WHAT MAKES GENIUS HAPPEN? - Pitt Med - University of Pittsburgh

UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE | WINTER 2011/12PITTMEDWHAT MAKES GENIUS HAPPEN?GEOMETRICAL DRAWINGS BY LEONARDO DA VINCI (1452–1519).

OVER THE TRANSOMOLDEST LIVING ALUMNUS?On page 40, in your last paragraph of the LastCall [“The Only School of Note,” Fall 2011], youmake a statement that Paul Caplan is the oldestliving alumnus. This may be so, but I mightchallenge that. My birthday is Oct. 14, 1913. (Ibelieve that a search of alumni records wouldlikely show that century-old members exist.)I am of the Class of 1937, and I’m 98. I wasa Pitt med school faculty member from 1938–1953 with the Department of PhysiologicalChemistry. Part of that time I served in WWII,and later I received a PhD in biochemistryfrom St. Louis University. I finally left Pitt byreturning to a career in the USAF in aerospacemedical research. I commanded three differentlaboratories.Incidentally, I found this issue of Pitt Medmost interesting, since I am old enough to havelived through much of the history and peopleyou reported on. I’m keeping my copy!Joseph Quashnock (MD ’37)San Antonio, TexasDr. Caplan’s birthday is Nov. 21, 1912.LANSING: BOOK WORTHYI am an alumnus of the University of PittsburghSchool of Medicine, Class of 1960.The book that I’ve just published, TheLansing Effect, is dedicated to Professor AlbertI. Lansing, who was chair of the Department ofAnatomy at the time I studied at the medicalschool. Lansing was well known internationallyfor his work in many areas, especially thestudy of the biology and physiology of aging(gerontology). [Simply put, the Lansing effecthypothesizes that the offspring of old parentstend to have shorter lifespans than the offspringof young parents.] Some of the topics that fascinatedLansing—and, because of my friendshipwith him, also fascinated me—are themes in thisnew book. They are quite relevant to current-dayissues of importance to the medical profession,scientifically and ethically.By the way, I enjoy the articles in Pitt Med.It is a first-class publication.Donald Malkoff (MD ’60)Centreville, Va.KEEPING UP WITHDR. HUMPHREYI have read and reread better than half of thearticles you have published in the magazine.Without hesitation, I can say it is one of themany magazines and journals that I look forwardto receiving. I have shown certain articles tofriends and colleagues who are truly impressedwith the overall quality.In regard to Dr. Tryphena Humphrey, theneuroanatomy teacher in the ’50s and ’60s:She was a small, white-haired, grandmotherlywoman. To be sure I was not exaggerating orhallucinating, I checked with a couple of classmates,who confirmed these impressions: Duringclass, she drew on the blackboard renderings ofthe brain and spinal cord, including the spinaltracts, ganglia, crossovers, etc. She ordinarily hadapproximately 10 colors of chalk with which shecould write and draw (using both hands) whilesimultaneously lecturing. It was impossible forthe 100 students to even hope to keep pace withher. All students came to class with a box of 10to 12 colored pencils to duplicate her drawings,which were phenomenal. Heaven forbid that alead in one of your pencils broke, as you wereS.O.L.! There were no textbooks of neuroanatomythat contained diagrams as detailed as hers.She was in the Department of Anatomy with Dr.Davenport Hooker and Dr. Jacob Priman, whowere also outstanding.I believe all in the class (except perhaps thosewho failed) loved Dr. Humphrey. She would bedeserving of recognition in one of your futureissues.Keep up the excellent work.Lawrence Gilford (MD ’59)Brookville, Pa.We gladly receive letters (which we mayedit for length, style, and clarity).Pitt Med400 Craig HallUniversity of PittsburghPittsburgh, PA 15260Phone: 412-624-4152Fax: 412-624-1021E-mail: medmag@pitt.eduhttp://pittmed.health.pitt.eduFor address corrections:Pitt Med Address CorrectionM-200K Scaife HallUniversity of PittsburghPittsburgh, PA 15261E-mail: medalum@medschool.pitt.eduRECENTMAGAZINE HONORS2011 IABC Golden TriangleAward of Excellence, Feature Writing(E. Vitone, “Mars and Venus Revisited”)2011 IABC Golden TriangleAward of Honor, Magazines2010 CASE Circle of ExcellenceGold, Periodical Staff Writing

PITTMEDUNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE MAGAZINE, WINTER 2011/12VOL. 13, ISSUE 4DEPARTMENTSOF NOTE 3Kensler cheered by China.Dr. Watson, we presume.Big showing in Small World.CONTRIBUTORSCLOSER 7A new liver and a big heart.INVESTIGATIONS 8Summer of science.Lasting vasculature.Asthma aggravators.98.6 DEGREES 32Thanks a million (dollars), Class of ’61.ATTENDINGATTENDING3333Oh,Oh,thetheplacesplacesyou’llyou’llgo,go,PittPittmeder!meder!ALUMNI NEWS 36Jan Smith—we knew you when.Tinnitus: filling the silence.Imagining a universal vaccine.(Shown here: a mathematicalLAST CALL 40depiction of a sound wave.)27If you livedLASThere, you’dCALLbe home40by now.If you lived here, you’d be home by now.A decade ago, ALLA KATSNELSON [“Genius!”] was pipetting her way to a PhD in neuroscienceat Oxford, when one day, quite out of nowhere, the experiment she’d been running for monthsstopped working—and never worked again. When she asked around, everyone kept telling her itcould be anything: a new bag of water bath, a changed filter on the water dispenser. Katsnelsontroubleshot every wild card she could think of, but still, no dice. “It was a massive method failurethat almost undid me,” she says. After completing her degree, she made a career change to sciencewriting. This was not because of the (still-yet-unsolved) mystery of her experiment’s doom;nonetheless, methods in science has become one of her favorite subjects. Katsnelson is a formernews editor for The Scientist and former reporter for Nature. These days, she’s a staff writer fora soon-to-be-launched multiple sclerosis–research site and a freelancer for such publications asScientific American and Nature Medicine.Illustrator STACY INNERST [“Pitt Med Was Here”] spent 17 years on staff at the PittsburghPost-Gazette. His style, he says, is “sort of painterly and primitive.” The New York Times, PBS, andchildren’s books are some of the places you might see Innerst’s illustrations. For Pitt Med, hereimagined the world itself: “I liked the chance to depict a map of the world in an artful way; torepresent something people are so academically familiar with and take it in a different direction,”Innerst says. He gets a particular kick from his children’s book work. His M is for Music, withauthor Kathleen Krull, won a Gold Medal from the Parents’ Choice Book Awards. His work wasfeatured at the Art Institute of Chicago’s 2011 Picture Book Gallery exhibition, Artful Alphabets.COVERRGeometrical drawings about transformation from curved to rectilinear surfaces and vice versafrom Codex Atlanticus, Leonardo da Vinci (1452-1519). (Cover: Getty, 2011.)FEATURESGenius! 12Edison said that genius is “1 percent inspiration, 99 percent perspiration.”But where does inspiration come from? Stories and perspectives fromfolks who might know, including Pitt’s newly anointed MacArthur fellow,Elodie Ghedin, and scientific stars like J. Craig Venter.COVER STORY BY ALLA KATSNELSON, ERICA LLOYD,JOE MIKSCH, AND SHARON TREGASKISThe Natural 22For his 12th birthday, Jeremy Berg received a copy of Linus Pauling’sThe Architecture of Molecules. Since then, he has helped scientists understandhow DNA binds with proteins, become a department chair at 32, anddirected an NIH institute. What’s next? The University of Pittsburgh.BY REID R. FRAZIERStatic 27Thanos Tzounopoulos has learned that tinnitus is a betrayal of ourbiology that’s rooted in the very strengths that have contributed tohumanity’s success: memory, learning, and adaptability.BY ELAINE VITONE

DEAN’S MESSAGEPITTMEDPUBLISHERArthur S. Levine, MDEDITOR IN CHIEFErica LloydART DIRECTORElena Gialamas CerriSENIOR EDITORJoe MikschASSOCIATE EDITORElaine VitoneCONTRIBUTING EDITORChuck StaresinicPRODUCTION MANAGERChuck DinsmoreSTAFF CONTRIBUTORSMaureen Passmore, Jessica TitlerOBITUARIES CONTRIBUTORMacy Levine, MD ’43CIRCULATION MANAGERCrystal KubicEDITORIAL ADVISORSJeremy Berg, PhDMichelle Broido, PhDNancy Davidson, MDPaula Davis, MASusan Dunmire, MD ’85, Res ’88Joan Harvey, MDSteven Kanter, MDDavid Kupfer, MDJoan Lakoski, PhDMargaret Larkins-Pettigrew, MD ’94, Res ’98David Lewis, MDMargaret C. McDonald, PhD, MFAG. Sarah Napoe, Class ’12Laura Niedernhofer, MD, PhDDavid Perlmutter, MDSteven Shapiro, MDPeter Strick, PhDBennett Van Houten, PhDSimon Watkins, PhDMarshall Webster, MD, Res ’70Julius Youngner, ScDOFFICE OF PUBLIC AFFAIRSRobert HillJohn D. Harvith, JDAnd no, we don’t know where it willlead. We just know there’s somethingmuch bigger than any of us here.—Steve JobsWe live in an era of spectacular advances inmedical research. Driven by almost unimaginablypowerful technology, we gain further insight intohuman biology and illness almost by the hour;the momentum isn’t slowing. A family of cellularmolecules known as microRNAs (miRNA), not even known until the mid-1990s, is ableto affect the ultimate expression of many of our genes. Just in the past few months, we havelearned that these molecules can be transferred between our tissues and organs and that we caneven absorb them by eating miRNA-containing plants. The human benefit may be profound:For example, certain miRNAs can increase our high-density lipoproteins (HDL) and lower ourlow-density lipoproteins (LDL), thereby potentially reducing the risk of cardiovascular disease.Although the pharmaceutical pipeline is thought to be “dry,” with few if any new paradigmshiftingdrugs emerging, the fact is that we sit on the brink of extraordinary discoveries based onour rapidly emerging knowledge of druggable cellular targets, the use of molecules like miRNAsas “drugs,” the new ability to grow human cells on chips for drug effect and toxicity studies, andthe power of computational and systems biology to take us past our knowledge of an individualpatient’s genome to a rich understanding of how that person’s genome is ultimately expressed ina single cell and at an instant in time.Thus, there is no question that great science today is leading to great medicine tomorrow—fasterthan ever. Great science is also great business. Every $1 million in research fundingis estimated to generate 36 jobs—directly and indirectly. In fiscal year 2010, the University ofPittsburgh, driven by the medical school, received $800 million in research support. That hasyielded almost 30,000 jobs! A November 2011 economic analysis estimates that federal- andstate-funded research received by U.S. medical schools and their associated teaching hospitalsadded close to $45 billion to our economy in 2009. Moreover, the $4 billion invested sofar in mapping the human genome has yielded an estimated $560 billion in new drugs andother health-related research advances—quite a return! The NIH estimates that the gains inlife expectancy in this country since 1970 are worth some $3.2 trillion annually in enhancedproductivity. Antiretroviral therapies have turned AIDS from a fatal to a chronic condition,enabling people diagnosed in their 20s to live and work until a normal retirement age. Cancerincidence is now falling at the rate of 1 percent per year, with each percent decline savingapproximately $500 billion in otherwise lost productivity. But I’ve described only the economicimpact that research has had in the past, not what we can anticipate for the future. The longawaitedera of “personalized medicine” will be part of routine clinical practice within the nextdecade; therapies based on a person’s specific genetic profile are already used routinely for somediseases. Here, in collaboration with UPMC, we are launching a new Institute for PersonalizedMedicine to apply our own research to improving disease prevention and the treatment of ourpatients. Forgive the idiom, but … is great science great medicine and great business—or what?JOSHUA FRANZOSPitt Med is published by the Office of the Dean and Senior ViceChancellor for the Health Sciences in cooperation with the alumniand public affairs offices. It is produced quarterly for alumni, students,staff, faculty, and friends of the School of Medicine. PR 6718The University of Pittsburgh is an affirmative action, equalopportunity institution. © 2011, University of PittsburghArthur S. Levine, MDSenior Vice Chancellor for the Health SciencesDean, School of Medicine2 PITTMED

OF NOTEDevoted to noteworthy happeningsat the medical schoolGETTING CURES TO THE CLINICILLUSTRATION ROB KELLY (BASED ON PHOTO COURTESY T. KENSLER)The Clinical and Translational Science Institute (CTSI) at the Universityof Pittsburgh was founded on the principle that more needed to bedone to speed up the process of transforming achievements made inthe laboratory into therapies used in the clinic.The National Institutes of Health seems to think that CTSI is doinga fine job, if one can draw inferences from a recent five-year, $67.3million grant. Pitt’s CTSI is one of 10 such institutes nationwide tohave its funding renewed in 2011. Since its founding in 2006 with an$83.5 million grant, CTSI (a collaboration between Pitt, UPMC, CarnegieMellon University, and the Urban League of Greater Pittsburgh) hashad success in creating computer software to improve the diagnosis ofmelanoma, made advances in the study of sleep disorders, and fundedresearch into the efficacy of low-cost prescription drug programs—toname just a few of the thousands ofstudies CTSI has supported.—Joe MikschFLASHBACKOn Jan. 14, 1931, the Associated Press reported,“It all started when somebody telephoned that‘two wild men’ were running loose on the campus.”A wagonload of Oakland police officers was dispatched,capturing Myrlen Morgan and Thomas Wilkins, certainthat the two were insane. Not long after, police releasedthe men, quite certain of their sanity! “The whole thingwas explained by a member of the faculty later. [Foran experiment on respiration,] students Myrlen andThomas were asked to run about the campus todemonstrate physical exertion.”Kensler receives theFriendship Award from VicePremier Zhang DejiangKensler Lauded AbroadThomas Kensler, a PhD professor of pharmacology and chemical biologyin the University of Pittsburgh School of Medicine, recently earned theNational Friendship Award from the People’s Republic of China. Accordingto China’s State Administration of Foreign Experts Affairs, the honor isthe country’s highest given to “foreign experts for outstanding contributionsto the country’s economic and social progress.”Kensler’s research centers on trying to understand how aflatoxins, carcinogensproduced by fungi that commonly grow in many dietary staples,contribute to the high incidence of liver cancer in the country’s population.He is also testing ways to detoxify our bodies of the carcinogen. Liver canceris among the three deadliest cancers worldwide. In some regions ofChina, one in 10 people dies from the disease.On Sept. 30, on the eve of the National Day of China, Kensler joinedother public health advocates, economists, and manufacturers as theywere honored in the Great Hall of the People in Beijing.“I have made the investment of my time and my energy,” saysKensler, “and the payback is great friendships. I’m always happy to goto my second home.” —Jessica TitlerWINTER 2011⁄12 3

