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Dartmouth Medicine 3Summer 2003

It’s not unusual that the newlyappointed dean of DartmouthMedical School is a pediatri-cian—15 current medical schooldeans trained in pediatrics, morethan in any other specialty ex-cept internal medicine. But whatis unusual is that the new deanalso holds a doctorate in phar-macology and is coming to DMSfrom industry rather than—atleast directly—from anothermedical school.

Succeeds: On July 1, StephenSpielberg, M.D., Ph.D., becomesdean of DMS as well as vice pres-ident for health affairs of Dart-mouth College and a professor ofpediatrics and of pharmacologyand toxicology. He succeedsJohn Baldwin, M.D., who wasdean from 1998 to 2002, andEthan Dmitrovsky, M.D., who ischair of pharmacology and toxi-cology and served as acting deanduring 2002-03.

Since 1997, Spielberg hasbeen vice president for pediatricdrug development at Johnson &Johnson’s Pharmaceutical Re-search and Development branchin New Jersey. There, he oversawthe development of more effec-tive labeling of children’s medi-cines as well as of new approach-es to conducting clinical inves-tigations in the pediatric popu-lation. From 1992 to 1997, hewas executive director of ex-ploratory biochemical toxicolo-gy and clinical and regulatorydevelopment at Merck.

He has long been an advocate

for children’s health and ledpharmaceutical industry advoca-cy in Congress for the Best Phar-maceuticals for Children Act,which was signed into law in2002. He has also led industry ef-forts to foster investigation ofnew medicines in pediatric pop-ulations; organized internation-al efforts to harmonize children’sdrug development regulations;and helped initiate U.S. and in-ternational efforts to assure thehighest ethical standards in pe-diatric clinical investigations.

Spielberg also has consider-able experience in academicmedicine. He was at Johns Hop-kins from 1977 to 1981 and atthe University of Toronto and itsHospital for Sick Children from1981 to 1992. Even while work-ing in industry, he has kept histies to academe—as an adjunctprofessor at Jefferson MedicalCollege in Philadelphia and atRobert Wood Johnson MedicalSchool in New Jersey.

Perspective: Having worked inindustry gives Spielberg a per-spective not afforded manyphysicians. Overseeing clinicaltrials, for instance, means thathe’s traveled to medical schoolsall over the world. He thus rec-ognizes that “one of the majorgaps that we’re facing, both inthe United States as well as in-ternationally, is a dearth of well-trained clinical investigators andtranslational scientists. We areoften faced with a situationwhere we have a great new ad-vance in therapeutics . . . [but]we can’t even find investigatorsto properly carry out studies.”Medical schools must recognizethat the “translation of science

DMS’s new dean is a pediatrician anda pharmacologist

F A C T S & F I G U R E S

“If you think research is expensive, try disease.”— Philanthropist Mary Lasker (1901–1994)

The cost of disease . . .Annual direct and indirect costs for just a few diseases,

as estimated by the National Institutes of Health

Mental Disorders

$148 billion

Heart Disease

$128 billion

Alzheimer’s Disease

$100 billion

. . . and of the search for curesAnnual funding for biomedical research in 2002

Extramural funding nationwide from the National Institutes of Health

$19 billion

External grants and contracts income to DMS

$111 million

4 Dartmouth Medicine Summer 2003

into good clinical investigation,and, in turn, into clinical care, isa vital issue,” he says.

Spielberg also appreciates thevalue of collaboration—an areawhere Dartmouth is alreadystrong—in translating biomed-ical research discoveries into pa-tient care. He believes that hisindustry experience “fosteringthe development of interactionsamong people with very diversebackgrounds and interests willserve very well in a medicalschool context. Industry is set upin such a way as to cut across dis-ciplines, to cut across traditionalsilos between basic and clinicalinvestigators.”

Attitude: Ensuring that scien-tific discoveries have an “impactin real-time patient care,” saysSpielberg, “requires a very differ-ent attitude towards medicineand a very different attitude to-wards working together—basicscientists with clinicians; clini-cians with their patients in thecontext of a community—tomake sure that those advancesreally do impact the well-beingof the people.”

He is pleased that transla-tional research is already beingemphasized at Dartmouth. In hisnew role as dean, Spielberg in-tends to “maintain the excel-lence that already exists in thebasic sciences, . . . expand onwhat already is a very successfulNIH-funding rate, and look foradditional sources of funding tosupport basic science,” while alsocontinuing to advance transla-tional and clinical research and“building even further on thingssuch as the Center for EvaluativeClinical Sciences, which looks

at outcomes in largerpopulations.”

Happiness: He’s im-pressed that “there is alevel of happiness [atDMS] that I don’tthink you find in mostmedical schools thesedays. It’s a real phe-nomenon,” he says. Heattributes it to people’sfeeling a “sense of bothindividual worth and ofcommon purpose.”

And he’s impressedby the quality of DMS’scurriculum. “I want toassure that the qualityof education which al-ready exists is going onin a milieu of active in-vestigation—basic,translational, clinical,and evaluative—and inan atmosphere wherepeople truly believe inwhat they’re doing and are hav-ing fun doing it,” he says. “Be-cause that, in fact, is going toproduce the next generation ofphysicians who are going to leadin medicine.

“As a pharmacologist,” headds, “I’m particularly impressedby the way therapeutics is taught[at DMS].”

During a visit to campus inMay, he had a chance to meetsome DMS students. He saysthat he was delighted by the“wonderfully open and frankquestions” they asked him, andthat—as a longtime member of achoral group—he was pleased tohear about the student a cappellagroup, the DMS Dermatones.

Spielberg earned his A.B.from Princeton and his M.D. and

Ph.D. in pharmacology from theUniversity of Chicago. Hetrained at Children’s Hospital inBoston and at the National In-stitute of Child Health and Hu-man Development.

He is a member of the Feder-al Advisory Committee for theNational Children’s Study, theboard of the Foundation for theNational Institutes of Health,the Institute of Medicine Panelon Ethics in Pediatric ClinicalTrials, the FDA Pediatric Advi-sory Subcommittee, and the sci-entific advisory board of the Eliz-abeth Glaser Pediatric ResearchNetwork.

Spielberg looks forward tomoving with his family toHanover. His wife, Laurel Spiel-berg, M.P.H., Dr.P.H., has

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w o r k e d i n p u b l i chealth in the U.S. andCanada and most re-cently was an associateprofessor of epidemiol-ogy at Drexel. She willwork part-time—doingresearch and teaching—in Dartmouth’s De-partment of Communi-ty and Family Medi-cine. They have twosons: David, 20, asophomore at Prince-ton; and Jeff, 15, asophomore at HanoverHigh School.

