall, Auditorium 5Surgery Grand RoundsAAMC PITT RECEPTIONOCTOBER 296 p.m.AAMC Annual MeetingGrand Hyatt SeattleSeattle, Wash.For information:Office of the Vice Dean412-648-9000vicedeanstaff@medschool.pitt.eduWINTER ACADEMY SCHOOLSOF THE HEALTH SCIENCESFEBRUARY 2007Naples, Fla.To request an invitation:Pat Carver412-647-5307cpat@pitt.eduMEDICAL ALUMNIWEEKEND 2007MAY 18–20, 2007Reunion Classes:1947 19521957 19621967 19721977 19821987 19921997Upcoming health sciencesalumni receptions—October: Dallas, TexasNovember: Philadelphia, Pa.March 2007: Raleigh/Durham, N.C.May 2007: Erie, Pa.For information:Pat Carver412-647-5307cpat@pitt.eduTO FIND OUT WHAT ELSE IS HAPPENING AT THE MEDICAL SCHOOL, GO TO www.health.pitt.edu

WELL SUITEDWhen Pitt is the best fit for terrific applicants, don’t let concerns about costs squelch theirdreams. A planned gift to the School of Medicine can be directed toward scholarships orother meaningful projects to keep the best and brightest gracing the halls of Scaife. In themeantime, it can provide an annual income stream for you or a loved one. (If the School ofMedicine is already in your will and you haven’t let us know, please contact us so that wecan make sure your gift is used as you intend it to be.)FOR MORE INFORMATION: School of Medicine, University of Pittsburgh,Kathleen Helling, Medical Arts Bldg., Suite 400, 3708 Fifth Ave., Pittsburgh, PA 15213412-647-4220, hkathleen@pmhsf.orgLEFT TO RIGHT: C. 1963, ROZELL, EZELL, AND JEWELL PENDLETON, BROTHERS OF ROBERT HILL, PITT VICE CHANCELLOR FOR PUBLIC AFFAIRSUNIVERSITY OF PITTSBURGHSCHOOL OF MEDICINESUITE 401 SCAIFE HALLPITTSBURGH, PA 15261CHANGE SERVICE REQUESTED