A&Q with Aaron Baum on Finance and HealthWith a bachelor’s degree in mathematics from the University of Chicago, Aaron Baum (Class of’15) worked as an equities trader before entering the University of Pittsburgh School of Medicine’sClinical Scientist Training Program (CSTP). After his first year, Baum took a leave of absence tospend nine months in Haiti. There, he attempted to improve health care access for rural Haitianwomen and their families by working with Fonkoze, a microfinance bank. Now, he is taking anotherleave from med school to work toward a PhD in sustainable development at Columbia University.How a bank improves access to health careWhat we were doing was capitalizing on existing infrastructure. The way Fonkoze works is through anetwork. ... Most of the action, as far as the loans, takes place in the village centers where Fonkozeemployees distribute loans and get repayments. The village centers are where women congregatetwice monthly in an organized fashion, so you can use that opportunity to provide other services.We trained one client in each center to be able to identify malnourished children using a color-codedupper-arm circumference strip, and then we partnered with Partners in Health to provide care forthose children. That was the first project I started doing.We’re piloting a minipharmacy as a social business model where one client per village is trainedto distribute essential health commodities (such as oral rehydration solutions, deworming pills, andvitamins) for a small profit. Fonkoze also provides micro-insurance for catastrophe and will soonprovide it for cholera. So you can level off your risk as a Fonkoze client.What a degree in sustainable development offers[It’s] essentially an economics PhD plus one in natural science. It’s great if you are interested inhealth systems, which by default is a cross-sectoral issue.What he’ll be doing 10 years from nowI don’t know. Whatever I end up doing, I hope it will be related to community health systems andwill bridge implementation and research. I hope that I have clinical training, but I also hope there isresearch involved. I also want to be building something concrete.His question for usWhat are your ideas for starting financially viable community health programs via microfinance orother existing rural infrastructures? —Interview by Nick KepplerTIM GROENNext GenerationEarning a Doris Duke Clinical ResearchFellowship is a feather in the cap of ayoung physician-scientist. Rachel Orler(Class of ’13), a 2010–11 Duke fellow (one of eightfrom the school that academic year), made themost of her time away from the classroom. Lastfall, Reid was the first author on an Archivesof Internal Medicine paper titled “AssociationsBetween Physician Characteristics and Quality ofCare.” (The research, done with Ateev Mehrotra,assistant professor of medicine at Pitt as well asa policy researcher at RAND Corp., began as herscholarly research project.) As a Doris Duke fellow,Reid also researched the possible impactsof retail clinic visits on primary care medicine.Oh, and during her Doris Duke year, she earnedan MS in clinical research at Pitt. She’s spendingthis academic year at the Center for Medicare andMedicaid Innovation in Baltimore, Md., workingon ways to improve health care while loweringcosts. Next? “I’m thinking I’ll do an internalmedicine residency and then probably a generalmedicine fellowship. And after that, I’ll aim to bea physician-researcher doing health policy work.”Pitt med boasts nine new Doris Duke fellowsfor the 2011–12 academic year. Gillian Harrison isstudying the safety and efficacy of modified stromalcells in patients with stable ischemic stroke.Ryan Li is looking to define predictors of osteoarthritisafter ACL reconstruction. Rachael Maciaszis researching palliative care communicationtechniques for cancer patients. Brian Nolan isevaluating tools used to assess response to antiinflammatorytherapy in patients with rheumatoidarthritis. Michael Schowalter is undertakingthe proteomic analysis of pure- and mixed-typedesmoplastic melanoma, a rare metastatic skincancer. Ben Sprague is investigating noninvasivecardiovascular imaging. Ryan Stephenson seeksto understand the role of Toll-like receptors—proteinsthat play a key role in the innate immunesystem—in head and neck cancer. Lisa Tsengis evaluating the relationship between weightchange and physical function at the advent ofmenopause. And Jacky Yeung is endeavoring tosort out the role of molecular defects related tothe rare, and often fatal, brain cancer glioblastoma.—JM4 PITTMED

Dr. Watson,We PresumeAfter about five years of labor, the brainiacs atIBM made a very smart machine called Watson.It understands English (using software to extractmeaning from language) and kicks tail at Jeopardy!In early October, Dan Cerutti, IBM vice presidentfor Watson commercialization, and Steven Shapiro,former chair of medicine at Pitt and current chiefmedical and scientific officer for UPMC, met atScience2011 to talk about how Watson could be ofservice to medicine.Cerutti and Shapiro say that Watson will befed just about every scrap of information availableto the medical profession and use its speed andunique ability to derive likely answers to complexquestions. Watson is expected to be of use indiagnostics and as a way for patients and doctorsto work together before they even meet. UPMC’sTechnology Development Center is in negotiationswith IBM to help turn Watson the Jeopardy! champinto Watson, MD. Stay tuned. —JMReilly New Chair of MedicineJohn Reilly Jr., an MD, is now the Jack D. MyersProfessor and Chair of the Department of Medicineat the University of Pittsburgh, replacing StevenShapiro, who recently became UPMC’s chiefmedical and scientific officer. He wasrecruited to Pitt by Shapiro in 2008 tobecome the department’s vice chair ofclinical affairs; the two physicians hadworked together in Boston.Reilly Reilly is known for his studies on thegenetic and environmental factors associatedwith chronic obstructive pulmonary disease (COPD) and therole of alveolar macrophage enzymes in emphysema, COPD,and lung cancer.“I think medicine is going to change a great deal over thenext decade,” says Reilly. “What we need to focus on is workingwith the health care system to put tools in the hands ofclinicians so they can measure the kind of care they’re providingand can improve systems for delivering care.”On the research front, Reilly says, “We have a lot ofscientific talent here, and we need to take full advantage ofthe patient population that we have through UPMC. Beingable to access that clinical data to feed scientific researchmakes us the envy of most academic department chairsacross the country.” —JMCLASS OF 2015 CHEAT SHEETWe thought you’d like to meet a few of the med school’s new students:Michael Burrow learned cued language, a type of phonemic signedlanguage, so that he could communicate with his two sisters who are deaf.He later became a cued-language teacher and a certified cued-languagetransliterator. The 24-year-old entered the University of Utah after takingtwo years off for a mission trip to Thailand.Lauren Zammerilla graduated from the University of Pittsburgh in threeyears but made the most of her time while she was here. The cheerleaderand Phi Beta Kappa member was most proud of her sorority’s fundraisingefforts ($10 million nationally) for St. Jude Children’s Research Hospital.Alexis Chidi entered Pitt’s premed guaranteed admissions program atjust 16 years old. Since graduating in 2009, she has earned a Master ofPublic Health degree from Johns Hopkins University, where she was one ofa handful of students selected for the Global Health Field Research Award.The award allowed her to travel to Zambia to test the efficacy of using oralfluid samples to monitor immunity to malaria.Before coming to Pitt, Air Force Academy graduate John Jochum servedin the Air Force for 12 years as an F15-C Eagle pilot. The reason for thecareer change is the same one that first led him to the military: “It’s veryrewarding to wake up every day knowing that my hard work will be focusedon serving others,” he says. —Alexis WnukCATHERINE LAZURE4 PITTMED WINTER 2011⁄12 5

“BLADE OF GRASS,” COURTESY NIKON SMALL WORLD(VERY TINY)LEAVESOF GRASSThis photo earned Donna BeerStolz second prize in NikonInternational’s Small WorldCompetition. Taken through aconfocal microscope, this halfmillimeterof grass (magnified200 times) naturally fluoresces,showing off its blue trichomesand the green and red cells of theblade. How the image came to beis a somewhat convoluted story:Stolz, a PhD, is associate directorof the Center for Biologic Imagingand associate professor of cellbiology and physiology at theUniversity of Pittsburgh. She metNorth Side artist Diane Samuelsat a bar mitzvah. Samuels wasworking on a project mappingSampsonia Way, an effort thatincluded sampling and preservingthe alley’s flora. After talkingwith the artist, Stolz decided toput a bit of the grass under the’scope. And, “Wow!” (AnotherStolz image won 19th place, andthe entry of her Pitt colleague,Jonathan Franks, was named an“image of distinction.”) —JMConnamacher in Hall of HeroesRobert Connamacher, whose teaching efforts extend from an inner-cityelementary charter school to Pitt’s School of Medicine, has been inductedinto the Student National Medical Association’s Hall of Heroes. The organization,formed to assist medical students of color, bestowed the honoron Connamacher at its annual conference in Indianapolis last April. TheSNMA established the Hall just two years ago and has inducted only afew individuals thus far.“I’m sort of a pipeline by myself,” says Connamacher, a clinicalassociate professor of family medicine at Pitt who earned his PhD inpharmacology from George Washington University in 1966, of his effortsacross age brackets. The prof teaches a science program in the UrbanLeague of Greater Pittsburgh Charter School in East Liberty. There, amongother things, he orders students in grades one through five to run aroundthe other in configurations that model the parts of atoms. He also is theadvisor for Pitt’s Medical Explorers, a weekly program sponsored by themed school that gathers for advanced study high school students with aninterest in medicine. (Connamacher says they look at autopsies: “There isalways a gasp when we pull on a ligament and a finger moves.”) In addition,he teaches summer classes for premed undergrads at Pitt, as well ascourses at the School of Medicine. He has shepherded thousands of youngpeople in his 45 years of running such programs in Pittsburgh.Connamacher says he’s honored to be inducted into the Hall of Heroesbut adds that the “greatest reward for me is the number of students whomay not necessarily go on to medicine but find some direction throughthese classes.” —NK6 PITTMED

CLOSERWHILE WAITINGBarb Cozic (shown left) was having some liver trouble. In the morning ofNov. 1, she found out that “trouble” had developed into cancer. Later thatday, she and her niece Bree Cooper had a seat in the waiting room of theFrank Sarris Outpatient Clinic at the Thomas E. Starzl TransplantationInstitute, where Cozic was to be assessed for a new liver.A few minutes later, Robert “Bo” Garritano (right) and his wife, Joyce,strode into the room. They had been there before. Many times. On Oct.9, 2007, Garritano, at age 63—having been diagnosed with liver cancermonths before—underwent a liver transplant of his own. For the past coupleof years, the Garritanos have volunteered at the Starzl Institute, helpingothers know what to expect before and after transplantation.Bo Garritano introduced himself to the dozen or so in the waiting roomand then asked Cozic and Cooper where they were from. “Chester, WestVirginia,” they said. “West-by-God Virginia!” he boomed in response. Thevoluble Garritano told his story and listened to theirs. “I don’t even feelsick,” Cozic said to Garritano, “I said to myself, What am I doing here?”He replied, “What you have is a compensating liver. When you feel thisgood, you don’t know if you want a transplant. I felt so strong that I wasriding my bicycle in the city the day I got mine.”Garritano then wished Cozic and Cooper luck, counseled patience andresilience, and moved across the room to another waiting patient.“So,” Garritano said, “where are you from?” —Joe Miksch—Photograph by Martha RialWINTER W 2011⁄12 75

INVESTIGATIONSExplorations and revelations taking place in the medical school8 PITTMEDUPCI Summer Academy scholars take a break under the Roberto Clemente Bridgeduring a bicycling trip. FROM LEFT: Natalie Nash, Matt Miklasevich, Sam Rest (gettinghorizontal—“planking” in Internet fad-speak), Ishan Chatterjee (crouching behind),Andrew Shin, and program mentor William Buchser.

SMART FUNIN THE SUMMERTIMEHIGH SCHOOLERS SHINE IN CANCER ACADEMYBY MARC MELADA AND ELAINE VITONECOURTESY UPCI SUMMER ACADEMYOn a mid-July morning in 2011,Dilafruz Khakimova wakesup at 5 for her hour-anda-halfcommute on the 67bus from Monroeville toShadyside. It’s a typical workday in a laboratoryat the Hillman Cancer Center—youknow, interrogating DNA-replication forkprogression and the stability of DNA-repaircomplexes in human cells.Not too shabby for a 17-year-old, right?Khakimova is one of 25 high school studentsparticipating in the third-annual University ofPittsburgh Cancer Institute (UPCI) SummerAcademy. The program was started in 2009 topromote careers in cancer care and research torising juniors and seniors from both the localarea and beyond (students also come fromMaryland, Michigan, Indiana, Texas, NewJersey, and California). The students, referredto as scholars, pair up with a mentor researcherat the UPMC Hillman Cancer Center, Pitt’sDepartment of Biomedical Informatics, Pitt’sDepartment of Computational and SystemsBiology, or the Magee Womens ResearchInstitute. Each scholar completes a researchproject during the eight-week program.Khakimova arrives at her project site, thelab of Chris Bakkenist, Pitt assistant professorof radiation oncology, and opens an incubatorfilled with petri dishes containing lung cancercells. With the articulation and enthusiasm ofa grad student, she explains their hypothesis:The DNA-repair pathways known as ATMand ATR have a functional relationship andwork in tandem. If the hypothesis is right, thepopular cancer drug gemcitabine, which targetsATR to stall cancer-cell replication, couldbe made even more effective, she says.There’s a lot to do: tending to four differentcell lines; collecting the cells with a centrifugeand dividing them when they get too crowded;treating the cells with various pathway inhibitorsand examining cellular proteins to makesure those inhibitors are working; and, finally,determining whether the inhibitors kill thecancer cells.“The thing I’ve learned about lab work isthat it’s different every day,” Khakimova says.Today, she’s conducting a western blot, probingfor protein expression in lung cancer cellsby running them through the shaker (the pinkand-whitecontraption known around the labas “the belly dancer”).Lazy days of summer? “Seems like theynever existed,” says Khakimova. But shewouldn’t have it any other way. This is science.This is what she loves. Besides, it takes somedoing to outsmart oncogenesis. “My PI alwayssays, ‘Remember, Dela, we want to kill thecancer cells without damaging the other cells.’”In addition to her experimental research,throughout the Summer Academy program,Khakimova’s days are filled with traditionalclasses as well as field trips (to the NationalCancer Institute in Bethesda, Md., for example)and events like crab night at programdirector/instructor Michael Lotze’s home inShadyside. One of Khakimova’s favorite experienceswas donning scrubs and observingbypass surgery. “It was different than I imagined.They played happy music and werelaughing in the operating room.”The scholars are issued security passes.They’re given the same intellectual freedomand expected to show the same level of maturityas any med student or MD. Their mentorsprovide ideas to start with, but, “[Thescholars] make the projects work,” says Lotze.He adds that these responsibilities inspire thescholars to work hard, be imaginative, andtake on meaningful tasks.Lotze’s own Summer Academy mentee(from 2010 and 2011), Ishan Chatterjee,hopes to study at MIT and Pitt med. At theIntel International Science and EngineeringFair in Los Angeles last spring, he presentedpart of the project he started with Lotze, andhe placed second in cellular and molecularbiology. Natalie Nash, a fellow SummerAcademy scholar, also attended the event.Before the summer, Khakimova hadbeen thinking about going to med school tobecome a gastroenterologist. She knows nowthat she wants to work directly with patients.“My mom says I make connections with people,”she says. But lately Khakimova has beenthinking it would be fun to be a researcher,too. “They’re the ones coming up with allthese treatments,” she says.In its first three years, the academy classhas already grown from five students toalmost 30. Many of the scholars are fromeconomically disadvantaged backgrounds.The program is one of the med school’s severalmentoring programs for high school andundergraduate students. (It begins acceptingapplications in January.)For most 17-year-olds, achieving a leftwardshift on an optical-density graph isnot the highlight of the summer. But asKhakimova makes her way around the lab,it’s clear that there is no other place she wouldrather be.WINTER 2011⁄12 9

STRONGERHEARTSMOLECULE GOES THE DISTANCETO REGROW BLOOD VESSELSBY DANA YATESAheart attack is a trauma thatthe body never forgets. In fact,even after an arterial blockagehas been cleared, patients are still at risk ofheart failure down the road. But Yadong Wanghas developed a method that may one day helppeople heal from heart attacks once and for all.Wang is a PhD associate professor of surgeryin the University of Pittsburgh Schoolof Medicine and of bioengineering in Pitt’sSwanson School of Engineering. He is alsoon the faculty of Pitt and UPMC’s McGowanInstitute for Regenerative Medicine.“The body is able to heal itself in manyways. Just look at broken bones,” Wang says.“But when it comes to the heart, the body’snatural reaction isn’t enough.”Specifically, Wang is interested in heartdisease, the leading cause of death worldwide.Caused by a buildup of plaque in the arteries,coronary artery disease can slow down or stopblood flow to the heart. Once a heart attackoccurs, there’s no looking back. Dead muscleis replaced by stiff scar tissue, and the body’shealing process actually causes adverse changesin the heart’s shape, size, and function.This process, called pathological remodelling,involves thinning of the damaged ventricularwall, weakening and over-dilation ofthe ventricles, and enlargement of the heart.Taken together, these changes can lead to congestiveheart failure.That said, Wang is focused on reducingscarring and disrupting the downward spiralof remodelling by spurring the development ofnew blood vessels. And his weapon of choicein the fight against heart disease? A substancecalled growth factor.The body makes use of several growthfactors, each targeting various areas and handlingdifferent functions, including cell differentiationand cell migration. In light of thispotency, growth factor is strictly controlled bythe body, which releases the substance onlywhen absolutely necessary.“It’s an efficient system,” says Wang. It’s alsoa difficult one to manipulate. Previous researchhas shown that injections of growth factor areunproductive; the body destroys the substancetoo quickly for it to take proper effect.Wang wanted to buy growth factor moretime to do its job. So, with his research team,he explored how to control the release ofgrowth factor, bundling and delivering it in away that enabled the body to harness and usethe substance efficiently. The solution: Bonda molecule called heparin to the growth factor.As one of the molecules that binds growthfactor to its receptor on a cell’s surface, heparinmay stabilize growth factor and increaseits activity.After converting the resulting water-solublecompound into a coacervate—a collectionof oil droplets—the researchers injectedfibroblast growth factor-2 under the skin oflaboratory mice. In so doing, the Pitt team ofbioengineers and stem cell researchers—whichincludes Hunghao Chu, Jin Gao, WilliamChen, and Johnny Huard—became the firstAttempts to fortify damaged blood vesselswith growth factor have turned out vasculaturethat quickly breaks down—until a Pittteam concocted a unique compound (inset),which stimulated blood vessel growth inmice. background: The vessels held strongafter a month.to use a coacervate for the controlled deliveryof growth factor.Their findings, which were published inthe Aug. 1 issue of Proceedings of the NationalAcademy of Sciences, were encouraging. Thecompound led to the extensive formation ofnew blood vessels—ones that were robustand resembled arterioles, the small but criticalpathways that connect arteries to capillaries.In addition, the new blood vessels were longlasting.After just one injection of the growthfactor compound, the new structures were stillintact at least a month later.The coacervate is not viscous, so it can beinjected into the heart using a needle as thin asa strand of hair. The procedure, which couldbe performed immediately after a heart attackor even a few days later, would be much lessinvasive than open-heart surgery.The experimental treatment still must passmuster in clinical trials and be commercializedbefore it finds its way to patients. In the meantime,Wang is excited about the potential:“We are using nature to help people regenerateand recover,” he says.COURTESY HUNGHAO CHU10 PITTMED