Critical time: “This isreally a very criticaltime in the history ofAmerican medicine,”says Spielberg, “a timewhen we really need tothink strongly abouteducational issues,about research, about

how great institutions contributeto their communities.”

He was attracted by the factthat at Dartmouth, there’s “a realdedication to looking at howhealth care impacts a communi-ty. Medicine [must be] very inte-grated and very collegial, andneeds to be oriented towards acommunity of care. The nidus ofthese things exists here, at leastin part because of scale, location,but mostly because of people.The kinds of people who have avision of what medical school,medical education, research, andhealth care should be.”

He’s here, he adds, becausethe “opportunity to participatein that process and be a leader inthat process was irresistible.”

Laura Stephenson Carter

DMS’s new dean, pediatrician and pharmacologist StephenSpielberg, is animated about the opportunity ahead of him.

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1989. He heads UCI’s Divisionof Endocrinology, Diabetes andMetabolism and its diabetes andosteoporosis programs.

Nationally known for his re-search on the molecular under-pinnings of pancreatic cancer—one of the five deadliest cancersin the U.S.—Korc explores dis-ruptions in cell signaling path-ways caused by growth-stimulat-ing factors. He also studies themechanisms of peptide hor-mones and diabetes mellitus.

His interest in endocrine-ex-ocrine interactions in the pan-creas grew out of his postdoctor-al work in the late 1970s at UC-San Francisco, where he studiedphysiology, cell biology, andmolecular biology.

Relevance: He wanted his workto have clinical relevance, too.He was particularly interestedthat people with type II diabetesmellitus have a higher incidenceof pancreatic cancer. So he com-bined his clinical and researchinterests into a lifelong study ofpancreatic cancer.

His early research focused onepidermal growth-factor recep-tors in pancreatic cancer.Growth factors are moleculesthat stimulate cell growth; re-ceptors, on the cell surface, bindspecific molecules outside thecell. In the 1980s, Korc proposedthat mitogenic signaling (signalsfor cells to divide and grow) isenhanced in pancreatic cancercells. He found that human pan-creatic cancers overexpress manygrowth factors—and their asso-ciated receptors—which, inturn, overactivate the mitogenicpathways. “These alterations areakin to a car going out of control

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“I found it exhilarating to con-sider working in one of the bestdesigned hospitals in the U.S. asa member of a Department ofMedicine that is strong and vi-brant and blessed with superbclinicians, educators, and re-searchers,” says distinguished en-docrinologist and cancer biolo-gist Murray Korc, M.D.

Chair: Korc, who will becomechair of medicine at DMS onSeptember 1, succeeds HaroldSox, M.D., both as the head ofthe department and as theJoseph M. Huber Professor ofMedicine. Donald St. Germain,M.D., has been the department’sacting chair since Sox left in July2001 to become editor of the An-nals of Internal Medicine.

Korc has been a member ofthe faculty at the University ofCalifornia at Irvine (UCI) since

Endocrinologistfrom UC-Irvineto head medicine

This cane isn’t candy, but it is sweet

F or Radford Tanzer, M.D., holding Hanover’s Boston PostCane “feels pretty good,” according to the 97-year-old pro-

fessor emeritus of plastic surgery.Tanzer, as the oldest citizen of Hanover, is the bearer of the

town’s historic Boston Post cane—one of 700 original canes thatdate back to 1909. Made of Gaboon ebony from Africa, the el-egant walking stick has 14-carat gold sheeting wrapped aroundits top and is inscribed: “Presented by the Boston Post to theoldest citizen of Hanover.” Tanzer has his own theory about afew small dents in the cane’s top. “It has been used for crackingnuts,” he surmises.

Edwin Grozier, publisher of the Boston Post newspaper, start-ed the tradition in 1909 when he had the canes manufacturedand distributed to 700 towns in New England, requesting thatthey be presented to the town’s oldest male citizen. When thatindividual died, the cane was to be passed on to the next old-est male in town. It was not until 1930, after considerable pres-sure, that women were officially eligible for the honor.

The cane was presented to Tanzer by Brian Walsh, head ofthe town’s Selectboard, to a standing ovation last spring. Theceremony took place at a special service at St. Thomas Episco-pal Church, where Tanzer has been a member since 1921, whenhe was a freshman at Dartmouth College.

After joining the DMS faculty in 1939, Tanzer achieved in-ternational renown as the “Father of Ear Surgery,” for his de-velopment of the standard technique for total ear reconstruc-tion. He retired in 1970, and in 1991 the plastic surgery suiteat DHMC was named in his honor. M.C.W.

Sadly, Rad Tanzer died on June 12, after a brief illness, just as thisissue of the magazine was about to go to press.

Radford Tanzer, an internationally known plastic surgeon and long-time member of the DMS faculty, holds Hanover’s Boston Post cane.

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Murray Korc is coming from UC-Irvineto chair medicine at Dartmouth.


with the accelerator stuck to thefloor,” he says.

Later, he found the signalingabnormalities were due to de-fects in growth-inhibiting regu-lators. Using the car analogyagain, he says it’s like a brokenbrake. And further discoveriessuggested that “not only is thebrake broken, but it has turnedinto a second accelerator.” Even-tually, these findings may lead to“novel therapeutic strategies forthis deadly disease.”

Korc is a past president of theAmerican Pancreas Association,well-funded by the National In-stitutes of Health, and the au-thor of more than 200 publica-tions. He serves on the editorialboards of several journals, in-cluding Pancreas and the Journalof Biological Chemistry. He previ-ously held posts at the Universi-ty of Arizona and UC-San Fran-cisco, after receiving his M.D.(1974) and training (1974-1977)at Albany Medical College.

Collaborations: At DMS, Korcsays, “I hope to move the De-partment of Medicine forward ina collegial manner that respectsthe accomplishments, goals, andaspirations, as well as the con-cerns, of the clinicians, clini-cian-scientists, and administra-tors . . . in an environment thatfosters intra- and interdepart-mental collaborations.” He is astrong believer in “excellence inscholarly activity in order . . . toexcel in education, patient care,and service.”

Korc is married to AntoinetteKorc, M.D., and they have threechildren—Paul, 23; Melissa, 19;and Ashton, 15.


Henriksen had met William-son at conferences and knew ofhis research on frontal lobe epi-lepsy, so he asked Williamson tosee Sibbern. When she arrived atDHMC, Williamson and histeam administered many tests.The results of both the MRI andEEG were normal, but from herhistory Williamson’s team wassure Henriksen’s diagnosis wascorrect. The trick was to pin-point the seizures’ source.

The team then did SPECT(single-photon emission com-puterized tomography) scans, aneuroimaging technique thatmeasures blood flow, which canindicate where seizures begin.The SPECT scan showing thearea of the seizure is then corre-lated with an MRI (since the res-olution of an MRI is much moredetailed), to see precisely wherethe seizures originate. In Sib-bern’s case, they came from deepin her frontal lobe—above herright eye, straight back, towardthe middle of her brain.

By placing electrodes on and

in Sibbern’s head—some on thesurface and some deep in herbrain—and taking a series of dai-ly recordings, the team was ableto pinpoint the exact spot wherethe seizures began. DHMC neu-rosurgeon David Roberts, M.D.,could then surgically removethat area. “We found abnormaltissue right at the [spot] that wasmost active for causing theseizures,” says Roberts. “She hada condition called cortical dys-plasia; that’s just a little area ofthe brain that when it devel-oped, developed abnormally.”

Since the operation, Sibbernhas had no seizures. “She wasamazing. She was up and at ’emvery quickly,” says Roberts.“Apart from being a little tired,. . . she didn’t turn a hair.”

Team: It was a team effort thattransformed Sibbern’s life. TheDHMC Epilepsy Program reliesheavily on the collaboration ofmany people: neurologists, aneurosurgeon, a nurse coordina-tor, nurses, neuropsychologists,psychiatrists, radiologists, andelectrodiagnostic technicians.“We’re a good team, and we be-lieve that everyone deserves achance,” says nurse coordinatorKaren Gilbert, A.R.N.P.

Back in Norway, Sibbern isadjusting to her new life. Shenow enjoys spending time out-doors with her husband and herdaughters. She may even returnto work. “If I still keep seizure-free, I will have possibilities to doa lot more than earlier,” she says.“But I think I have not quite gotused to my new situation yet. Fora while I will just think abouthow to live for the future.”

Matthew C. Wiencke

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After suffering from seizures foralmost 50 years, Eva Sibbern isfinally able to do what she enjoysmost in life—spend time withher family, ride horses, and gocross-country skiing—all seizure-free, thanks to DHMC’s Epilep-sy Program.

Sibbern, a native of Oslo,Norway, started having seizuresat age six. They were fairly wellcontrolled for many years, oc-curring only once or twice amonth. She graduated from theUniversity of Oslo Law School,married, and raised two daugh-ters. But when she reached herforties, the seizures became moresevere—so much so that she wasafraid to go out in public and hadto take a leave of absence fromher job as deputy director of Nor-way’s Ministry of Education, Re-search, and Church Affairs.

Sibbern sought help from Dr.Olav Henriksen, a top epilepsyspecialist in Norway. Henriksendiagnosed Sibbern as havingfrontal lobe complex partialseizures—a type of seizure thataffects only about 20% of epilep-sy patients. Through medication,Sibbern was able to limit herseizures to the evening hours, butshe still had six to eight a night.

Bizarre: “They are very bizarreseizures, where Eva would wakeup out of sleep and start scream-ing and shrieking,” explains Pe-ter Williamson, M.D., director ofthe Epilepsy Program at DHMC.“It looks like a panic attack butit really indeed is epilepsy.”

Trip from Norwayends a lifetime ofcoping with seizures

Eva Sibbern, left—pictured here withher daughters Christin, rear, and Maria—is now back in Norway, seizure-free.


east, to stay close to her family.“Brought the cell phone withme,” she added, so she couldshare the news right away.

At 12:00 noon, a loud whistlecaught everyone’s attention asAssistant Dean Susan Harper,M.D., and Acting Dean EthanDmitrovsky, M.D., arrived withthe tall stack of envelopes.Dmitrovsky opened the ceremo-ny by congratulating the ’03s andpraising their hard work. Thenwithout further ado he an-nounced, to cheers and applause,“Let’s get on with it!” Harper, en-velopes in hand, told the stu-dents, “You will be very pleasedwith the results.”

Thrilled: As each name wasread, to bursts of applause andraucous comments, the studentsapproached Harper to get theirenvelopes—and a handshake ora hug. Some waited until the cer-emony was over to open theirenvelopes, but others, like ToddBarr, could not contain their ex-citement. Barr pulled out his let-ter right away, paused a moment,then shouted “Dartmouth!” ashe waved it above his head. “Iopened the envelope,” he ex-plained afterwards, “and it took along time to see the fine print,and then—wow, there it was! Ifeel like I’ve won the AcademyAward.” Paige Wickner wasthrilled, too, by her acceptanceat Brown.

Three pairs of ’03s—includ-ing Steven Xanthopoulos andAmy Vinther—entered theMatch as a couple. They wereamong 575 participants nation-wide in the couples portion ofthe National Resident MatchingProgram (NRMP), a new record.

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For the members of the DMSClass of ’03, four years of classesand exams boiled down to oneday, one moment, one white en-velope. The day was Match Day,March 20, 2003, and the mo-ment shortly before noon. Excit-ed ’03s gathered with their fam-ilies, friends, and faculty mem-bers inside DHMC’s AuditoriumG, waiting to receive life-defin-ing white envelopes containingword of the hospitals where theywould train as residents.

By 11:55 a.m., the room res-onated with the anxious chatterand laughter of students, babiesin strollers, and well-wishers car-rying balloons and bouquets offlowers.

“It’s wild. It’s hard to believewe’re here. The last few dayshave been very busy—lots ofpresentations and finishing upclasses,” said Todd Barr, a fourth-year student who worked as aflight attendant for U.S. Airwaysfor 10 years before enrolling atDMS. He had applied to resi-dency programs in psychiatry allover the country, listing DHMCas his first choice. “I own a housein the Upper Valley,” he said,“and would like to stay in thecommunity.”

Eager: The students were eagerto open their envelopes, ready toaccept whatever word was inside.“I just want to have it over with,”said Paige Wickner. “I don’tmind so much where I go.” Shehad applied to general internalmedicine programs in the North-

Soon-to-be M.D.’sgather together tomeet their matches

The emotions of Match Day ranged from1 tension (for Michael Bartholomew, ashe got his envelope from Susan Harper)to 2 quiet satisfaction (for David Gib-bons and his family), to 3 jubilation (forTodd Barr), to 4 congratulations (forVanessa Vidal and Leslianne Yen), to 5indulgence, in a cake decorated with theDMS seal and the name of every ’03.

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“It was nerve-racking having noidea going in where we would begoing,” Xanthopoulos said. Butboth were elated by their accep-tance, after a preliminary year,into programs at UCLA—he inanesthesiology and she in emer-gency medicine.