People with severe asthma havehigher levels of 15LO1 enzyme(yellow). Top and bottom imagesshow cells of healthy and severelyasthmatic lungs, respectively.ASTHMAAGGRAVATORSFINDINGS THAT MAY HELPTHE MOST SERIOUS CASESBY MELINDA WENNER MOYERCOURTESY JINMING ZHAOWhen people with asthmasuffer an attack, the musclesaround their airwaystighten and their lungs fill with thick, stickymucus. More than anything else, it is thismucus that makes it impossible for them tocatch their breath. “The generation of mucusis considered to be one of the most importantpathological changes in asthma,” says Pitt professorof medicine Sally Wenzel, director of theUniversity of Pittsburgh Asthma Institute atUPMC. This is what led her to piece togetherthe details of a key signaling pathway that activatesmucus production—a pathway that shehopes to dial down so that one day people withsevere forms of asthma, an inflammatory lungcondition that causes 1.6 million emergencyroom visits annually in the United States, canbreathe more easily.Some asthmatics can effectively manage theirsymptoms using existing treatments like corticosteroidinhalers. But a small subset cannot,and research suggests that these patients havea unique biological signature characterized byimmune cells that overproduce inflammatoryproteins. One inflammatory protein in particular,interleukin-13 (IL-13), has interested Wenzelin part because it is known to play a role inmucus production. In 2010, she and colleaguesat a handful of institutions assessed the efficacyof an injected inhibitor of this protein on 243asthma patients, but they were disappointed todiscover that it did not significantly help.Part of the problem with blocking thisinflammatory protein is that “the levels thatyou can find in humans are infinitesimallysmall,” Wenzel says—it’s difficult to inhibitsomething that is only present in the body intiny amounts. Might it be possible, Wenzelwondered, to control mucus production differently,perhaps by targeting mucus-stimulatingmolecules downstream of this inflammatoryprotein? Wenzel knew of earlier studies suggestingthat the protein activated an enzymecalled 15-lipoxygenase 1 (15LO1) and itsbreakdown product, both of which are presentat higher levels in the lung cells of those withsevere asthma than in those of healthy people.She also knew that the inflammatory proteinturned on an enzyme called extracellular signal-regulatedkinase (ERK), which is rampedup more in asthma lung cells, as well. Wenzelwondered whether 15LO1 or its productmight somehow help to turn on the kinase andthereby control mucus production in asthma.To find out, she exposed lung cells takenfrom 65 asthma patients to the inflammatoryprotein. Levels of active kinase spiked withinminutes. But when she exposed the cells to theinflammatory protein for a week—and thenremoved the immune chemical and added itbriefly again—kinase levels were far higher.This finding suggested to her that perhaps theinflammatory protein stimulates the kinaseboth directly and indirectly, recruiting otherproteins that, over time, take over the activatingjob. Suspecting that 15LO1 or its productmight be one of these recruited proteins,Wenzel performed the same experiment whileinhibiting the production of 15LO1 to seewhat would happen. This time, the kinase wasactivated in much smaller amounts, whichsuggested that 15LO1 or its product plays animportant role in stimulating it.Wenzel believes that the inflammatory proteinturns on 15LO1 and then that 15LO1 orits product initiates a feedback loop that causessustained kinase activation (and ultimatelymucus production). She published her findingsin August in Proceedings of the NationalAcademy of Sciences. Ultimately, it may be that“some of these downstream pathways are goingto be more important than IL-13 itself” whenit comes to making mucus, she says.So how exactly does 15LO1 or its productactivate the kinase? The kinase gets turnedon when its activator molecule breaks awayfrom its natural inhibitor. In additional experiments,Wenzel showed that both 15LO1 andits product bind to this inhibitor and pull itaway from its activator, allowing the kinase toget turned on.Ultimately, Wenzel hopes to find ways toinhibit the activity of 15LO1 or its product (orboth) in order to slow mucus production andease asthma symptoms in people who don’thave other viable treatment options.“That is definitely, absolutely our goal,”she says.WINTER 2011⁄12 11

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COVER STORYCASE STUDIES:HOW TO DO MEANINGFUL AND INSPIRED WORKGENIUS!GEOMETRICAL DRAWINGS ABOUT TRANSFORMATION FROM CURVED TO RECTILINEAR SURFACES AND VICE VERSA, FROM CODEX ATLANTICUS, LEONARDO DA VINCI (1452–1519). © VENERANDA BIBLIOTECA.This September, ElodieGhedin received aMacArthur fellowship, theso-called genius award.What better occasion todelve into the nature ofinspiration?Elodie Ghedin, assistant professor of computational systemsbiology and member of the Center for Vaccine Research at theUniversity of Pittsburgh, runs a pretty small shop. The wayshe sees it, the most interesting projects are not confined to the four wallsof her laboratory. “I used to work on more ‘focused’ projects—‘my own’projects, more ‘singular’ research,” she says, the quotation marks clearlyaudible in her voice. But since she discovered the power of genomics, themost exciting way forward has been through ambitious collaborations.Something about her approach seems to be working. In September,Ghedin, 44, was awarded a MacArthur Foundation fellowship–theso-called genius prize bestowed on individuals who show exceptionalcreativity and self-direction in their field. She initially mistook the cryptice-mail message from the foundation as spam—she’d been getting a lotin recent weeks—and quipped to a friend that unless there was moneyinvolved she wasn’t calling this Robert Gallucci guy back. Good thing sheGoogled him and found out he was the foundation’s president.There was, of course, money involved—$500,000, to be exact, nostrings attached. But what made her feel most honored was how recipientsare chosen. “It’s an anonymous nomination, and then they requiremultiple letters of support,” she says. The recognition from people in herfield “was incredibly flattering.”DRAWINGS | LEONARDO DA VINCIILLUSTRATIONS OF SCIENTISTS | ROB KELLYW INTER 2011⁄12 13

GhedinHer colleagues say the award is richlydeserved. “Technically, she’s outstanding,”says Eddie Holmes, a molecular evolutionistat Pennsylvania State University who hasworked with Ghedin on sequencing influenzagenomes for the past seven years. And yet, hesays, “there are many people who work in thetechnical stuff, but Elodie also has an amazingability to understand the biology and the evolutionand the bigger-picture stuff, as well.”In the early 1990s, for her master’s degreein environmental studies at the Universityof Quebec in Montreal, Ghedin traveledthrough villages in rural West Africa measuringthe bacterial and chemical content ofdrinking water. “There were tons of parasiticdiseases,” she recalls. “I saw cases ofelephantiasis, leishmaniasis, schistosomiasis.”She came back resolved to study the biologybehind the ravaging force of these pathogens.For her PhD research, she developed apotential diagnostic for leishmaniasis—a projectthat she jump-started in the lab herself,says McGill parasitologist Greg Matlashewski,Ghedin’s PhD supervisor. “She would developthese DNA constructs to express things inLeishmania and control their expression,” hesays, and often he doubted it would work.Almost invariably, though, it did.As a postdoc at the National Institute ofAllergy and Infectious Diseases in Bethesda,Md., Ghedin began to delve more deeply intogenomics. But her first real taste of leading agenomics-based collaboration came in 2005,when as a research scientist at The Institutefor Genomic Research in Rockville, Md.(now part of the J. Craig Venter Institute,or JCVI), she led the effort to analyze thegenome of Brugia malayi, a parasitic wormthat causes elephantiasis. She assembled theworld’s experts on the worm to do so—about50 scientists, each spending a week during atwo-week period lodged in front of a computertussling with their favorite genes. “Everyday, morning to night, we were just sittingthere,” says Sara Lustigman, a molecularparasitologist at the New York Blood Centerwho got to know Ghedin through the experienceand remains a frequent collaborator.Surprisingly, says Lustigman, it was really fun.“It was really an example of how she extractsthe best from people,” she says.Ghedin’s six-member lab at Pitt appliesinnovative genomic techniques to an arrayof very small troublemakers, including B.malayi, viruses like influenza, and microbes.Ghedin, who maintains a joint appointmentat JCVI, credits this mix of systems as a majorsource of inspiration. In lab meetings, everyonein the group weighs in on the projectsunder way, and often the best ideas comefrom people who are working on a differentorganism. “I think that’s creativity, when yousee connections that are not obvious,” shesays. “And for that, it helps to cast a very widenet in your research.”Ghedin plans to use her MacArthur awardmoney to advance her work with B. malayi.Finding ways to kill the worm has provenvery difficult. It is itself infected with a parasite—anintracellular bacterium that is necessaryfor its survival —and these symbioticpartners trick the host immune system intooverlooking them both. Ghedin aims to identifyproteins secreted by the worm and startto dissect their immunomodulatory talents.Because parasitic diseases like elephantiasisdon’t affect many people outside the developingworld, she says, “that’s where I alwayshave the most trouble getting funding.”On the flu-virus front, Ghedin and collaboratorshave most recently been tracking howthe composition of strains in a viral populationmutates and how the virus is transmittedbetween hosts. In a virus like HIV, thatchange is dramatic throughout the manyyears it inhabits a human host. Influenza,though, generally infects individuals for aweek, tops, so much less variability would beexpected, but no one knows for sure.“It’s such a basic thing to understandabout the dynamics of that virus,” she says.“We are designing vaccines with no idea ofwhat’s going on.” —Alla KatsnelsonIn 2005, Ghedin led the effort to analyze thegenome of Brugia malayi, a parasitic wormthat causes elephantiasis, the first of her manygenomics-based collaborations.14

CREATIVE FEARLESSNESSAND OTHER SIGNS OF LIFEA CONVERSATION WITHJEREMY BERG AND GEORGE WHITESIDESDuring the University of Pittsburgh’sScience2011, we pulled aside GeorgeWhitesides and Jeremy Berg, pliedthem with a couple of beers (courtesy of Pitt’s N.John Cooper, dean of the Kenneth P. DietrichSchool of Arts and Sciences), and asked fortheir perspectives on what makes genius happen.Whitesides, who gave the Provost Lectureat the science festival, is the Woodford L.and Ann A. Flowers University Professor atHarvard University. The chemist by trainingis known for his astonishing breadth of inquiryand ability to contribute to many fields,including nanotechnology, microfabrication,and microfluidics. (He has authored morethan 1,100 publications.) Berg, Pitt’s associatesenior vice chancellor for science strategy andplanning and visiting professor of computationaland systems biology, is highly regardedfor his work in molecular recognition processesand for his scientific leadership. Until earlierthis year, he directed the National Institute ofGeneral Medical Sciences. (To read more aboutBerg, see our profile on p. 22.)BergJEREMY BERG: So onething that we’d like totalk about is creativity,and what leads to creativity.And one thing thatI have always admiredabout your work is thebreadth of fields whereyou’ve made creative contributions.Clearly it’s notthe sort of genius wherea person has a flash ofinsight, [but rather wheresomeone] does the samething over and over againin a clearly intentional, systematic way. So I’dbe interested in your strategies and what youthink has led to your successes.GEORGE WHITESIDES: I think there are twothoughtful, well-considered strategies in this,and I would say the first is simply laziness. So,one definition of creativity is doing somethingthat other people don’t do. The nice thingabout working in areas where other peoplehaven’t worked is you don’t have to read theliterature, … and you can do it according toyour own pace. …I’m a big believer in the notion [of startingfrom] something that you think is interestingand emotionally engaging and something,ideally, that other people aren’t doing. So ifyou have a problem that has that characteristic—ifyou look around, and you see evidenceeverywhere, you can pick problems in health,you can pick problems in the environment,you can pick problems in just phenomenologyof nature, and start with something—Wheredoes lightning come from? How do we actuallyincrease the lifespan? What do you do tomake pure water? Those are all interesting,good problems that people care about. Andthe idea of starting from something that’salready in the literature strikes me as just anintrinsically bad idea. If it’s already in the literature,why are we wasting taxpayers’ moneydoing it?PITT MED: How do you develop an ideawithout relying on the past as a foundation?WHITESIDES: The thing about science that’sso wonderful is you don’t have to be particularlysmart to do good science. If you pick agood problem, nature does it for you. …There are other fields of science where that’snot true. You can’t be a [standout] mathematicianwithout being a really, really goodmathematician. You couldbe a very good chemist orbiologist without beingbreathtakingly smart.BERG: Just to pushback on what you said:Obviously what you talkedabout today—protein/ligand interactions and drugdesign—is something a lotof people have thought alot about. But what’s certainlyone of the messagesI got from your lecture is“Don’t believe everythingWhitesidesyou think.” That, youknow, questioning the sortof underlying assumptions that have beenmade and digging into the fundamentals canlead you in interesting directions.WHITESIDES: Yes, but there’s also anotherthing about that problem, and that is weknow that people have been trying to designligands to fit proteins for as long as you and Ihave been in the business. And, you know, itdoesn’t work. Basically, retrospectively, peoplewill claim success, but it basically doesn’twork. And when smart people well equippedwith the best tools available try at somethingfor years or decades and it doesn’t work, youbegin to get the idea that there’s somethingunderlying that’s wrong. So in that particulararea, it’s a little bit of a special circumstancebecause the relation of water and biology isactually a big, important problem, and I don’tthink that anybody would argue that. Andthere’s been something wrong with our abilityto understand how molecules interact inbiology—which means in water. And we’vetended, because we didn’t know how to doW INTER 2011⁄12 15