Of the 60 DMS ’03s, 55 par-ticipated in the NRMP; threeentered military programs; onewill do residency at a hospital inCanada; and one obtained anearly Match. Almost half are en-tering primary care specialties—internal medicine (15 students),pediatrics (8), or family medi-cine (4). The graduates will trav-el to 18 different states, thoughalmost half are headed for Cali-fornia (10 students), Massachu-setts (9), or New York (8). TheDMS and Brown-Dartmouthgraduates’ residency assignmentsare listed in the adjacent box.

Crucial: It was a crucial day forthe directors of DHMC’s resi-dency programs as well, for it ison Match Day that they find outwho will join their ranks. (Theincoming residents are listed onpage 9.) According to H. WorthParker, M.D., director of gradu-ate medical education, all pro-grams were very pleased with thisyear’s results. All but one filledtheir positions completely in theMatch, and that one has sincefilled its remaining position. In-ternal medicine, psychiatry, pe-diatrics, obstetrics, and generalsurgery did especially well.

“It will be a hard year to top,”said Parker. “All programs haveexpressed strong enthusiasm fortheir results and the new train-ing year.”

Matthew C. Wiencke

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Outgoing GraduatesThe DMS ’03s who are doing residencies next year, andthe programs that they will be going into, are:AnesthesiologyAdrienne Williams, Dartmouth-Hitchcock

Med CtrEmergency MedicineDerek Barclay, Brigham & Women’s Hosp

(Harvard)Family PracticeRustan Adcock, Mountain Area Health Ed Ctr

(U of North Carolina)Sharon Johnston, McGill UAmy Madden, Maine-Dartmouth Family

PracticeTimothy Pieh, Maine-Dartmouth Family

PracticeInternal MedicineSanjoy Bhattacharya, U of Texas Southwestern

Med Ctr (Dallas)Seth Crockett, Stanford U ProgJohn Dick III, U of Washington Affil HospJonathan Goldstein, Beth Israel Deaconess Med

Ctr (Harvard)Tamas Gonda, New York Presbyterian Hosp

(Cornell)Todd Kerner, Dartmouth-Hitchcock Med CtrJennifer Levy, Virginia Commonwealth U Andy Mengshol, U of Colorado Sara Pietras, Mt Auburn Hosp (Harvard)David Polisner, U of North Carolina Paige Wickner, Brown U ProgLeslianne Yen, U of Washington Affil HospInternal Medicine (Preliminary)Robert Beck, Naval Med Ctr, San DiegoDouglas Franz, U of Arizona Affil HospBruce Fuller, Brown U ProgSara Inati, Lenox Hill Hosp (NYU) Brady McKee, St Vincent Hosp (U of

Massachusetts)Amy Vinther, Martin Luther King, Jr., Med Ctr

(Charles R. Drew U)James Welsh, Dartmouth-Hitchcock Med CtrSteven Xanthopoulos, UCLA-VA Greater Los

Angeles ProgInternal Medicine (Primary Care)Agnes Graves, Cambridge Hosp (Harvard)Adam Hersh, UCSF Med CtrVanessa Vidal, Mt Auburn Hosp (Harvard)Obstetrics-GynecologyLisa Chong, Kaiser Permanente Med Ctr

(Stanford)

Orthopaedics Katherine Bardzik, Hosp for Special Surgery

(Cornell)Daniel Bullock, Dartmouth-Hitchcock Med CtrDavid Gibbons, Med Coll of Wisconsin Affil

HospJason Grassbaugh, Madigan Army Med CtrPathologyTheodore Friedman, William Beaumont Hosp

(Wayne State U)Matthew Leavitt, Stanford U ProgYongping Wang, Hosp of the U of

PennsylvaniaPediatricsLinda Armstrong, Kaiser Permanente Med Ctr

(UCSF)Michael Bartholomew, U of Wisconsin HospElizabeth Bassett, Children’s Hosp of Oakland

(UCSF)David Ciminello, Phoenix Children’s Hosp (U

of Arizona)Katherine O’Donnell, Children’s Hosp of Boston

(Harvard)Jennifer Plant, Children’s Hosp of Oakland

(UCSF)Melissa Woo, New England Med Ctr (Tufts)Pediatrics (Primary Care)Blair Seidler, Mt Sinai Med CtrPlastic SurgeryNilton Medina, Rhode Island Hosp

(Brown)PsychiatryTodd Barr, Dartmouth-Hitchcock Med CtrJennifer Rhodes, NYU RadiologyKara Waters, Maine Med Ctr (U of Vermont)SurgerySarah Greer, Dartmouth-Hitchcock Med CtrJunko Ozao, Mt Sinai Med CtrSurgery (Preliminary)Paul Farris, Dartmouth-Hitchcock Med CtrJason Johnson, U of Minnesota Med SchTransitionalHeidi Becker, Texas Tech U Affil HospAaron Kirkpatrick, William Beaumont Army

Med Ctr Clarence Miao, Harbor-UCLA Med CtrMichael Morris, Good Samaritan Regional Med

Ctr (U of Arizona)Paul Sanchez, John Peter Smith Hosp (U of

Texas Southwestern Med Ctr)UrologyAmy Amend, Albany Med Ctr


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Sarah Conley, Cleveland Clinic Foundation(Case Western Reserve)

This year’s Brown-Dartmouth graduates plan to go intothe following residency programs next year:Family PracticeSaragrace Alvarez, New York Presbyterian Hosp

(Columbia)Katrin Bergeron-Killough, Maine Med Ctr (U

of Vermont)James Lynch, Tripler Army Med CtrBrandi Mendonca, Valley Med Ctr (U of

Washington)Internal MedicineQuang Bui, Hosp of the U of PennsylvaniaAlexander Feller, Yale-New Haven HospInternal Medicine (Preliminary)Rebecca Fisher, St Vincent Hosp (U of

Massachusetts)Erin Hattan, McGill U Terrance Healey, Roger Williams Hosp

(Boston U)Jason McBean, Brown U ProgObstetrics-GynecologyBen Lannon, Beth Israel Deaconess Med Ctr

(Harvard)Ogochukwu Okpala, Brigham & Women’s

Hosp (Harvard)OrthopaedicsMatthew Plante, Rhode Island Hosp (Brown)PsychiatryMichelle Conroy, Butler Hosp (Brown)Surgery (Preliminary)Patricia Ramaley, Brigham & Women’s Hosp

(Harvard)

In addition, these students have already been acceptedinto advanced programs that they will start in 2004:AnesthesiologySteven Xanthopoulos, UCLA Med CtrDermatologyBruce Fuller, Yale-New Haven HospEmergency MedicineAmy Vinther, UCLA Med CtrNeurologyDouglas Franz, U of Arizona Health

Science CtrSara Inati, Columbia Presbyterian

Med CtrRadiologyPaul Farris, Dartmouth-Hitchcock Med CtrBrady McKee, Lahey Clinic (Tufts)James Welsh, U of Arizona Affil Hosp

Incoming ResidentsThe first-year residents entering Dartmouthprograms this summer, and the medicalschools where they received their degrees, are:AnesthesiologyMichelle Parra, U of IowaWilliam Surber, NorthwesternAdrienne Williams, DartmouthFamily Practice (Maine-Dartmouth)Ahmed Aldilaimi, Mustansiriyah Med

Coll (Iraq)Pamela Courtney, U of New England

Coll of Osteopathic MedAmy Madden, DartmouthTimothy Pieh, DartmouthJenny Pisculli, Ben Gurion U (Israel)Gayle Smith, Philadelphia Coll of

Osteopathic MedJan Ryszkowski, American U of the

CaribbeanFerdinant Saran, Beheshti U (Iran)Karen Sokol, U of VermontFamily Practice (New Hampshire-Dartmouth)Kristin Anderson, Marshall UDavid Kehas, TuftsLori Richer, U of UtahMathew Sawyer, U of VermontJon Vore, U of New England Coll of

Osteopathic MedInternal MedicineDavid Alonso, TempleAdam Bernstein, Boston URyan De Lee, LoyolaDuc Do, U of VermontJonathan Duffy, U of Missouri-Kansas

CityKevin Fleming, Case Western ReserveKevin Floyd, Ohio StateRebecca Freitas, U of ConnecticutStephen Grant, U of ColoradoKaren Hartman, U of OklahomaTodd Kerner, DartmouthRandy Loftus, U of IowaSarah McCombs, U of MassachusettsMatthew McDonald, Northeastern

Ohio UDavid Talmadge, U of New MexicoWenshu Yu, U of MassachusettsInternal Medicine (Preliminary)Jeffrey Liou, Nova Southeastern U Coll

of Osteopathic MedDaniel McGinley-Smith, Harvard

James Welsh, DartmouthInternal Medicine (Primary Care)Laura Barre, DartmouthLisa Call, Virginia Commonwealth UAlex Gifford, Pennsylvania StateObstetrics-GynecologySusan Kearing, U of ArizonaLaura McGuire, E Virginia Med SchH. Sidney Mitchell, U of VermontRachel Ware, U of KentuckyOrthopaedicsDaniel Bullock, DartmouthJames Genuario, NorthwesternKarl Koenig, BaylorPathologyScott Dufresne, TuftsTimothy Williams, Flinders U

(Australia)PediatricsAlexis Cirilli, U of WisconsinClare Drebitko, YaleKimberly Gifford, Pennsylvania StateTodd Poret, U of North CarolinaElizabeth Richards, TulaneEric Shamansky, Med Coll of

WisconsinKaren Wright, TemplePsychiatryTodd Barr, DartmouthJason Coles, Michigan StateDavid Crites, U of IllinoisBrent Homoleski, Finch UAndrew Horrigan, Med Coll of OhioWendy Martin, U of MississippiBrian Shiner, Pennsylvania StateEric Ulland, Loma Linda USurgeryJustin Dumouchel, U of PittsburghSarah Greer, DartmouthDavid Hughes, Creighton UDavid Mancini, U of PennsylvaniaSurgery (Preliminary)Melanie Donnelly, U of North DakotaPaul Farris, DartmouthFarsad Khashayar, YaleOscar Ho, U of ArizonaDavid Kelley, Kirksville Coll of

Osteopathic MedStuart Lollis, ColumbiaChristopher Marrocco, Trinity Coll

(Ireland)Jennifer Mitchell, U of AlabamaPeter Steinberg, U of Pennsylvania


risk of the more aggressive ade-nomas by more than 40%.

The national press leapt onthat finding. Although Baron ispleased that the work has beennoticed, he worries that the me-dia may misinterpret the resultsand discourage patients from get-ting regular colon-cancer screen-ings. Though he sees positive as-pects to the publicity, “on theother hand, I’m worried that thepress may get it wrong and endup saying something that will bemisleading for the readers.

“For example,” Baron says, “ifa major newspaper implied thatby taking aspirin someone canforget about colorectal screeningand follow-up, then it’s possiblethe publicity could cause a netharm.” Not only are researchersstill debating the appropriaterole for aspirin in preventativetherapy, he cautions, but patientsshould always consult their ownphysicians before starting or

changing anymedication.

Baron saysthe team hasto conductmore researchin order tou n d e r s t a n dthe geneticmechanismsu n d e r l y i n gt h e e f f e c tshown by therecent study.They plan tofollow its sub-jects to see ifthere are de-layed effects,and they willalso track how

long the positive effects last. Fi-nally, they would like to investi-gate characteristics of the ade-nomas that do occur to look formolecular clues to the develop-ment of colorectal cancer.

Baron and his team want tofind answers to still more ques-tions, but the patients who tookpart in the seven-year study arethrilled with the positive effectsthey’ve experienced so far.

Awareness: “Having been diag-nosed with polyps, I suddenly be-came aware of its implications ina way that I otherwise wouldn’thave been,” explains Janet Mark,a study participant who receivedaspirin and was polyp-free in herfollow-up evaluation. “And, be-cause of that awareness, whenthe option of becoming a partic-ipant in a clinical trial was of-fered, I was pleased to be a par-ticipant. This study will help usall, now and in the future.”

Katrina Mitchell

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Baby aspirin is growing up: It cando more than alleviate pint-sizedaches and pains, a DMS teamhas found. The Dartmouth re-searchers discovered that 81 mil-ligrams of aspirin a day—theequivalent of one baby tablet—can reduce the risk of develop-ing colon adenomas, benign tu-mors that can turn cancerous ifthey’re not removed.

Although other clinical trialshave shown similar findings, theDMS-led nationwide study wasthe first to confirm them in arandomized, double-blind studyof over 1,100 patients with pre-viously diagnosed adenomas.The results of the seven-yearstudy were published in the NewEngland Journal of Medicine.

Neoplasia: “It’s fascinating that‘everyday’ drugs like calcium andaspirin can reduce the risk of co-lorectal neoplasia,” says JohnBaron, M.D., who headed thestudy and also was part of a re-search team that discovered sim-ilar protective benefits from cal-cium supplements.

Interestingly, the researcherslearned that although a baby as-pirin provided a protective ben-efit against adenomas, an adultaspirin—325 milligrams—result-ed in little or no benefit. Ac-cording to Baron, this effect waseven more pronounced for ad-vanced adenomas, which have ahigh tendency to progress tocancer; study participants whotook a baby aspirin reduced theirrate of polyps by 19% and their

A baby aspirina day helps to keepadenomas away

The summer sun makes garden-ers and hikers think about skincancer, but several DMS re-searchers are thinking aboutmelanoma—the deadliest formof skin cancer—year-round.