it, to neglect the solvent part of it. ... So, wewere, in the [Thomas] Kuhn sense, that is“the nature of scientific revolutions,” we wereforced to look at water. But not smart in lookingat water.And Kuhn has a notion, which is thatrevolutions in science occur only in specialcircumstances, and those circumstances comefrom the fact that scientists are just as lazy asanybody else. And most scientists … basicallymake sausage. They repeat work, or extendwork, or do whatever they’re doing, whichis fine. But every once in a while, the theorythat’s available and the importance of thethe laws of electromagnetism in biology areexactly the same as the laws of electromagnetismin physics or in circuit theory oranything else. You get it early, you’re thenprepared to talk to anybody, for one thing.And [you’re able] to do research withoutdoing truly stupid things. My entire careeras a consultant has been spent doing onething, to ask the question—basically, Doesthe proposed project violate the second law ofthermodynamics? And, frequently, it does.When it does, you can say with perfectconfidence, You should not do this because itwill not work.“I think we don’t have all the tricks, all the basics, of understanding biology.”problem [are] such that you find the theorysimply does not explain what’s there. You can’tget it to work. It won’t work. Then somebodyhas to sit down and try to figure it out. If youcan figure it out, if it is figure-outable, andthere is a new direction, then that becomes arevolution.A classic example is quantum mechanics—where, in 1900, physics was regarded as deadbecause Newton’s laws explain mechanics,and the laws of Maxwell, Maxwell’s equations,basically explained electricity and magnetism.The only problem was there wasa little phenomenon called the ultravioletcatastrophe, where distribution of power radiatedby something didn’t fit with what waspredicted. [So when you did] the simpleexperiment in which you took a prism and aslit, and you took the solar light and spread itout on a wall and instead of being perfectlycontinuous, there were these funny blacklines. There was nothing in the theory at thatpoint that explained the black lines. And tryas you might, you couldn’t get a consistenttheory to explain the black lines. So whathappened in 1925 was this flurry that led toquantum mechanics. Quantum mechanics[didn’t say] that Newtonian mechanics andMaxwell’s equations were wrong—in fact,they’re right—but that there’s an underlyingstory which shows that [there are] other thingsgoing on underneath that we hadn’t known.And I think there’s the same kind of thing inbiology. I think we don’t have all the tricks, allthe basics, of understanding biology.PITT MED: Is there a way to prepare a mindto notice these things?WHITESIDES: One of my views is that theway you prepare people to do that is youencourage them when they’re in the stagewhere they can be encouraged not to be timid.That is, find something that you thinkis important where the answer isn’t actuallyknown. Then the encouragement you can giveas a research director is, “Go try it. If it’s possible—you’reas smart as anybody—then it’llwork. …” It won’t work every time. But forgood people, it basically always works.BERG: One issue, which I think is reallyimportant in thinking about education,is many problems that are interesting andimportant are at the interface between traditionallyseparate fields. So the temptation isto work at an interface, but that only works ifyou actually know a lot of the fundamentalsabout one side of the fence or the other. In mycase, I had just the luck of being completelyconvinced I wanted to be a chemist then[discovered] biology later on. So I learned alot of fundamental chemistry, including frompeople around here, then moved into biology.… So that gets you a leg up on a problemwhere you can apply a new tool. So the idealtraining environment: You don’t let peopleknow where they’re going to go, train themin one field, and then say, “Now you can lookbehind the curtain and find out what the newdirection is.” The danger with [being too]interdisciplinary is teaching people a lot aboutthe border between two fields … is great forthe next three or four or five years where that’san interesting frontier, but when that problemgets solved, then they don’t know enough togo find a new one.WHITESIDES: There are things that as ascientist you actually have to know. You haveto know thermodynamics. You have to knowsomething about descriptive metabolism andrelated things. You have to know how catalysisactually works. You have to know the fundamentalsof statistical mechanics and quantummechanics. You have to know somethingabout electromagnetism. These are all hardsubjects that require bending your mind. ButBERG: In physics and chemistry, what youneed to know is well defined. One thing Ilearned moving into biology and medicine isthat … the same level of information is notquite as fundamental in terms of being ableto write it down as facts or equations. … Iwould come up with these wonderful theoriesand would talk to a real developmentalbiologist who would say, “That can’t possiblybe right because, you know, it wouldn’tpredict this and this and this—and those areall known to be absolutely true.” So there’s abase of knowledge in lots of fields you needto master in order to avoid doing things thatare just silly.WHITESIDES: There is another side of this,though. The word that I’ve come to be veryunhappy with is the word “apprentice.” Wehear this often in science—that a graduatestudent is an apprentice in the researchgroup, and that he’s learning the techniquesof the master. It’s exactly the wrong way todo it, because the issue is that the master isthe master of whatever—the master is masterin that time and place—and five years later,it’s going to be something else.I think the master class environment inwhich [a young person does] something with[a senior person] who really knows how todo it well, and [the senior person] helps youto do it rather than teaches you how to doit, is the right way of doing things. And thegreat thing about the U.S. system, at least inthe past, has been that as a young, independentinvestigator, as an assistant professor,16 PITTMED

you could go do what you wanted to do. Ihave to say that I’m a little worried right nowthat there’s so much emphasis on gettingmoney that people begin to try to game thesystem as opposed to doing what they reallywant to do. That’s pretty troublesome to me.BERG: I would second that. I was alsoblessed with supervisors and mentors whowould give me the freedom to go off anddo things and make mistakes. It’s a lot likeparenting. … You know the mistakes to bemade, but you want somebody to feel comfortableexploring … and if they’re heading… onto the freeway, you go over and sort ofnudge them back away from it.WHITESIDES: Either that, or if you notethey’re having problems staying off the freeway,maybe the freeway is the right place.BERG: I think the fear, and I share [your]concerns, is that if you build cautiousnessand timidity into the system, you’re going toseriously limit what comes out the other way.… When I was in the NIH, we were involvedwith developing a couple of programs. Andone of the things that was most satisfyingabout the programs—they were intended foryoung investigators and highly innovativeprojects—was I got several e-mails and phonecalls from people who didn’t get [one] award,saying, It was so much fun to write about what Ireally want to do as opposed to what I thought Icould get funded to do. And it really helped.WHITESIDES: What I tell my students isthat what I want them to do is to come to meand astonish me. To come with an idea I justnever would have thought of myself. And theydo it regularly.—Interview with Joe MikschWATCH FOR THE PITTMEDCASTON ZINIO’S ONLINE NATIONALNEWSTAND.ON INSPIRATIONWITH J. CRAIG VENTERVenterJ. Craig Venter received the Dickson Prize in Medicine this year at the University ofPittsburgh’s Science2011. Venter is founder of the J. Craig Venter Institute (JCVI) and isarguably one of the nation’s most productive scientists. His teams at JCVI and elsewherehave developed genomic tools that are transforming medical science by taking on ambitiousprojects like decoding the human genome, the first human diploid genome (Venter’s), and 165genomes from microbes in the world’s oceans. One of his teams has also created organisms fromsynthetic genomes—he foresees a future in which scientists can “write the computer code oflife.” Venter set aside some time for Pitt Med to share his perspective on the nature of inspirationand how to support inspired people. Edited excerpts follow.PITT MED: What do you look for inpeople you recruit whom you hope will domeaningful and inspired work—will makesignificant contributions? I suppose we’retalking about the scientific level, but if youwant to talk about other realms, you can dothat, too.J. CRAIG VENTER: I think the rules arepretty applicable [for all], as far as I can see.Obviously, we start with people who aregenerally bright people. That shows up in allkinds of ways. Genius is such a relative term.Malcolm Gladwell has looked at all differentkinds of intelligence. ...I’ve not known too many, if any, really brilliantpeople who were lazy. So somehow theenergy of doing things plays a big role. I knowI do much of my learning by physically doingthings and by trial and error.I think [with] people that exhibit genius—other than the kind of genius that shows upwith mathematical prodigies or physics prodigieswho make their major breakthroughs outof sheer brain horsepower, usually in theirearly 20s, or 30s at the latest—inspirationcomes from a variety of sources. Mainly frompeople who, you can tell, look at the world alittle bit differently than others. I never con-“I’ve not known too many, if any, really brilliant people who were lazy.”WINTER 2011⁄12 17

sidered being an outsider when you come intoa new field to be a disadvantage.If you’ve read any Sherlock Holmes, youknow that he didn’t keep a lot of trivia in hishead, because he didn’t want to clutter up hisbrain with things. To some extent, that’s whathappens when going through the school system.We learn how to memorize things, andwe clutter things up with lots of memorizationversus understanding systems and askingfundamental questions about them.[He then talks about the fresh perspectivesof young scientists like Pitt’s Elodie Ghedin(who holds a joint appointment with theVenter Institute) and the Venter Institute’sDan Gibson (who figured out how to assembleand synthesize DNA), and how theyused their gifts to contribute to the new fieldof genomics, a field that “didn’t exist longenough for anyone to have any preconceivednotions.”]In Elodie’s case, she applied [her gifts] tomaking a big difference in what we’re doing inviral analysis. I think just a different perspectivehas a huge impact.PITT MED: What about the working environment?Do you put a lot of thought intohow to set up things so you don’t dampencreativity or inspiration?VENTER: I put a lot of thought into that.In part, first off, trying to make it an environmentthat I find healthy for me. I had thisgreat teacher in high school, Bruce Cameron,who was—when I got back from Vietnamand enrolled in community college—talkingabout the creative process. Even in writing it’scontrary to what people think—[that writersare] inspired by misery, living in difficultconditions… His argument was that peopleare at their creative best when their pleasuretanks are full. It’s hard to think about solvingthe world’s problems if you are hungryor sick or tired or constantly worried aboutother things.So I try to keep my pleasure tanks full.[Laughter.]PITT MED: Do you see missed opportunitieswhere organizations may have had well-intentionedideas and instead dampen and quashcreativity? You don’t need to name names.VENTER: Sure. It’s our entire educationsystem. Our university system. And how weconstruct most businesses. …The stovepipe academic model … doesn’twork very well. I think a lot of my success hasbeen from getting rid of those constraints.I find most people really like working onteams and on projects that are much biggerthan anybody but where their uniqueexpertise is actually required and makes adifference.… I think the environment is a very, verykey part of creativity. I think people probablyhave even more creative ideas than even theyrealize, [but the environment might not be]conducive for their expression.PITT MED: What sorts of ways does the academicenvironment quash creativity?VENTER: Well, rote memorization versuscomprehensive understanding. Why? Becauseyou can quantitate it. The same way universities,for faculty promotions, want to countpublications and citations. …I’ve often joked that people prefer thosesystems because they can count and theydon’t have to read. So if you have to actuallyread somebody’s study and understand itand decide whether it has value, that’s totallydifferent from just saying, “Well, 300 otherpeople have cited it, [so] it must have value.”Even if 300 other people are citing it and saying,“This is a great example of crap.”[Also], this is a nonscientific notionfor someone who is a geneticist and whosequenced the human genome—but brightpeople have bright eyes. It looks like there’s alight on in there. [Laughter.]THE FIX FOR FIXATIONTo boost creativity, beware the psychological phenomenon of fixation, warnsinnovation expert Christian Schunn, a PhD and Pitt professor of psychology,learning sciences, and intelligent systems who studies problem solving andcreativity as a senior scientist in the University’s Learning Research andDevelopment Center. “The first idea that comes to mind can block your abilityto come up with other ideas,” he explains. “One answer can get stuck inyour mind, even when you know it’s a bad solution.”He offers these tips to avoid fixation:… I think being in the Vietnam Warfrom a very young age had a huge impacton the rest of my life. Because you learn inwar, certainly the biggest thing you have tolose is your life. And once you get past that… It certainly changed my risk outlook onthings. I’ve not been afraid to fail or walkaway from things. I’ve rebuilt my career afew times. [Laughter.] I think that it’s reallyamazing in science the number of peoplewho are actually afraid to do the experiment.Whether it’s fear of failure or fear ofsuccess, a lot of people in science can’t bringthings to closure. They will drag on a sixmonthstudy for 10 or 20 years.PITT MED: Think about what it must havebeen like for someone like Thomas Starzl,a surgeon who cared about his patients,to take the risk. Of course, these [patientsconsenting to experimental procedures] areusually people who have no other alternatives.But it must be scary to be the onewho could immediately end a life becauseof trying something new.VENTER: But how much worse is it tonot try?It looks like optimism and pessimismare probably genetic traits. I think I’vebeen quoted on this before: It’s usuallythe optimists that accomplish things. Youhave to have that life-affirming energy.—Interview with Erica Lloyd Put a twist on the classic brainstorming scenario where a group gathers infront of a whiteboard as a facilitator scrawls the ideas each person calls out.“That way is pretty much guaranteed to produce fewer ideas,” says Schunn.“Once people see someone else’s ideas, they get stuck on them.” Instead,have everyone jot down suggestions first by themselves, then compile andreview them together. Likewise, when doing a literature review, instead of having everyone18 PITTMED

WING COVERED WITH A CLOTH AND MOVED BY MEANS OF A CRANK WINCH; BELOW RIGHT, DETAIL OF THE WINCH. CODEX ATLANTICUS, LEONARDO DA VINCI. © VENERANDA BIBLIOTECA.on the team read everything, divide into subgroups thatdevelop expertise in a particular realm of the problem.When the groups come back together, they’ll enrich oneanother’s thinking. “When you have people drawing from abroader pool of analogies, there’s more you can draw on,”he says. “Spreading the literature review around is a wayof not getting the core thinking stuck on one similar path.” Try new metaphors. For example, if the problem isviral infection, consider re-framing the problem as “howthings get in,” opening your mind to such concepts askeys in locks, basketballs thrown through hoops, andeven groundwater seeping into a well. “If you think aboutthe problem in very specific ways,” Schunn explains, “theproblems that are already associated with it come to mind.By categorizing your work as a more general problem, itfrees up associations to more general solutions.” Don’t go in too deep too soon. For example, Schunnpoints out, computer modeling can demonstratebriskly whether a research approach is headed in thewrong direction, saving time and money. Yet simulationsdemand a level of detail that can pull a scientistdeep into the weeds early in the process. “You can getstuck thinking about the details and prevented fromthinking in more general ways,” Schunn cautions. “Goback and forth between a very detailed model and justsketching it out on paper or some way that’s purposefullysloppy so you can think in more general ways.People can get very attached to the specific thing theybuilt on the computer and lose the forest, as it were.”—Sharon TregaskisW INTER 2011⁄12 19

GREATERTHAN THE SUMPITT PEOPLE: BETTER TOGETHERMurat Can Cobanoglu, who trainedas a computer scientist in Istanbul,applied to graduate school withthe intention of one day upending the drugdiscovery process.Now, as a PhD student in the jointUniversity of Pittsburgh School of Medicine/Carnegie Mellon University computationalbiology program, he seems to be off to a goodstart. Cobanoglu is certainly energized by theweekly lab meeting in Room 3065 of Pitt’sBiomedical Science Tower 3, where he musesover microscopic goings-on with a crew ofdisparate members that includes engineers,chemists, and physicists.“When a chemist looks at a drug compound,he has insights someone else mightnot have,” says Cobanoglu, who has beendeveloping in silico models to predict drugproteininteractions. “[I] look at the computationalmethods. And the physicist looks atthe interactions between the molecules in amolecular dynamics simulation and again hasa valuable insight.“When you combine each of these differentpeople with their different backgrounds, itmakes for an excellent and very fun environmentand super-creative lab meetings.”The spirit of what’s happening in Room3065 can be found across campus. Whenspeaking with new Pitt med recruits, as well aslongtime faculty members, what often comes upis how extraordinarily welcoming the environmentis to collaboration. Some have suggestedit’s a Pittsburgh thing—the task-oriented bent ofpeople who choose to live and work in a rust belt/near-Midwest city.“[In some academic towns], they don’t eventalk to each other in their own departments. Theytake it as a point of pride,” says Christian Schunn,a PhD professor of psychology, learning systems,and intelligent systems, who studies problemsolvingand creativity as a senior scientist in Pitt’sLearning Research and Development Center. Hesays Pittsburgh thrives on a “help-your-neighbor,talk-to-people-on-the-street sensibility.”Schunn may be on to something, but there’salso strategic thinking behind the culture that hasarisen.A collaborative ethos seems to have seepedinto the soul of this medical school at least sincethe late Thomas Detre, who oversaw Pitt’s healthsciences from 1984 to 1998, began breakingdown territorial strongholds by building institutesand centers. Observers say that the academicenvironment has become optimized in the lastdecade in a number of ways, from the “open lab”20 PITTMED