“Melanoma is a frighteningdisease,” says epidemiologist Lin-da Titus-Ernstoff, Ph.D., whopresented the results of a studyon melanoma risk factors at theMediterranean Melanoma Con-ference in May. “Millimeter bymillimeter, it is a very aggressivehuman tumor. At the presenttime, surgical removal of an ear-ly lesion offers the only certain-ty for a complete cure. To defeatthis disease, we need to focus onpotential causes . . . as well asprevention of precursors and ear-ly melanoma detection.”

Titus-Ernstoff actually dis-agrees with the notion that sunexposure increases the tendencyto develop moles, which can lead

DMS researchers fight melanomaon many fronts

John Baron, seated, leads a research group that recently foundthat a baby aspirin a day may help prevent colon cancer.

Linda Titus-Ernstoff researches risk fac-tors for the deadly cancer melanoma.

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to skin cancer. She cites evi-dence from many studies thatpoint to the true culprits: indi-vidual pigmentation characteris-tics and unusual sensitivity tothe sun. She theorizes that thereis a “constitutional susceptibili-ty” for certain people to developmoles—even if they experiencenormal sun exposure.

Alterations: To understand thispropensity, Titus-Ernstoff has in-vestigated alterations of p16, atumor-suppressor gene that,when it functions normally, pre-vents uncontrolled growth. Sheand a colleague were the first toshow that p16 alterations can oc-cur in benign moles.

They have started analyzingthe risk factors for melanomaand so far have found strong as-sociations between melanomaand atypical moles, as well asmelanoma and benign moles.Until the work is completed, Ti-tus-Ernstoff encourages people topractice self-screening. “My in-terest in the feasibility of self-screening was born years ago,”she says. “At that point, our datashowed that only a minority ofmelanomas were first detected bya physician. Most were first no-ticed by a patient, spouse, friend,or family member.”

Levels: While Titus-Ernstoff islooking at risk factors for mel-anoma, Dartmouth oncologistChristopher Tretter, M.D., is in-vestigating new immunologicaltreatments for the disease. Hav-ing identified improved survivalrates in patients with high levelsof melanoma-specific killer cellsin their blood, Tretter is hopingto discover the key to enhancingthis immune response in all

patients who have melanoma. He is focusing on dendritic

cells, which play a central role inpresenting cancer cells to the im-mune system. “Melanoma is nota passive bystander,” Tretter ex-plains. “It actively suppresses theimmune system. The immunesystem will try to eradicate thetumor, but its response is ineffi-cient because . . . dendritic cellsin a cancer-bearing host are notworking properly.”

Tretter’s work on dendriticcells builds in turn on 20 years ofresearch by immunologist MarcErnstoff, M.D. (who is married toTitus-Ernstoff). Ernstoff has stud-ied how to stimulate immunesystem signalers to enhance theircancer-fighting activity.

Focus: He believes the focus atDartmouth on multiagent ther-apy will help overcome tradi-tional barriers to immunologicaltreatment. “There are places allover the world that are explor-ing these approaches,” he notes,but “only a handful of places[have] the breadth of researchthat focuses on all the differentareas like we do.”

Tretter says DHMC’s growingreputation for novel tumor im-munotherapy is leading to na-tional and international patientreferrals. This fact encourageshim to push on with his research.

“What excites me about thisis being able to think out of thebox in tumor immunotherapy,”Tretter says. “It’s interesting tounderstand how these cells in-teract, and how tumors can in-hibit their function. It is such ayoung field, and there is so muchwe can do in it.”

Katrina Mitchell

“What do you say we play bingo?”

B eing late is not an option for “Bingo Bob.” It’s 1:50 p.m. ona Tuesday, and volunteer Robert Kirk is on his way to the

DHMC production studio. He enters, takes a seat at a long tablecovered with green felt, and hooks up a microphone. A pro-duction assistant says, “Five seconds—stand by.” Kirk turns toface the camera, smiles, and says, “Good afternoon, everyone.It’s two o’clock and time for hospital bingo.”

Kirk—known as Bingo Bob—has hosted a weekly hour-longbingo session at DHMC for 18 years. The game is televised, sopatients all over the Medical Center can play. Bingo cards aredelivered on meal trays, and patients who want to play tunetheir TV to the in-house channel. They follow along as Kirktumbles a wire basket holding numbered bingo balls.

“If you get bingo,” Kirk tells viewers, “give us a ring at 5-4945and we’ll chat. Then at three o’clock we’ll come around with abasket of prizes. . . . Now, what do you say we play bingo?”

The numbers come fast and furious. “Check out the neigh-borhood of N-31,” Kirk says. “How does I-18 look to you?” Heestimates he’s hosted more than 6,500 games of bingo—sevengames an hour, 52 weeks a year, for 18 years. It’s a hard post tofill; the volunteer has to be highly dependable, have a sense ofhumor, enjoy meeting patients, and be comfortable in front ofa camera. “I’ve tried to retire several times, but they won’t letme,” jokes Kirk. But his daughter, Nan Carroll (pictured withhim above), fills in if he’s sick or out of town.

At the end of this hour, there are 15 winners. DHMC’s PinkSmock Gift Shop donates the prizes—such as puzzle books orstuffed animals. Today, a patient in the neuroscience unit is gladto pick some playing cards; she’s a big card player and forgot tobring a deck from home. Meeting the patients is one of the joysof the job. “They look you right in the eye,” says Kirk, “and say,‘God bless you. You’re doing a good thing.’” L.J.W.

“Bingo Bob” Kirk, right, has been a faithful volunteer for 18 years.

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enough money to buy the thingsyou need to live every day, suchas food, clothing, or housing?”and “During the past four weeks,was someone available to helpyou if you needed and wantedhelp?” Aside from entering theirzip code and the name of theirhospital or clinic, respondentsare anonymous.

The survey takes about 10minutes to complete, and thoseneeding assistance or lacking In-ternet access can fill it out at aparticipating health center. Af-ter putting in their answers, pa-tients receive a computer-gener-ated “action form,” which theycan print out and take to theirdoctors. The form outlineshealth “assets” and “needs.” As-sets might include not smokingor getting screening tests, whileneeds might pinpoint family his-tory or unhealthy habits.

Patients are also directed toWeb sites where they can learnmore about such issues as exer-cise, eating well, or makinghealth decisions. With this in-formation in hand, Wasson says,patients are equipped to takemore responsibility for their owncare, with regard to both pre-vention and treatment.