RULES FOR THE CREATION OF THE GEOMETRICAL GAME (LUDO GEOMETRICO) FROM CODEX ATLANTICUS, LEONARDO DA VINCI (1452–1519). © VENERANDA BIBLIOTECA.design of new facilities to deciding who willlead programs. “There’s a great deal of thoughtinvested here to build the best teams and buildan environment where there are no barriers,”says Joan Lakoski, associate vice chancellor forscience education outreach, health sciences, andprofessor of pharmacology and chemical biology.“We never worry here at Pitt about wheresomeone is housed. We just say so-and-so is thebest, and we pick up the phone and talk to them.”She says that Arthur S. Levine, senior vicechancellor for the health sciences and dean of themedical school, delights in his work as a talentscout. “He gets the best minds and brings themtogether.”When Simon Watkins joined Pitt’sfaculty in 1991, advanced imagingwas considered technically demandingbut not much more. The young scientist,now a professor of cell biology and physiology aswell as of immunology, intended to establish theintellectual rigor of his field.“I had this vision of building a center thatwould be at the edge of what you can do withoptics and microscopes and computers,” saysWatkins, who founded the Center for BiologicImaging shortly after he arrived and has overseenits growth into a 20-person research staffthat works with scientists from across campusand around the world. “I was always given theresources to build that dream.”Early in his own tenure, Watkins was integratedinto multiple investigations that continueto this day by senior faculty who already hadestablished projects and funding streams. “Wetend, generally, to cut the pie into thinner slicesand get more people involved,” he says.Watkins is a scientific partner in an astonishingnumber of studies—he himself is “veryactive” in 60 or 70 at the moment, and his groupis contributing to perhaps 250. His is a specialcase because other labs rely on Watkins for cellularimaging expertise, yet, Lakoski notes, theUniversity has made the financial piece for himand others “virtually seamless, which offers tremendousflexibility.”“No one is bean counting,” she says. If facultyget together to apply for a grant, the collaboratorsthemselves agree on the division of labor and themoney follows that plan.“In fact, you are rewarded for taking risks,”Lakoski says, pointing out pilot programs andbridge funding pools that reward collaborativeactivity. “A number of funds are designed tobring clinicians and basic scientists together.”Watkins says it’s important to think aboutsynergy when bringing in new people, too.“We look at how [prospective hires] fit or fillthe needs of the larger medical campus,” saysWatkins, comparing the mindset to that of alandscaper choosing new plants to enhance anexisting garden.“Because we know where people will fit, weknow whom they’re going to collaborate withwhen they come here. There’s nothing worsethan bringing in [junior scientists] and thenisolating them in their own lab.”As medicine and science get morecomplex, investigators and physiciansneed to be able to turn to sophisticatedcolleagues with differing expertise. Andwith federal funding getting sparser, they willhave even more incentive to partner. Thatsaid, even with support from on high at Pitt,there’s plenty to finesse on the ground.Cobanoglu’s mentor, PhD scientist IvetBahar, traveled from Turkey to Pittsburgh toestablish a Center for Computational Biologyand Bioinformatics in 2001. Her first few yearshere weren’t exactly a walk in the park.“When I joined this university, I was frustratedabout not being able to speak the samescientific language with many people here,”says Bahar. So she proposed, with the encouragementof Levine, that the school form whatis now the Department of Computational andSystems Biology (systems biology being thefield that uses modeling to investigate howthe whole—whether a mol ecular system oran organism—is bigger than the sum of itsparts). The department would bring togetherfaculty with expertise in biology, chemistry,engineering, immunology, math, and physics.A year after the founding of the department,she campaigned successfully for the formationof the school’s joint PhD program incomputational biology with Carnegie Mellon(Cobanoglu’s program)—another step in theprocess of building a common vocabularyamong scientists from different fields.Bahar requires that each member of hergroup develop a fluency in the language ofcomputational biology: Imagine the UnitedNations conducting business exclusively inKlingon instead of using translators to bridgethe chasm.“It makes for super-efficient communicationand collaboration,” says Cobanoglu.“What brings us together is the greatopportunities in this field right now … in thepost-genomic era,” says Bahar, the John K.Vries Professor and Chair of Computationaland Systems Biology. “We are all excitedabout our ability to solve some longstandingproblems.”“The literature shows that teams composedof diverse individuals with different technicalbackgrounds—backgrounds in terms of wherethey trained, different outlooks—outperformindividuals every time,” says Lakoski.Yet, the hazards of miscommunicationamong those trained in different fields aresubstantial.“If you have a way of dealing with the processof getting to common ground, the overalldiversity is helpful,” says Schunn. “But a lot ofsmart teams go down in flames because theycan’t resolve their differences.”To head off probems before they start,Schunn advocates face-to-face meetings earlyin a collaboration. “You need to be able todraw, point, and follow up on quizzical looksin ways that the telephone or Skype just aren’tgreat for,” he says.Such contact also builds trust. “If you hangout with people and get to know them, youcan come to a different ability to understandwhy they did something differently from theway you might have done it.”Lakoski, who gives the first lecture in anannual course on team science (yes, there’sa course) for clinical and research facultyfrom all of the health sciences schools, says,“Team science takes longer because you havearguments, people don’t understand each other’sperspectives, and, until recently, peoplehaven’t had training. It’s not like you swallowa pill, and suddenly you’re a team scientist. Ittakes practice.”Pitt is educating its future clinicians alongthese lines, as well.Like research, caring for patients is ajoint effort more than ever today. So theUniversity’s health sciences schools have beenbuilding awareness of the importance of crossdisciplinarycommunication as part of the curricula.In 2010, a team of students from theschools of pharmacy, nursing, and medicinetrained together to compete in an interprofessionalcompetition at the University ofMinnesota. It was Pitt’s first time sending ateam. In the contest, the Pitt students spenthours on a fictional post-mortem. Then,before a panel of judges, they presented theiranalysis of what led to the death and a proposalfor how to avoid similar outcomes. Groupsfrom nine institutions competed.Guess whose team took home the top prize.—Sharon Tregaskis and Erica LloydWINTER 2011⁄12 21

COURTESY J. BERGJeremy Berg, lauded by many for his leadershipin the basic sciences, will keep an activelab at Pitt. He now studies compartments inhuman cells called peroxisomes. The contentsof these compartments may depend on a competitionbetween different proteins for a specificreceptor that carries the proteins acrossa membrane (shown here as pink-and-greenlayeredribbon) into the interiorof the peroxisome.22 PITTMED

FEATUREJEREMY BERG, A RISING STAR AT NIH,COMES TO PITT | BY REID R. FRAZIERTHENATURALWhen he was a young assistantprofessor at Johns HopkinsUniversity, Jeremy Berg’s gradstudents could hear him coming before he walkedin the door. So eager was he to start the nextactivity, the scientist made a habit of runningbetween meetings. John Desjarlais, a PhD studentin Berg’s lab, remembers hearing the elevator dooropen and the sound of the 6'2", wide-shoulderedscientist bounding toward him. “You’d hear thisfreight train coming down the hall. He would literallysprint down the hallway,” says Desjarlais, nowvice president of research at Xencor, a Californiabiotech company that engineers proteins. “We allknew not to open any doors when we heard this.”W INTER 2011⁄12 23

COURTESY J. BERGBerg’s haste couldbe forgiven. He wasbusy making eyepoppingdiscoveriesabout the structures oftranscription factors,proteins that activateDNA. Berg pioneeredthe study of zinc fingers,molecular toolsused by transcriptionfactors to identify binding sites on DNA. Hewas extremely curious. He was enthusiastic.He’d spend hours in his office bending a wiremodel of a protein structure to get the shapejust right. He’d do experiments with proteinsjust to see what happened. (He once askedDesjarlais to add cobalt to an insoluble zincfingeranalog—just to confirm that it wouldturn blue. It did.)What propelled him down the halls ofJohns Hopkins sustained him during a runto the upper ranks at the National Institutesof Health (NIH). At the age of 45, he wasnamed director of the National Institute ofGeneral Medical Sciences.In his eight years as head of NIGMS, Bergbecame a leading thinker in how to fund sci-Berg predicted the structureof zinc fingers, whichare now customized byscientists to “knock out”DNA sequences.Medicine. “He’ll help me make our institutionas competitive as it can possibly be.”Levine first learned of Berg’s interest inPitt in late 2010, when he got a letter fromhim.Was there any work for him in Pittsburgh?Berg wanted to know.“I would have to admit I was surprised,”Levine says. “Dr. Berg is a terrific scientistand a terrific scientific leader. He is seenalmost heroically by the national scientificcommunity.”It is rare for an NIH director to knock atyour door. But Berg’s situation was unique.His wife, the influential radiologist WendieBerg, was being recruited at a number of differentuniversities around the country. Couldany of them find a job for her trailing spouse?“A lot of other places were kind of not surewhat to do with me,” Berg says.Levine’s answer to Berg’s query? “Ofcourse.”Who wouldn’t want Berg’s help? A quickscan of his CV reveals a stellar career. But reallythe proof is in the respectful tone former colleagues,bosses, and students get when speakingof Berg.Zerhouni first met Berg when the two menworked at Johns Hopkins, where Zerhouni wasthe American Society for Biochemistry andMolecular Biology.GOING UP, IN A HURRYBerg began this life of curiosity as a Stanford facultybrat. His father, Paul Berg, was a mathematician,and his mom, Judy Nadell, a hematologist.For his 12th birthday, Berg’s father gave himThe Architecture of Molecules, an illustrated bookcoauthored by Nobel laureate Linus Pauling andartist Roger Hayward. The book portrayed moleculesin pastel ball-and-stick drawings. It waschemistry made visible, and the young JeremyBerg understood just enough of it to get hooked.As an undergraduate at Stanford, he migratedtoward chemistry. Among his teachers there werestructural chemist Keith Hodgson, biochemistLubert Stryer, and inorganic chemist RichardHolm. He learned X-ray crystallography fromHodgson. Holm was interested in modeling theactive sites of metal-containing enzymes, particularlythose containing molybdenum. (Thiselement allows enzymes to promote key reactionssuch as the conversion of nitrogen gas to ammoniaand the conversion of xanthine to uric acid.)“He was extremely skilled in determining 3-Dstructures of molecules using X-ray defraction,”Holm says. “Mind you, this guy was a freshmanBerg asked a colleague at Hopkins how many times someone had predicted aprotein structure. “If yours is correct,” his friend told him, “that would be one.”entific research, spread grant money to morelabs, and encourage creativity in science. Hechampioned high-risk research, young investigators,and diversity. “He was one of the besthires I ever made,” says the man who broughthim to the agency, former NIH director EliasZerhouni.This year, Berg made a quick turn in his runas he came to Pitt to become the University’sfirst associate senior vice chancellor for sciencestrategy and planning for the health sciences.Berg will continue his research as professor ofcomputational and systems biology. In generalterms, Berg’s job will be to think deeply aboutbiomedical science at Pitt. How to do it better,how to do it creatively, and how to get youngscientists the training and resources they need.“I see his role being very similar to the rolethat he had at NIH, which is to participatewith me in the planning and strategizinginherent in science,” says Arthur S. Levine,Pitt’s senior vice chancellor for the schools ofthe health sciences and dean of the School ofvice dean for research. The two men workedtogether when Berg headed Johns Hopkins’Institute for Basic Biomedical Sciences, whichcoordinated scientists from across disciplines.“In that position, he really was a leader—you could tell,” says Zerhouni.“He was open to understanding thedynamics of research outside his own field.”At NIH, Berg drew attention for his frankand open discussions about the agency’s challenges.He started its first blog. Earlier thisyear, he made waves as the lone dissenteron a vote that, among other implications,would likely close NIH’s National Centerfor Research Resources, a home for basicand translational science for decades. Bergthought NIH hadn’t thought the decisionthrough enough and said so. The vote was12-to-1 in favor.Berg nonetheless gained respect from scientistsfor speaking his mind. “He has greatintegrity to stand up for his convictions,”says Stanford’s Suzanne Pfeffer, president ofor sophomore; and this is the kind of techniquethat graduate students, some of them, don’t learnvery well, ever.“He was a brilliant student, one of the mostoutstanding undergraduates I’ve ever seen, anywhere,”says Holm, now a professor of chemistryat Harvard. Working with Hodgson and Stryer,Berg, at 21, coauthored a paper in Nature.Berg got a PhD in chemistry at Harvard,working with his old Stanford professor afterHolm moved his lab to Cambridge, Mass. Holmasked Berg to create molecules that would simulatethe reactivity in addition to the structuralproperties of the catalytic sites of some molybdenum-containingenzymes. Berg developedsuch a system, one of the first reactivity modelsin bioinorganic chemistry.Pure chemistry wasn’t Berg’s primary interest—hewanted to work in biology, too. So hechose a postdoctoral fellowship in the departmentof biophysics at Johns Hopkins, where hissoon-to-be wife, Wendie, was getting her MD/PhD. (They met in quantitative analysis class24 PITTMED

at Stanford. His parents also met in college,in quantitative analysis class.) At Hopkins heworked in the lab of Carl Pabo, a young scientiststudying the structures of DNA-bindingproteins.Berg landed a faculty position in Hopkins’chemistry department. As he was preparingto start his own laboratory, a group of scientistsled by Nobel laureate Aaron Klug of theMRC Laboratory of Molecular Biology inCambridge, England, discovered “zinc fingers,”small domains organized around bound zincions within a protein that binds to specificsequences of DNA. They proposed that thezinc fingers determined the DNA sequences towhich the protein binds.This discovery got Berg wondering: Whatdid those zinc fingers look like? If scientistscould understand how zinc fingers were made,they could conceivably make their own. “I hadtime to stare at the sequence and think aboutwhat it might mean,” says Berg. “It was sortof like Tinkertoys. Once you had the buildingblocks, then it was a question of how can youput these together in a way that made sense tothe overall structure.”Berg proposed a structure in which the zincion organized each zinc finger into a unit wellsuitedto bind DNA. This model would allowthe fingers to slide inside the double-helicaltube of DNA at precise positions. This wouldexplain the structures’ ability to bind with suchspecificity and affinity.Berg asked a colleague at Hopkins how manytimes someone had predicted a protein structure.“If yours is correct,” his friend told him,“that would be one.”He published his prediction in 1988. Bergwaited. A year later, a group of scientists atScripps used nuclear magnetic resonance spectroscopyto determine the structure of thezinc finger. There it was; just as he’d predicted.(Pabo’s lab, where Berg had done his postdoc,later became the first to develop the crystalstructure of a bound zinc-finger protein.)In tandem with other technologies, zinc fingersare now used in the creation of “knockout”rats and mice—scientists now design fingers thatrecognize a sequence on the genome they wantto exchange.Berg’s zinc-finger prediction got the youngscientist noticed at Hopkins. Among thoseimpressed was Thomas Pollard, chair of cellbiology. He saw Berg give a presentation. “He’ddone something brilliant, and the way he conveyedit really gave you confidence that he wason top of things,” Pollard says.MARTHA RIALBerg at his new home, the University of Pittsburgh. To learn about his thoughts on buildingan inspiring research climate, see his conversation with George Whitesides (p. 15.)Pollard was on the search committee fora chair in the biophysics department, whereBerg had been a postdoc. Berg was 32, almostpreposterously young for the position, butPollard put his name up for the post anyway.(Pollard was 34 when he became chair of hisdepartment.)“I think I literally said, ‘Why would I wantto ruin my career at such an early stage by gettinginto administration so early?’” Berg saysnow, with a chuckle. Berg thought it mightslow down his research career. But every morning,heads of other departments would stop byhis office, nudging him to take the job. He did.He was among the youngest department chairsin the history of the university.ASKING HARD QUESTIONSJeremy Berg met Elias Zerhouni throughWendie, Zerhouni’s colleague in radiology.He worked closely with Zerhouni on variousintramural committees, and Zerhouniwas impressed by the “ecumenical” way Bergtreated other disciplines. When Zerhouni wasnamed director of NIH in 2002, he had tofill several leadership positions. A search committeeforwarded him several names for theNIGMS job. One of them was Berg’s.NIGMS holds a special place in the heartsand minds of basic scientists around theworld. “It’s probably one of the most criticalinstitutes, because it funds science at theedge,” says Zerhouni, who is now president ofglobal research and development for Sanofi.“It’s where the frontier of knowledge is created.”Unlike most NIH institutes, NIGMShas no disease focus. Along the continuum ofbench to bedside, it is the most “bench” of allinstitutes.For the position, Zerhouni wanted someonewho was committed to what he called“transformational” research—high-risk, highrewardscience. When he interviewed Berg,he got an earful about some of the agency’sshortcomings in this regard. NIH didn’t investheavily enough in risky science or lesser-knownW INTER 2011⁄12 25

and younger scientists, Berg told him. “He feltthe NIH peer review was somewhat conservativeand that it should truly encourage breakthroughresearch,” says Zerhouni. On thisthe two men agreed, and Zerhouni eventuallyconvinced Berg to take the job in 2003.It didn’t take Berg long to make his mark onthe agency. In 2004, NIH launched the PioneerAward, a pet project of Zerhouni’s. Zerhounihad wanted to fund innovative research, especiallyfrom scientists who may not score ashighly along traditional NIH guidelines. Whenthe first batch of awardees was unveiled, Bergwas disappointed.“I was really looking forward to Googling abunch of people I’d never heard of and tryingothers. “I said, ‘What will you do about it?’”Zerhouni says. “He said, ‘I’ll be more transparent.I’ll tell people, Here’s the funding we have;here’s what we’re funding and why.’”Berg then became the first blogger in theNIH administration. The Feedback Loop,begun in 2009, is a blog that Berg and othersin his institute used to communicate theirmethods to scientists. Berg has blogged abouthow the institute rates and debates grant applications.He published his own studies on thecorrelation between peer-review scores and thelikelihood a grant gets funded.“None of the rest of us do that,” says StoryLandis, director of the National Institute forNeurological Disorders and Stroke. “How bigthe system that determines the appropriatecomposition of proteins within peroxisomesthat leads to proper function.Wendie Berg, meanwhile, will continue herwork on techniques to improve breast cancerscreening. She has led multicenter investigationsinto the efficacy of the techniques. (See “Lessonsin Survival” in the Summer 2011 Pitt Med.)In his science strategy and planning position,Levine envisions Berg working on someof the same topics that interested him mostat NIH—looking for ways to improve diversity,encourage breakthrough research, and helprefine bioscience graduate training.Berg’s experience at NIH will also be of useat a time of economic uncertainty in scienceHow do you get the most bang for the research dollar? How much funding is too much?These are the kinds of questions Berg asked at NIH.to figure out what they were doing and whythey were chosen,” Berg says.The nine awardees were all excellent scientists,Berg says. But they were also well-established,and almost all were older, white men.“I was mouthing off to the deputy director[Raynard Kington, now president of GrinnellCollege] that I thought this was a lost opportunity,”Berg remembers. Kington told himto, essentially, go tell it on the mountain.Berg wrote a long e-mail to Zerhouni spellingout why he thought NIH could take biggerchances with the Pioneer program.“A day or two later,” Berg recalls, “I walkedinto a meeting, they pointed over to me andsaid, ‘How would you like to run the Pioneerprogram?’”Berg accepted the challenge and asked colleagueJudith Greenberg to help administerthe award. The following cycle, NIH didmore to advertise its intention to award highriskprojects and a diverse pool of applicants.Among the next year’s recipients was NathanWolfe, a young public health scientist atHopkins who was interested in tracking downnovel animal viruses in Asia and Africa beforethey “made the jump” to human populations.(Wolfe’s work has since been featuredin The New Yorker and Time; he foundedand directs the Global Viral ForecastingInitiative.) Approximately half the recipientswere women, and several were from underrepresentedgroups.There was another problem with NIH,Berg had told Zerhouni. Many weren’t surewhy it supported some investigations but notshould a lab be to get the maximum productivity,per person or per dollar? We all talk aboutthat, but Jeremy actually did the analysis.”In the spirit of transparency, Berg hasstudied how well the peer-review process correlatesto quality, as measured in publications,citations, and patents. And he’s illustrated theresults with Lorenz curves, Gini coefficients,and histograms.“These are things that people at NIH hadn’tbeen doing or sharing,” says Greenberg, nowdirector of NIGMS. “After he started doing it,more and more of these kinds of analyses arecoming out from other parts of NIH.”Pollard, Berg’s champion at Hopkins andnow dean of the graduate school of arts andsciences at Yale University, wasn’t surprisedabout Berg’s innovations at NIGMS.“He’s absolutely curious about how thingswork, whether it’s zinc fingers or whether it’steaching or whether it’s how the NIGMSruns. And if you’re curious about how theywork, you can try to figure out how to makethem work better.”WHAT CAN BERGDO FOR YOU?The next chapter in Berg’s career beganthis summer, when he moved into his officeat Pitt’s Scaife Hall. Berg will continue hisown research, which in recent years hasturned toward the targeting of proteins toperoxisomes. These are organelles that haveseveral vital functions, including breakingdown long-chain fatty acids and synthesizingcertain lipids. Berg is attempting to decodefunding. His arrival at NIH coincided withthe end of its “doubling” period, in which thebudget increased from $15 billion in 1998to $28 billion in 2002. Since then, the budget—currentlyat $31 billion—has been heldessentially flat.How do you get the most bang for theresearch dollar? How much funding is toomuch? These are the kinds of questions Bergasked at NIH, and they are very relevant in thecurrent funding climate, says Pfeffer, presidentof the biochemistry and molecular biologysociety. (Berg was elected to succeed her aspresident in 2012.) “It’s probably time to ask,‘Are we spending that money as wisely as weshould be?’” Pfeffer says. “Berg has some reallygood ideas about that.”Berg is also putting thought into how tofoster bold, high-risk science at the University.“That’s one of the things that’s attractiveabout Pitt,” he says. “There seems to be a fairlystrong culture of that boldness.“There’s still so much we don’t understand,”he says.“There’s still a lot more to be discovered.There are just many, many examples over timeof people who are working on one problemwho then make an observation that didn’tmake any sense at all at the time, and then hadthe good judgment to decide it was potentiallysomething really important.”If these types of observations and researchersaren’t supported, he says, “you’re going toend up not knowing about whole areas of sciencethat are going to be more relevant in thelong run.”26 PITTMED

COVER FEATURESTORYANDREW LAMBERT PHOTOGRAPHY/SCIENCE PHOTO LIBRARYSTATICTINNITUS IS ONE WAYOUR BRAINS LEARN ATTHE CELLULAR LEVELBY ELAINE VITONEThe Ebers Papyrus, one of the oldest surviving medicaltexts, describes a mysterious condition the ancientEgyptians called “bewitched ears.” Throughout thecenturies, its characteristic ringing, buzzing, hissing, static, or othernoises have cursed such notables as Charles Darwin and Ludwig vanBeethoven—some historians speculate they’re what drove Vincentvan Gogh to cut off his own ear. Today, 10 to 15 percent of thepopulation experiences tinnitus, as it’s now called, chiefly older peopleand those who’ve been exposed to loud sounds, from machiniststo musicians. For some, it’s an occasional nuisance, but for up to10 percent of sufferers, it’s debilitating. With its consequences offatigue, cognitive impairment, and depression, tinnitus is finallygetting its due attention. It’s the most prevalent service-associateddisability for veterans of the wars in Iraq and Afghanistan.WINTER W 2011⁄12 27

There is no surefire cure, though some findrelief in masking their tinnitus with other sounds.“I don’t know what silence sounds like anymore,”said Will.i.am of the Black Eyed Peas in aninterview with The Sun last winter, in which herepeatedly wiggled his finger in his ear and shookhis head. “Music is the only thing which eases mypain. . . . There’s always a beep there, every day,all day. Like now. I don’t know exactly how longI’ve had this, but it’s gradually gotten worse.”In spite of their prevalence, historically, thesephantom sounds have remained just that. Asrecently as 20 years ago, we were looking fortheir source in the wrong place: the ear. (Tinnitusis associated with hearing loss, after all.) Thencame the reports that people whose sense of hearinghad been completely dismantled—cancersurgerypatients whose auditory nerves had beencut—also suffered from tinnitus. This was theultimate proof that it wasn’t the ears that hadbeen “bewitched” at all; it was the brain.Thanos Tzounopoulos, a PhD assistant professorof otolaryngology, recently became thefirst to watch tinnitus in action at the cellularlevel, finally uncovering exactly how some brainsturn on themselves in this way. He’s learned thattinnitus is a betrayal of our biology that’s rootedin the very strengths that have enabled humanity’ssuccess: memory, learning, and adaptability.Ironically, the cellular savvy that made Beethovenarguably the greatest composer the world hasever known also drove him to despair, his mindcaught in a loop of “rushing, roaring sounds.”Tzounopoulos speaks with a Greek accent(he hails from Athens) and an easy laugh. In hisjeans, Converse All Stars, and sideburns, he looksa bit more like a guy on his way to a rock concertthan an international expert in the molecularaftermath of exposure to deafening decibels. Theyoung investigator has been pushed to the mainCOURTESY T. TZOUNOPOULOSABOVE: Thanos Tzounopoulos found that the braincenters that govern our senses are plastic justlike those that enable learning and memory.RIGHT: Principal neurons of the dorsal cochlearnucleus—the first nucleus that ushers soundsignals into the brain. This area is more active inmice with tinnitus than in healthy mice.28 PITTMEDCOURTESY M. RUBIO

PHOTO RESEARCHERSstage in recent months, finding his decadelongstudy of sensory processing suddenlyof interest to the likes of The Wall StreetJournal and NPR. “Whenever my researchhas direct implications for disease, it’s asgood as it gets for me,” he says.Tzounopoulos cut his research teethstudying the hippocampus (the brain centerfor memory and learning) as a postdoc in thelab of Roger Nicholl and Robert Malenka,trailblazers in the field of brain plasticity atthe University of California, San Francisco.It was the 1990s, and the field was ripewith promise. Experts were buzzing oversomething called long-term potentiation(LTP), a phenomenon in which stimulatingindividual synapses causes the strengthof their responses to increase. “It’s a kindof training,” Tzounopoulos says. ThoughLTP was first described in the late 1960s, itsexact molecular mechanisms had remainedelusive, but now, they were finally cominginto focus. Scientists were becoming moreand more confident that LTP was exactlywhat they’d hoped: a mechanisms of plasticity.Learning, at the cellular level.A few years later, when Tzounopoulosbegan his second postdoc, he was eager tocarve out his own niche. He knew he wasWhen loud sounds damage the hairs in the ear that turn sound-wave vibrations (such as thesefrom a musical instrument) into a signal for the brain, hearing is lost. Yet people with tinnitus(associated with hearing loss), find loud sounds unnerving. Tzounopoulos saw this hypersensitivityas a clue that their brains had adapted, trying to make up for what their bodies now lack.going to stick with memory and learning—hewanted very much to understand the mechanismsof this training. But he decided it wouldbe best to center his studies further upstreamfrom the hippocampus, which gets involvedvery late in the process of learning. He settledon the brain’s sensory processing—specifically,the very first structure in the auditory-processingchain, the auditory brain stem. “Becausethere you know what the information is about:sound.”At the time, no one believed the structurewas plastic. The hearing portion of the brainwas just the messenger, everyone assumed—it leaves the fancy work to pros like thehippocampus.But Tzounopoulos noticed that the auditorybrain stem had the same sort of wiring andorganization that characterizes the cerebellum,the site of motor coordination.“It was a gamble,” he admits. But it worked.He stimulated individual synapses in the auditorybrain stem and found LTP there, too. In2009, he published a review of his findings inNeuron at the journal’s invitation.Next, as a great many scientists before him,Tzounopoulos sought to further understandhealthy brain functioning by observing whathappens when it’s not so healthy. In the ’50s,scientists discovered what the hippocampuswas for by talking to a brain-surgery patientwho was incapable of making new memories,Tzounopoulos recalled. So, about four yearsago, he decided to study plasticity in the auditorybrain stem by observing what happenswhen plasticity mechanisms misstep and theplasticity of the brain bends out of control.As far as he could tell, that’s what tinnituswas.When hearing is damaged, the centralnervous system must sense it, he figured.Wouldn’t it stand to reason that the brainwould want to maintain a certain level ofactivity? Could it be that it was trying tofill the silence on its own? It had been welldocumented in imaging studies that in peoplewith tinnitus, the auditory circuitry’s responseto sound is far more pronounced. The systemWINTER 2011⁄12 29

PAGES 30-31: PHOTO RESEARCHERSis fundamentally different in people with thedisorder—perhaps because it’s been trained tobe, he thought. Just as auditory synapses in apetri dish can be trained to rev up. Just as ahealthy hippocampus can be conditioned torecall the lyrics to “Ode to Joy.”“Nature, in a sense, is conservative,” hesays. “Once it’s found solutions, it keepsusing these solutions.”Sound travels in waves, vibrations that arepicked up by the hairs of the inner ear. Thesehairs convert the vibrations to a chemicalsignal, then pass them to the brain throughthe auditory nerve. Inside, the auditorynerve stimulates the dorsal cochlear nucleus(DCN), the first nucleus in the auditory brainstem. The portal to the hearing brain.Once inside, the signal becomes part ofthe constant balancing act that is synapticfunction: Excitatory forces move to increasesignal activity on the one hand, and inhibitoryforces decrease activity on the other.With the stimulation of a sound, the excitatoryforce increases, and a neuron fires. Theprocess continues duplicating along the neurologicalchain, and, eventually, the personperceives sound. But in tinnitus, the neuronsfire without the sound, which Tzounopoulosfigured could be happening for one of threereasons: Either they’re exposed to more excitatoryforce, less inhibitory force, or both.To find out which, Tzounopoulos’ teamused a mouse model of tinnitus. Under sedation,the rodents were exposed to soundsabout as loud as an ambulance siren (116decibels) for 45 minutes. Weeks later, theteam confirmed which mice had tinnitus byconducting startle experiments: The teamplayed for the mice a 70-decibel tone, theninterrupted it, and then resumed it beforesounding a much louder pulse. The healthymice perceived the gap and jerked with surprise;in the mice with tinnitus, however, theirinternal noise masked the silence in that gap.The team then studied brain slices of themice, watching how the synapses respondedwhen they tweaked the balance of excitatoryand inhibitory forces. As it turned out, ampingup the former had no effect. But blockinginhibition did. Specifically, they found,deficiency in the inhibitory neurotransmitterGABA is the culprit in tinnitus.On a fall afternoon in 2011, in hisoffice in Biomedical Science Tower 3,Tzounopoulos cracks open his laptop andpulls up two movie files side-by-side onthe screen: one with an outline of a dorsalcochlear nucleus of a mouse with tinnitus,and the other with the DCN ofa healthy mouse. The cells are renderedwith flavoprotein autofluorescence (FA), atechnology he mastered while a fellow atthe Marine Biological Laboratory in WoodsHole, Mass. Within the mitochondria—thepowerhouse of the cell—are proteins calledflavines, which fluoresce when oxidizedwith use. The brighter the glow, the strongerthe activity.Tzounopoulos clicks PLAY on the healthymouse reel, and a small portion of it flashesred, then dissipates into orange and yellow.“But if you do the same thing in tinnitus,30 PITTMED

Some tinnitus sufferers experience their phantom frequencies as buzzing or chirping sounds,like the song of a cricket (opposite page, converted mathematically into graph form) or cicada(above). Author and radio personality Garrison Keillor finds that cicada serenades mask his tinnitusperfectly. Medicine has no remedy, he wrote in 2007. My only alternative, I guess, is towander the planet in search of cicadas.look what’s going to happen,” he says, hittingPLAY on the diseased mouse model’smovie. This is no small, localized response.“The whole area lights up.” (Tzounopoulospublished his findings in Proceedings of theNational Academy of Sciences in 2011; hepresented these movies at the internationalTinnitus Research Initiative Conference lastsummer in Niagara Falls. See our Web Extrasat pittmed.health.pitt.edu.)Tzounopoulos is excited about the roadahead as he continues to sort out the storyof tinnitus: What are the intrinsic, molecularproperties of cells that dictate how adaptablethey will eventually become? What exactlycauses the decrease in GABA? Is less of itreleased? Are there fewer GABA receptors inplay? Or has the circuitry reorganized itselfso that there are fewer GABA-simpatico neurons?And just what exactly separates thosewho develop tinnitus from those who don’t?And then, of course, there are the therapeuticpossibilities. Based on some very preliminarydata, Tzounopoulos hopes he hasa lead. In recent years, his team discoveredthat a certain neuromodulatory system—thecannabinoid system—is central to all formsof brain plasticity, sensory and otherwise.Further: “This system is very dominant in theauditory brain stem, and it mediates these upsand downs of synaptic strength,” he says.It’s a target that’s worked well in the past.The cannabinoid system—so named becauseits receptors are what cannabis binds to whenthe brain is exposed to marijuana—has alsobeen linked to numerous physiological processes,including appetite, mood, and thesensation of pain. Hence, medical marijuanahas been useful in treating chronic pain,which is now considered an apt parallel totinnitus. Chronic pain is a similar story of thebody betraying itself. “There is some peripheraldamage that leads to a central response,”Tzounopoulos says. “And this response thengoes out of control.”In addition to chronic pain, mechanismsof plasticity have been found to be a drivingforce in addiction, Tzounopoulos points out.“It’s the same mechanisms that wire thereward systems. You get a reward—you feelgood for doing something, so you want to domore of it. Constant abuse messes up thesemechanisms. It’s this learning route inducedto an extreme. The addicted brain gets stuckin that state.”Nature is conservative, Tzounopoulos hasnoted. Rather than coming up with a wholenew song and dance for every occasion, ittends to run through a familiar playlist. WATCH FOR THE PITTMEDCASTTHIS JANUARY ON ZINIO.WINTER 2011⁄12 31