Complaint: In response to thecommon complaint that doctorshave too little time to get toknow their patients, Wasson’sprogram helps participating clin-ics make the best use of staff. Forexample, a nurse’s assistant cangather information about a pa-tient’s overall well-being andpass it along to the nurse or doc-tor who will see the patient at anoffice visit. In some cases—for apatient managing chronic pain,


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Tonsorial revelry on the Hanover Plain

G etting your head shaved is often a sign of rebellion, andsometimes even an indication of downright antisocial ten-

dencies. A head-shaving that took place at DMS in May, how-ever, was a selfless, community-minded act.

A satellite of the Upper Valley’s free clinic, the Good Neigh-bor Health Clinic, was due to open soon in the underservedMascoma region. Under the auspices of a Schweitzer Fellow-ship, second-year medical student Amy Noack had located asite for the new clinic, scrounged up equipment, and talked doc-tors into volunteering their time. What she hadn’t been able towangle was a source of funding for medications and other dis-posable supplies.

Enter Theodore Yuo, a first-year student. He and some ofhis classmates were brainstorming ways to raise the neededmoney, and the idea of a raffle came up. But what to raffle?Someone proposed chances on a head-shaving and, “as I havea reputation among the class for being the most ‘buttoned-down,’” says Yuo, “we thought it would be a hoot to see me abit outside my comfort zone.

“We were pleasantly surprised by the results,” he adds. Thegroup raised almost $300 by selling $2 chances to shave Yuo’shead “any way you want,” according to an e-mail promotingthe raffle. “Mullets, mohawks, Friar Tuck style . . . the possibil-ities are endless,” said the appeal. Yuo promised to wear what-ever outrageous “do” he ended up with for at least 24 hours.

His classmate Roy Wade (who, “ironically, encouraged meto try this out,” says Yuo) got to wield the shears. A crowd ofabout 40 people gathered to watch the fun, as Wade left hisclassmate semi-shorn. A day later, Yuo got rid of the locks thatremained and reported that he was “discovering the joys of eas-ier hair care, now that I’ve shaved it all off. We still need toraise more funds to make sure this project will continue,” headded, “but we consider this to be a very strong start.” A.S.

Ted Yuo, left, “bares” up after getting shorn by Roy Wade, right.

How well do doctors know theirpatients? Not well enough, saysJohn Wasson, M.D., DMS’s Her-man O. West Professor of Geri-atrics. A typical office visit maylast 10 minutes, but Wasson ob-serves that within “about 30 sec-onds” the physician will proba-bly interrupt the patient.

An elderly man coming inwith a complaint of joint pain,for instance, might have a hostof other problems affecting hishealth, such as emotional stressor limited social support, thatthe doctor will never hear about.Wasson believes it is essential fordoctors and patients “to get onthe same page” in order to im-prove health care.

Online: Based on 20 years of re-search, Wasson has developed aninexpensive, effective means ofpromoting communication be-tween patients and health-careproviders. It’s been used aroundthe country, including Mobile,Ala.; Long Beach, Calif.; and,most recently, Chicago. CalledHow’s Your Health (HYH),Wasson’s project is aimed at pri-mary-care practices and their pa-tients. Its key component is anonline questionnaire, tailored toage and gender, that helps pa-tients identify their individualhealth concerns, risk factors, andquality-of-life issues.

Topics range from symptomsto family history, from healthhabits to use of prescription med-ications. The survey also askssuch questions as “Do you have

Helping doctorsask their patients“How’s your health?”


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F or well over a century, DMS students have enjoyed swinging abat and chasing line drives. The photo on the left is of an 1887

DMS baseball team known as the Medics, and the images on theright depict the DMS Scrubs in action this spring.

Second-year student Ben Mailloux is captain and pitcher of theScrubs, the Class of 2005’s intramural softball team. The Scrubswon the Dartmouth-wide intramural championship last year andthis year made it to the semifinals but lost by three runs. Maillouxsays that 23 of his classmates are on the squad—about a third of theclass—and that leading the team has been a lot of fun.

While the Scrubs play all their games in Hanover, back in the

1880s and 1890s, the Medics played at other schools, traveling bytrain to Laconia, N.H.; Barre, Vt.; and Marlboro, Mass. They haduniforms emblazoned with red crosses and the letter “D.” Playerswere chosen by competition, and practices were held daily.

Many players, like those pictured in practice regalia in the pho-to above, went on to notable careers. Julius Haynes, Class of 1888(front, far left), was a surgeon in Toledo, Ohio, from 1890 to 1941.Edward Hallett, Class of 1887 (back, third from the right), was theoldest practicing physician in Gloucester, Mass., at the time of hisdeath in 1939 at age 75. And from their jaunty poses, it looks as ifthe Medics, like the Scrubs, enjoyed playing ball. M.C.W.

Baseball was as popular 116 years ago (above) as it is today (right).

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From the 1887 “Medics” to the 2003 “Scrubs,” baseball lives on at DMS

say—periodic phone calls fromthe nurse can keep the patienton track and cut down on thenumber of office visits.

For the cities taking part inHYH, the composite results ofthe patient surveys contribute toa big picture that would be hardto get otherwise. In Chicago—where a six-week initiative to getpatients to participate was spon-sored by the Chicago MedicalSociety, the Department of Pub-lic Health, and the Chamber ofCommerce—it was expected

that more than 10,000 peoplewould fill out the survey.

In a preliminary assessment of4,600 Chicago respondents,Wasson found that among pa-tients whose daily activities arelimited by pain, only 49% say aclinician is aware of the problem.Wasson says the three most fre-quently mentioned concerns, inChicago and elsewhere, are ex-ercise and nutrition, cancer andheart disease, and making thehealth-care system work better.

The success of the program—

with practices reporting patientsatisfaction rates as high as 90%,up from lows of 30%—has evencaught the attention of the U.S.military. HYH is now being usedby the Army, Navy, and AirForce. The State of New Jerseyis one of the newest locales tosign up. The CommonwealthFund “is offering small matchingfunds to interested communi-ties,” says Wasson.

To take the survey, visitwww.howsyourhealth.org.

Catherine Tudish

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The “How’s Your Health” Web siteincludes a health-issues survey, feed-back patients can share with their doc-tors, and links to health information.

Rebekah Kim ’05 Tom Kesman ’05


The subjects were dividedequally by gender and were allright-handed (the effects of gen-der and handedness will be stud-ied later). One group of subjectspeered at a dot, centrally locatedon a computer screen, whilehooked up to an EEG machine.Two objects would appear on ei-ther side of the dot—one grab-bable, one not. After about a sec-ond, horizontal bars would flash

over one of the objects. Bymeasuring the electrical

activity in the brain,the researchers

could de-terminewhere the sub-ject’s attention was fo-cused. The data indicatedthat subjects’ attentionwas drawn to the grab-bable objects, saysHandy, especial-ly when thoseobjects were onthe subject’s right.