98.6 DEGREESPeople and programsthat keep the schoolhealthy and vibrantBEHINDCHILDREN’S SMILESVecchioneLisa Vecchione (DMD ’00, MDS ’03)dedicated her career to the care of childrenwith cleft palate and other craniofacialabnormalities. In fact, at the time shedied in an auto accident last August at the ageof 44, she had more than 3,000 active cases.Vecchione “became very close with herpatients,” says Joseph Losee, a friend and chiefof the Division of PlasticSurgery at Children’sHospital of Pittsburghof UPMC. “She reallybecame almost part oftheir families.”After earning hermaster’s degree in dentalscience and doctoratein medical dentistryat the University ofPittsburgh, Vecchione completed a fellowshipin cleft-craniofacial orthodontics at NewYork University. In 2004, she returned toPittsburgh as the first director of orthodonticsat the Cleft-Craniofacial Center at Children’sand clinical assistant professor of surgery inPitt’s School of Medicine. Over the last sevenyears, Vecchione built a hospital-based orthodonticsprogram that includes naso-alveolarmolding, presurgical orthodontics, and earmolding. She also led or co-led several studieson cleft and craniofacial conditions inchildren.In her honor, Children’s Hospital ofPittsburgh Foundationis establishing the LisaVecchione MemorialLectureship—“an annualrecognition of her energyand her dedication and hercommitment to those children,”says Losee.—Jessica TitlerRACE TO ONE MILLIONThe Class of 1961 is inching up to onemillion—$1 million in lifetime donationsto the School of Medicine. At theclass’s 50th reunion during Alumni Weekendin May, it was announced that the class had,at that time, donated more than a combined$875,000, establishing the Class of 1961 asamong the highest-donating classes in theSchool of Medicine’s history. The class gavemore than $117,000 in the last fiscal yearalone.Richard Paul (MD ’61), a reunion cochair,notes that Pitt’s telethon program,which he and classmate David Katz wereheavily involved in for many years, helped thecause. When calling up former classmates torequest donations, he and Katz stressed thata large portion of the donations would supportMedical Alumni Association scholarshipfunds. “Nobody could really object strenuously… to scholarship funds for needystudents,” Paul says.The class now seeks to increase its total to$1 million. One class member, who wishesto remain anonymous, provided even moreincentive for the class to reach this grandgoal: He pledged to bequeath $25,000 to theSchool of Medicine upon his death if thatwould bring the class’s lifetime giving total to$1 million or more.The anonymous donor notes, “I wasmoved by the fact that we’re very close to $1million.” —Alexis Wnuk and Jessica TitlerBOOSTER SHOTSADVOCATE FOR INTERNISTSAs they graduate with growing debt burdens(the national average was nearly$144,000 in 2009), fewer U.S. medicalstudents are going into internal medicineand family practice, opting instead for morelucrative specialties. Fewer still plan to pursueinternal medicine research, an area of studythat investigates key questions about thepathophysiology of disease.Hoping to bring budding physicians intohis fold, Frank A. Anania (MD ’88) recentlymade his first gift to the School of Medicine,a five-year pledge worth a total of $15,000.Anania’s gift will support Pitt med studentswho have expressed an interest in internalmedicine and plan to pursue careersin clinical, translational, or public healthresearch. Anania, professor of medicinewho directs the Division of Digestive Diseasesat the Emory University School of Medicine,is both an internist and a physician-scientist.“I don’t want us to become extinct,” he says.“I want to encourage students to go intointernal medicine and … retain them in academia.”—AW and JTNEW ON BOARDAnative of Pittsburgh’s North Side,Eric White is the new director ofdevelopment for the University ofPittsburgh School of Medicine. His earliercareer found him working as an officer forPNC Bank and at the Manchester Craftsmen’sGuild as founder Bill Strickland’s assistant.One of his goals is to help Pitt “attract andsupport the best and brightest through scholarships.Paying back loans is a huge burden formedical students,” says White. —AW and JTTo find out how you can help: emw61@pitt.edu32 PITTMEDWINTER 2011⁄12 32

ATTENDINGRuminations on the medical lifePITT MED WAS HEREThroughout WesternPennsylvania, it seems youcan hardly flip a chart withoutseeing a Pitt med studentnearby. It’s no secret that our emergingphysicians are getting their feet wet all overthis region and beyond. But did you knowmany of our students are also crossingoceans to make a splash?Through senior electives, summerenrichment experiences, and scholarlyresearch projects, our students are divinginto clinical and research work inboth urban and rural settings throughoutAsia, Africa, the Americas, Europe, andAustralia, often in underserved areas. In thelast decade, students have brought medicalsupplies to hospitals and clinics; madehouse calls in Honduras; scrubbed fortransplant surgery in Sicily (at the UPMCaffiliatedISMETT); and confronted suchglobal-health threats as HIV, malaria, TB,malnutrition, and chronic noncommunicablediseases, often amid the challenges of aresource-limited setting.“I appreciated how much waste there isin the U.S. as I saw many patients diagnosedsimply by clinical exam, basic labs, plainX-rays, and ultrasounds,” says CorinneRhodes (MD ’10), who completed a rotationin the Southeastern African nation of Malawiin her fourth year.“Often the complicated tests and proceduresthat we utilize to determine diagnosesare not necessary to bring the patients backto their former state of health,” she says.Last summer, second-year student JeremyKauffman traveled to China with fundingfrom the Medical Alumni Association. In hiseight weeks abroad, Kauffman brought careto people still living in tents more than a yearafter the devastating earthquake in Yushu;to orphaned children with special needs inKunming; and to villagers in rural NangQian—“Rural in the sense of a six-hour drivefrom Yushu along dirt roads over 15,000-footmountains,” he adds. He also assisted a surgeonin Xining for three weeks, an experiencethat inspired him to consider a future in pediatricsurgery, as well as a relevant scholarlyresearch project.“I heard about the summer enrichmentprogram,” he says, “and I was really encouragedby the fact that part of the missionwas to broaden the horizons of the medicalstudents and give them opportunities to growprofessionally and personally. Both of thesewere achieved in my case.”In the past decade, some 350 Pitt medstudents have traveled to 67 countries tolearn about medicine from other perspectives.The map on the next page charts travels from2002 to 2011. —Elaine VitoneCOURTESY J. KAUFFMAN AND A. GUSHCHINJeremy Kauffman (Class of ’14) worked withpatients last summer in several settingsacross China. bottom left: Kauffman (secondfrom the right) helps pull his mobile clinicout of the mud in Nang Qian, China. top left:Teaching English to Tibetan children in Yushu.In her Pitt med days, Anya Gushchin(MD ’09) volunteered at eye clinics in Nepaland India. top middle: Visiting the Taj Mahalafter a month-long medical trek in the mountains.bottom middle: With the village chiefand schoolteacher (holding an ophthalmoscope)of Dodra, India. above: At a seminaron antibiotic resistance Gushchin organizedfor Kathmandu Medical College and ShiganHealth Center in Nepal.WINTER 2011⁄12 33

PITT MED WAS HEREILLUSTRATION BY STACY INNERSTCOMPILED BY ELAINE VITONENATIONS WITHIN A NATIONThirty-four students have worked with indigenouspeoples in North America, includingmembers of the Navajo, Yavapai-Apache,and Hopi nations. They’ve also served withnative Alaskan and Hawaiian communities.SAN JOSÉ DEL NEGRITOShoulder to Shoulder is a nonprofitcofounded by three Pittsburgh docs—two of them with Pitt ties: N. RandallKolb (MD ’82), family medicine residencydirector at UPMC Shadyside, andWilliam Markle, family medicine residencydirector at UPMC McKeesport.The organization has brought some150 students to San José del Negrito,Honduras, in the last decade to providepreventive, primary, and acute careand help with public health initiatives.On their most recent trip this fall, Pittmed students gave well-child exams to600 kids in the area and provided manyother services.LILONGWESince 2001, more than 40 Pitt medical studentshave traveled to Malawi as part of clinicalelectives or to pursue required scholarlyresearch projects. Most spent time at KamuzuCentral Hospital in Lilongwe, where Thuy Bui,Pitt associate professor of medicine, servedas a Peace Corps volunteer physician in 1995.She continues to support training and patientcare there through UPMC’s Global Health TrackInternal Medicine Residency Program. By theway, in 2000, Bui and Pitt assistant professorof biomedical informatics Gerry Douglas (PhD’09), her husband, cofounded Baobab Health, anonprofit that uses technology to improve healthcare in developing countries. So far, Baobab hashelped bring antiretroviral therapy, HIV testingand counseling sessions, imaging studies, andlab tests to thousands of Malawians.34 PITTMED

STUDENT CLINICAL AND RESEARCHTRAVEL EXPERIENCES (2002–2011)1–3 students:Argentina, Armenia, Austria,Belize, Bolivia, Bosnia,Brazil, Bulgaria, Canada, Chile,Colombia, Cuba, Dominican Republic,Egypt, England, Gabon,Germany, Guatemala, Haiti,Hungary, Ireland, Israel, Japan,Lebanon, Lesotho, Liberia, Mali,Nepal, New Zealand, Nicaragua,Nigeria, Paraguay, Saint Lucia,Samoa, Scotland, South Africa,South Korea, Spain, Sri Lanka,Sweden, Taiwan, Tanzania, Thailand,the Virgin Islands, Togo,Trinidad and Tobago, Uganda,Ukraine, and Vietnam4–10: Australia, Costa Rica,Ecuador, Ghana, Kenya, Mexico,Mozambique, Peru, Swaziland,the Philippines, and Zambia11–20: Chinaand the Himalayas21–40: India and theUnited States41–99: Italy and Malawi100 plus: HondurasSOURCE: OFFICE OF STUDENT AFFAIRSPALERMO AND DUBLINItaly has been super simpatico to Pitt meders.Since 2003, 57 have made the trip, most ofwhom based their clinical and research experiencesat Palermo’s UPMC-affiliated transplanthospital, ISMETT. A similar student programis in the works at UPMC Beacon Hospital inDublin, Ireland.SCHOLARS AT LARGEBased on their experiences abroad, studentshave completed scholarly research projectsranging from mass drug administration for elephantiasisin the Philippines to predictors ofinfant malnutrition in Lesotho.HOW DO THEY GET THERE?Students often do their own fundraising to covertheir travel expenses, many of them garneringsupport through Medical Alumni AssociationSummer Enrichment Scholarships and TravelGrants from the University of Pittsburgh Centerfor Global Health.WINTER 2011⁄12 35

ALUMNI NEWSCLASS NOTES’80s Though he modestly claimshe’s “just doing administrative work,” Frank Castello(MD ’82) is anything but your average administrator.Recently named Physician of the Year by NJ BizMagazine, he has been medical director of Children’sSpecialized Hospital, the country’s largest pediatrichealth-care rehabilitation system, for 11 years. Duringthat time, the Mountainside, N. J.–based hospital hasgrown substantially, from treating 3,000 patients in2000 to six times as many today. Castello says, “Themost rewarding aspect has really been the ability tohelp grow programs, recruit physicians, and expandthe services that we can offer to kids.” Those expandedservices include a sophisticated pharmacy systemthat significantly reduced the hospital’s error rate, anew method for priming IV tubes that resulted in 18bloodstream-infection-free months, and the ChronicIllness Management Program, an inpatient programthat teaches adolescents with chronic illnesses how tomanage their health.Byers Shaw (Transplantation Surgery Fellow ’83),one of many Thomas Starzl protégés who’ve gone onto lead transplantation programs of their own, has anew title to add to his CV: prize-winning essayist. InAugust, Shaw—professor of surgery and cofounder ofthe liver-transplantation program at the University ofNebraska—was presented with a $5,000 check at apacked public reading in Pittsburgh’s Garfield neighborhood,which was attended by Starzl and other membersof the Pitt transplant team from the 1980s. Shaw’sessay, “My Night With Ellen Hutchinson,” tells of a livertransplant Shaw performed late one winter night in1983—one of his first without his mentors by his side.The contest was sponsored by the Salt Institute forDocumentary Studies, based in Portland, Maine, andjudged by The New Yorker’s Susan Orlean of The OrchidThief and Adaptation fame. The essay was published inthe summer 2011 issue of the literary journal CreativeNonfiction.Alakananda Basu (PhD ’85) pours a lot of effortinto grant writing—to fund her research in signaltransduction and chemotherapy resistance, certainly,but also to support another pleasure: mentoring. She’sbeen shepherding teen scientists since her Pitt days;as a postdoc she took an 8th-grader under her wing.Now at the University of North Texas Health ScienceCenter in Fort Worth, Basu is a professor of molecularbiology and immunology and graduate advisor for thecancer biology program, which she launched in 2007.Through the school year, her plate is full teaching andmentoring grad students. She spends summers mentoringhigh schoolers in her lab, too—“especially minoritystudents,” she says. This summer, one of her charges,17-year-old Shree Bose, won the grand prize—a $50,000scholarship and a trip to the Galapagos—at the firstGoogle Global Science Fair for a cisplatin-resistanceproject she completed with Basu’s guidance.When pain specialist MarkHashim (MD ’89) volunteeredHashim (right) in Haitito coach his son’s soccer teamin 2010, he didn’t expect that itwould lead him to practice medicinein a Third World country. As ithappened, one of his son’s teammates’fathers was Leo Vieira,cofounder of People for Haiti,a nonprofit that provides basicnecessities and medical care onthe island. Hashim has since traveledto Haiti on two of the organization’sfive-day medical missiontrips, during which medical volunteerstreat up to 1,500 patients.The ailments they treat rangefrom severe infections to physicaldeformities to vision loss. It’s theHaitians’ spirit and thankfulnessthat Hashim says he misses mostafter a trip. “After a while of practicingback in the U.S., you go,‘God, I really need to go back toHaiti again.’” He’s planning to dothat in January 2012.ArnoldWE KNEW YOU WHEN: JAN D. SMITHJan Smith (Critical Care Fellow ’67, Pulmonary Diseases Fellow ’69, Internal MedicineResident ’71), an MB ChB, originally came to Pitt to complete a fellowship in criticalcare medicine with Peter Safar in his burgeoning program. Under Safar’s leadership,Smith experienced a revolution in resuscitation and critical care medicine. He describesSafar as “extremely dynamic” and admits that he “had to run to keep up.” But it can behard to keep up with Smith himself.As a White youth growing up in South Africa under apartheid, Smith knew he had aprivileged life. But in 1961, he was the odd man out. He was working at McCord Hospitalin Durban, South Africa, which at the time was still a racially segregated hospital. Hewas the only White intern. “It was a tremendous social experience,” he says—one thathas remained with him in his decades of work as a professor of anesthesiology, internalmedicine, and critical care medicine at Pitt and in his travels.And travel he does. Smith, a Pitt anesthesiology clinician emeritus (he still teachespart-time), has regularly served as a volunteer physician in several African countries.In South Africa, Smith has helped set up educational programs and works with theUniversity of Pretoria on HIV medicine, TB, and critical care programs. He has alsoworked in Tanzania at Kilimanjaro Christian Medical College, helping to train medicalprofessionals in the delivery of anesthesia care and serving as an external examinerJIM JUDKIS36 PITTMED

COURTESY UPMC’00s Prostate-cancer hormone treatmenttends to follow an unfortunate yet predictable pattern,explains Nima Sharifi (MD ’01), assistant professor ofinternal medicine at University of Texas SouthwesternMedical Center: The patient is given medication toblock testosterone, the staple food of prostate-cancercells, but within a year, the cancer returns. The cancercells’ workaround, we’ve long assumed, is to use aparticular pathway to make their own testosterone,which they subsequently use to produce DHT (dihydrotestosterone),an even more potent superfood. Inrecent years, new drugs have been deployed to blockthis pathway, but many patients’ cancers have provenresistant to these second-line therapies, too.Recently, Sharifi found what appears to be thereason why —a discovery even he didn’t believe atfirst. “We looked at this in six cell models,” he says,“and all six showed the same thing.” (The same wastrue in patient biopsies, he’d later find.) Turns out thatlate-stage prostate-cancer cells use an additional, completelyseparate pathway to produce DHT directly—notestosterone required. The study was published inProceedings of the National Academy of Sciences inJuly. A multicenter, Prostate Cancer Foundation–fundedeffort is now in the works.for the local Tanzanian anesthesia boardexaminations. And Smith has served onmedical missionary trips to many othercountries.“Jan is one of a handful of physiciansI know who has truly dedicatedhis entire life to medicine,” says JohnWilliams, an MD, the Peter and Eva SafarProfessor, and chair of Pitt’s anesthesiologydepartment. “I know very few physicianswho will take their vacations andcontinue to work in a foreign country.”Smith Smith is quick to point out that hefeels he gets more than he gives in hisvolunteer work. “You appreciate what your medical colleagues are doing with minimalresources. You learn from them, because their physical examination skills and theirclinical acumen are so great. We have a lot to offer them with things like TB testing andmalaria vaccination. It’s a true collaborative spirit,” he says. —Maureen PassmoreIn September, Pitt celebrated the 30th anniversary of the emergency medicine residency program.Among those who helped celebrate (from left): Susan Dunmire (MD ’85, Res ’88); Michael Turtorro(Res ’90); Walt Stoy (PhD ’90); Robert Whipkey (MD ’81, Res ’84); Pitt’s academic EM programfounder Ronald Stewart; Dave Ellis (behind Stewart) (MD ’82, Res ’85); former EM departmentchair and the residency program’s first director, Paul Paris (MD ’76); Sandra Schneider (MD ’75,Res ’78); Kevin O’Toole (behind Schneider) (MD ’83, Res ’86); Mike Plewa (Res ’88); Pitt’s currentchair, Donald Yealy (Res ’88); Vince Verdile (Res ’87); and Ronald Roth (MD ’82, Res ’85).When television producers first asked Jen Arnold(Pediatrics Resident ’03, Neonatal/Perinatal Fellow ’07)and her husband, Bill Klein, who both have spondyloepiphysealdysplasia resulting in short stature, to star intheir own reality show, the couple was skeptical. Thensomething happened while she was out shopping. “A littlegirl came up to me and said, ‘You’rea little person like in Little People, BigWorld,’” (another reality show) Arnoldrecalls. In the past, children had oftenpointed or used derogatory terms. Theexperience helped her see the educationalpossibilities. Says Arnold, “I’vealways been happy to share awareness.”Now entering its fifth season,The Little Couple follows Arnold andKlein through their daily lives, fromsearching for a home to consideringtheir options for starting a family.at Texas Children’s Hospital in Houston, where she’sa neonatologist and medical director of the PediatricSimulation Center, a program she helped build aftertraining at Pitt’s WISER Center.While working at the Mayo Clinic in 2005, AliHendi (Dermatology Resident ’03, Mohs MicrographicSurgery Fellow ’04) noticed a gapin medical literature. As a skin cancerspecialist and Mohs surgeon,Hendi often received referrals fromgeneral practitioners for lesionsthat mimicked skin cancer but werenot. “There was really no atlas ofskin cancers geared toward primarycare physicians,” he recalls. It alsooccurred to him that he had accessto high-quality images of everytumor treated at the Mayo Clinic,which “were not being utilized toThe show also depicts Arnold’s work Hendi’s 2011 booktheir maximum potential.” So withJuan-Carlos Martinez, Hendi wroteAtlas of Skin Cancers, Practical Guide to Diagnosis andTreatment (Springer, 2011), which details skin cancersin their many forms, as well as conditions that commonlymimic them.Jill Hagenkord (Pathology/Oncology InformaticsFellow ’07, Molecular Genetic Pathology Fellow ’08)recalls facing criticism for how she saw the future ofmedicine before she came to Pitt. Genomic technologieswere too expensive—totally impractical for clinical use,her instructors told her. That changed when she beganher training in informatics and molecular genetic pathologyhere. The directors of these programs—MichaelBecich and Jeffrey Kant, respectively—had each “definedtheir fields,” she says. “To have access to these twopioneering guides who actually got what I wanted todo was amazing.” Hagenkord, who was recently namedchief medical officer of Complete Genomics, a humangenome-sequencingservice company, hopes to continueher mentors’ tradition of innovation. “Whole genomesequencing as a diagnostic tool breaks the mold in somany ways. It’s really utterly game changing.”—Jessica Titler and Elaine VitoneWINTER 2011⁄12 37

ELSIE R. BROUSSARDJAN. 30, 1924–SEPT. 12, 2011As a pediatrician in the late 1950s, ElsieBroussard noticed that when mothersbrought infants in for their well-babyvisits, they brought a range of perceptionsto the exam table. “Some mothers would seetheir babies in a positive light—active, energetic—while otherswould describe [babies who werejust as active] as out-of-control difficult,”explains Broussard’s daughter,Jude Cassidy, a PhD professorof psychology at the University ofBroussard Maryland. Curious as to how thoseperceptions would influence theirparenting—and in turn, their children’s development—Broussardpursued a master’s and aPhD in maternal and child health at Pitt. Inthe ensuing decades, she helped legitimize thenewly emerging field of infant mental health asher hunches about the roots of mental healthin parent-child relationships bore out.In September, Broussard, professor emeritusof public health psychiatry and clinicalassociate professor of psychiatry in the Schoolof Medicine, died of a heart attack while drivingin Shadyside. She was 87.In 1963 Broussard launched a longitudinalstudy called the Pittsburgh First-Born Project,and for nearly 40 years, Broussard workedwith families to determine what stood inthe way of positive parenting behaviors anddeveloped interventions that proved successfulin improving children’s outcomes. RecallsBroussard’s son, Francis Cassidy (MD ’79),“She told us many times you can never spoila baby. You can never love them too much.”—Elaine VitoneBERNARD I. MICHAELSDEC. 26, 1917–JULY 22, 2011There are few people who can claim toenjoy going to work every single day.Bernard I. Michaels (MD ’42, Res’48), clinical professor of pediatrics at Pittand former president of the medical staff atChildren’s Hospital of Pittsburgh of UPMC,who practiced there for almost 60 years,was one of those rare people, says his son,Robert Michaels. “He loved being helpful,liked making a difference in the well-being offamilies, and adored watching children growup.” The elder Michaelscared for many of hispatients from birth intoadulthood and manyfamilies through multiplegenerations. He alsotook pride in the “hugeMichaelsnumber of patients ofhis who became pediatricians,”adds Robert Michaels, who pursuedthe same path himself.Bernard Michaels died of a heart attack inJuly. He was 93.When Children’s Hospital of Pittsburgh ofUPMC installed a historical timeline muralin its new location two years ago, Michaelswas one of the few physicians to be includedin the painting, notes Andrew Urbach, medicaldirector for clinical excellence and service.“He had a passion for pediatrics and forhis families,” Urbach explained. “He hada level of excellence that set a standard forPittsburgh.” —Jessica TitlerFÉLICIEN M. STEICHENOCT. 13, 1926–JUNE 27, 2011Since Félicien Steichen, professor emeritusof surgery at New York MedicalCollege, died in June, it’s been difficultbreaking the news to his mentees, sayslong-time colleague Jean-MichelLoubeau (Res ’77). One said hefelt like he’d just lost a secondfather. Steichen was known tojoin his residents on call even lateinto the night. “He always said,We have to teach these young peoplenot how to do an operation but Steichen with hishow to operate,” Loubeau recalls, grandson Adrien.adding that many of Steichen’spupils went into academic surgery.Steichen was professor of surgery at Pittand associate chief of surgery under MarkRavitch at UPMC Montefiore in the 1970s.Together, they developed a course in surgicalstapling at Pitt, instructing hundreds ofsurgeons from all over the world on “how tooperate” as a new surgical paradigm emerged.Ravitch and Steichen worked with U.S.Surgical Corporation to create these instruments,as well as several of the first miniaturizedstaplers, trocars, and other devices thatushered in the era of minimally invasive surgery.Ever wary of a conflict of interest, theydid all their consulting gratis.Years ago, Steichen’s son, François Steichen,happened to meet one of his father’s trainees.The younger Steichen was at an appointmentfor an insurance physical when the doctorrealized François was his mentor’s son andsheepishly offered a hug, recalls François.“I told him, ‘Yes, it’s okay. I’ve heard thisbefore.’” —EVIN MEMORIAM’40sTHOMAS R. SARACCOMD ’43AJULY 19, 2011CONSTANTINE Z.MORAITISMD ’47OCT. 10, 2011’50sMELVIN L. COHENMD ’53SEPT. 4, 2011GEARY EICHER JR.MD ’54SEPT. 10, 2011MICHAEL LADOMD ’55AUG. 11, 2011JOSEPH TANNENHAUSRES ’56MAY 24, 2011STEPHEN A. STEVENSMD ’58JULY 15, 2011RICHARD DIETRICKMD ’59AUG. 6, 2011ROBERT G. O’BRIENMD ’59JUNE 3, 2011NICHOLAS N.VASILOPOULOSMD ’59AUG. 19, 2011’60sJOHN L. MINARDMD ’61AUG. 20, 2011THEODORE M.TABACHNICKMD ’61SEPT. 2, 2011’70sJUDITH E. ORIEMD ’78NOV. 5, 2011FACULTY/STAFFGEORGE THIERSJUNE 9, 201138 PITTMED

JULIE MAGARIANBLANDERIMAGINES A NEW KINDOF VACCINEBY KRISTEN COSBYWhen the American embassy in Lebanonwas bombed in 1983, the immigrationpaperwork of Julie Magarian Blander’sfamily went up in flames—along with theirchances of escaping the civil war that had beenraging since 1975.Blander was 9 when the war began. “You’dbe in school, and all of a sudden, there wouldbe bombs falling,” she says. “You would have tobe picked up under great danger.”By the time her family was able to escapeto the United States, she was a year awayfrom completing her bachelor’s degree at theAmerican University of Beirut. She made thedecision to see it through and keep her scholarship—shewas used to living in danger, she says.Now, Blander (PhD ’97) faces grave threatsof a different sort—deadly microbes—as anassociate professor of immunology and directorof the Innate Immunity Research Program atMount Sinai in New York City. In July, Blanderreceived the 2011 Burroughs Wellcome FundAward in Pathogenesis of Infectious Diseases.As a postdoc at Yale, she worked with thelate Charles Janeway Jr., a founder in the fieldof innate immunology. He’d put forth the“far-fetched” proposal that the cells that makeup our immune systems have receptors thatcan tell the difference between cells that makeup our own tissues and the cells of foreigninfectious agents; therefore, there must beGRAHAM JOHNSTONE (MD ’70)PresidentBRIAN KLATT (MD ’97)President-electMARGARET LARKINS-PETTIGREW (MD ’94)SecretaryPETER FERSON (MD ’73)TreasurerROBERT E. LEE (MD ’56)HistorianSUSAN DUNMIRE (MD ’85)Executive DirectorMEDICAL ALUMNIASSOCIATION OFFICERSFRANK HARRISMagarian Blander solvedthe mystery of whyvaccines based on livebacteria outperform theirkilled-pathogen counterparts.identifiable structures on foreign microbialcells that provoke our immune system toreact. When Blander joined Janeway’s lab in1997, he and postdoc Ruslan Medzhitov hadjust confirmed the existence of such a mammaliancell receptor.Blander was eager to learn more about theimmune system—in particular, why vaccinesmade of living, attenuated strains of a pathogenare more effective than vaccines made ofdead pathogens. She proposed her own farfetchedhypothesis: Not only can our immunesystems tell the difference between our owncells and foreign cells, but also between livingforeign cells and dead foreign cells.Blander studied immune-cell reactions tolive bacteria and found that the immune cells’receptors responded to a certain kind of messengerRNA molecule that is structured verydifferently from our own messenger RNA molecules.But when the invading bacterial cellsDONALD MRVOS (MD ’55)CARL ROBERT FUHRMAN (MD ’79)GREGORY M. HOYSON (MD ’82)JAN MADISON (MD ’85)JOHN F. MAHONEY (MD ’90)VAISHALI DIXIT SCHUCHERT (MD ’94)ADAM GORDON (MD ’95)CHARISSA B. PACELLA (MD ’98)HEATHER HEINRICHS WALKER (MD ’99)BRETT PERRICELLI (MD ’02)Members at LargeM-200k Scaife HallUniversity of PittsburghPittsburgh, PA 15261tel 412-648-9090; fax 412-648-9500medalum@medschool.pitt.edudied, their load of RNA molecules was rapidlylost. The messenger RNA molecules served assignatures of microbial viability. They weremissing from dead vaccines, hence the weakerimmune response to them, and adding themback augmented dead vaccines to perform aswell as live vaccines. Blander’s findings werepublished in Nature in May 2011.Blander imagines that in the future we willbe able to take molecules made from deadpathogens and supplement them with thesesignature molecules. “So you can combine thebest of both—what’s good in a live vaccine andin a dead vaccine—and it’s safe,” says Blander.“You can vaccinate people without having thefear of being injected with a viable strain ofmicroorganism.”If Blander is successful in synthesizingthese signature molecules, her efforts couldlead to the creation of a universal vaccine, onethat could be adapted to fight any microorganism—oreven tumor cells, she says. (Herresearch applies only to bacteria, yet she is confidentthat similar signature molecules indicativeof microbial viability will be found inviruses, parasites, and fungal infections, too.)Such a vaccine would greatly reduce the timeit takes to launch immunization efforts againstnew microbial contagions. It would also makeit easier to vaccinate populations in disasterzones and developing nations, where it is difficultto administer the multiple doses deadvaccines require.“It seems like a simple idea,” she says, “butit has tremendous implications for the developmentof vaccines for infectious disease, oreven for cancer immunotherapy.” WINTER 2011⁄12 39

LAST CALLSTOLEN MOMENTSLiving within gurney-rolling distance of the Schoolof Medicine is “addictively convenient,” saysSarah Ramer (Class of ’12), who has lived at theUniversity of Pittsburgh’s Darragh Street Apartments,located just two blocks from Scaife Hall,since the complex opened in 2007.There’s the sense of community one wouldexpect when med students share walls. Ad-hocstudy groups. Walking next door in socks to borrowsugar to make cookies for a potluck. Impromptucornhole tournaments on Darragh’s courtyard (ahot spot for student group functions, as well aspersonal gatherings). Benjamin Cobb (Class of ’13)says he first met many of his classmates at a partyin the courtyard. A year later, after the constructionof a new patio, he recalls, “During the summer, meand my friends would get together on the patio,grill some stuff, and just chill out on the grass andeat burgers.”Darragh has, quite literally, optimally positionedCobb to get the most of his evenings. Hehas been known to stop by when he sees a professor’slight on in Scaife after hours. Stolen momentswith busy profs can be hard to come by otherwise.And, Cobb says, “Sometimes, after I leavethe hospital, I’ll throw some regular clothes on,walk across the street to the hospital, and see mypatients.” He recalls one patient who was flat andunresponsive during his rotation; she brightenedup at night when her family was able to visit.“At night, I can sit down and talk to them. Andwhen I’m done, just go right across the street andgo back to sleep.” —Jessica Titler—Photography by Cami MesaRamer (top) and Cobb.40 PITTMED

C A L E N D A ROF SPECIAL INTEREST TO ALUMNI AND FRIENDSMEDICAL ALUMNIWEEKEND 2012MAY 18 –21, 2012Reunion Classes:2002 19971992 19871982 19771972 19671962 1957For information:medalum@medschool.pitt.edu.Or go to www.maa.pitt.edu.ERIE HEALTH SCIENCESALUMNI RECEPTIONDECEMBER 66 p.m.Courtyard by MarriottAmbassador Conference CenterGarden AtriumErie, Pa.For information:Pat Carver412-647-5307cpat@pitt.eduCLEVELAND HEALTHSCIENCES ALUMNIRECEPTIONDECEMBER 86 p.m.MYXX RestaurantFairmount Business DistrictCleveland HeightsCleveland, OhioFor information:Pat Carver412-647-5307cpat@pitt.eduWEST PALM BEACHHEALTH SCIENCESALUMNI RECEPTIONFEBRUARY 156 p.m.Esperante Corporate Center, AtriumWest Palm Beach, Fla.For information:Pat Carver412-647-5307cpat@pitt.eduNAPLES2012 WINTER ACADEMYFEBRUARY 17Ritz-CarltonNaples, Fla.For information:Pat Carver412-647-5307cpat@pitt.eduwww.winteracademy.pitt.eduUPCOMINGHEALTH SCIENCESALUMNI RECEPTIONS:DATES TBALos Angeles, Calif.Phoenix, Ariz.San Francisco, Calif.For information:Pat Carver412-647-5307cpat@pitt.eduTO FIND OUT WHAT ELSE IS HAPPENING AT THE MEDICAL SCHOOL, GO TO www.health.pitt.edu

UNIVERSITY OF PITTSBURGHSCHOOL OF MEDICINESUITE 401 SCAIFE HALLPITTSBURGH, PA 15261CHANGE SERVICE REQUESTEDDON’T PLAY THE GOATCOME BACK FOR REUNIONBilly, here, and his white-clad friend were best buddies atthe School of Medicine in the mid-1930s, but they lost touch.Never attended any of their Pitt med reunions—don’t thatbleat all?Don’t mutton to yourself over missed opportunities. Taketime—Friday, May 18 to Monday, May 21, 2012—to reconnectwith the people and places that made your medical educationspecial. It’ll be fun.Classes whose years end in 2 and 7 will be recognizedthroughout the weekend. Figuring out if your cohort is one isso easy a kid can do it. (Or you can just look at the calendarlist on the other side of this cover.)So goat for it, and join your classmates at Medical AlumniWeekend 2012.Register at www.maa.pitt.edu/reunionweekend/PHOTO COURTESY FAMILY OF EDWARD J. CARROLL JR. (MD ’34)