Spatial: Then ScottGrafton, M.D., director of theDartmouth Brain Imaging Cen-ter, and Neha Shroff, a2002 Dartmouth Col-lege graduate who isnow a medical student at Van-derbilt, performed fMRI on an-other group of subjects. These re-sults confirmed that when a sub-ject’s spatial attention is drawnto a grabbable object, areas of thebrain associated with visuallyguided actions are activated.

So the investigators conclud-ed that the brain not only recog-nizes a pencil, a cup, or a screw-driver, but that our attention isdrawn to the item and our brainplans how to pick it up. “One of

the reasons why we might seegrabbable objects drawing our at-tention to their locations is thatto grab things is very complicat-ed,” Handy explains. “There’s aseries of computations the brainhas to make. When you look atsomething, you have to identifywhere it is, how big it is, and youhave to take that visual informa-tion and transform it into the ap-propriate motor commands toactually reach out and grab it.”The team’s results were pub-lished in the April 2003 issue ofNature Neuroscience.

What’s remarkable, Handyadds, is that the brain performsthese complex acts with hardlyany conscious thought. “Spatial

attention doesn’t justhelp us identi fy

what somethingis, like ‘I’m look-

ing at a pen,’”he explains. “It

actual-ly helps the motor

systems compute the programsnecessary for grabbing that ob-ject . . . attention not just for per-ception, but attention for ac-tion.” This understanding is onemore step toward figuring outjust how the brain works.

Attention: Further research mayhelp to address attention andobsessive-compulsive disorders.And, of course, advertising exec-utives can be counted on to usethis new knowledge about grab-bing attention to . . . well, grabour attention.

Joyce Wagner

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How often do we pick up a pen-cil, a coffee cup, or a screwdriverwithout consciously thinkingabout it—hardly even looking atthe item? Ever wonder howthat’s possible?

Scientists have long suspect-ed that when a tool or some oth-er grabbable object enters our pe-ripheral vision, the brain notonly turns its attention to theobject but also begins the com-putations necessary to pick it up.Neuroscientist Todd Handy,Ph.D., together with several oth-er Dartmouth researchers, set outto prove that. What he discov-ered is that grabbable items canaffect visual attention, but thatit matters where in the line of vi-sion the item is located.

“There’s a fundamental dis-tinction between vision for per-ception and vision for action,”explains Handy, a research assis-tant professor of physiology andbrain science. “What we demon-strated is that things that we cangrab—such as tools, cups, thingsthat accord some kind of motoraction—are capable of grabbingour attention automatically.”

Auspices: Under the auspices ofMichael Gazzaniga, Ph.D., di-rector of the Center for Cogni-tive Neuroscience, Handy’s teamset up a two-part experiment.Using electroencephalography(EEG) and functional magneticresonance imaging (fMRI), theteam recorded the brain respons-es of subjects viewing grabbableas well as non-grabbable objects.

Visual attentionmay involve morethan perception

To what extent does medicalpractice reflect scientific evi-dence? Far from perfectly, ac-cording to a recent study by theOutcomes Group at the VAMedical Center in White RiverJunction, Vt.

“We are interested in study-ing how rational medical prac-tice is,” explains Brenda Siro-vich, M.D., an assistant profes-sor of medicine at DMS and thelead author of the study. Recent-ly, she and colleagues comparedthe screening rates for prostatecancer and colorectal canceramong men in the U.S. in astudy published in the March 19issue of the Journal of the Ameri-can Medical Association.

There is no current evidencethat screening for prostate can-cer by means of a blood test forprostate specific antigen (PSA)is effective in reducing mortality.But numerous randomized, con-trolled trials have shown thatscreening for colorectal cancerleads to substantial reductions inmortality. Although prostatecancer claims more lives, co-lorectal cancer accounts formore premature deaths. So ifpractice patterns were based onscientific evidence, then screen-ing rates for colorectal cancershould be higher than those forprostate cancer.

Yet using data from a federalsurvey called the Behavior RiskFactor Surveillance System, theDMS researchers found that75% of men over age 50 report-

Screening ratesdon’t match upwith the evidence


ed having had a PSA test, butonly 63% had been screened forcolorectal cancer. “There is evi-dence linking colorectal cancerscreening with reduced mortali-ty from colorectal cancer,” saysSirovich. “Yet more men are get-ting the other screening test,which is perplexing.”

Perplexing: Equally perplexingwas the discovery that the agegroup with the highest rate of re-cent prostate-cancer screening(that is, within the last year) was70- to 79-year-olds. “Most peo-ple who look at the benefit ofprostate-cancer screening agreethat the least likely age group tobenefit . . . are older men,” ex-plains Sirovich. That’s becausealthough the risk of havingprostate cancer increases withage, the chance that it will be aslow-growing form of the diseaseincreases even more.

And with any screening test,the benefits tend to wane withage because the population hasan increasing burden of otherdiseases, so the likelihood thatthe screening will prolong theperson’s life expectancy falls.

Sirovich also notes that oldermen “are, in fact, the most like-ly to be harmed by screening.”That’s because any screeningtakes a population of individualswho have no signs or symptomsof disease and subjects some ofthem to interventions theywould not otherwise have re-ceived. When you sign up for ascreening test, says Sirovich, yousign up for a potential cascade ofevents—perhaps a biopsy; per-haps prostate surgery, which canresult in impotence, inconti-nence, or prolonged hospitaliza-

tion; perhaps radiation therapy,which, especially in older pa-tients, can have long-term con-sequences.

Not only does the evidenceindicate a greater benefit fromcolorectal screening, but so doconsensus guidelines by experts.Those for prostate cancer in-clude both pros and cons of PSAtests. But colorectal guidelinesstrongly recommend screeningstarting at age 50 for both menand women. Sirovichnotes, however,that the re-searchers“were notinterestedi n p r o -m o t i n gone [ test ]and pickingon the other,but in pointing outthe mismatch.”

What could ac-count for the mis-match? One hypothe-sis is that men are morelikely to know other menwith prostate cancer, so the testfor that disease may seem moresalient. The number of peopleliving with prostate cancer is atleast three times that of peoplewith colorectal cancer, saysSirovich, in part because the rateof screening for prostate canceris so high.

Phenomenon: Sirovich explainsa known phenomenon of screen-ing: The more you screen, themore symptomless, mild cases ofthe disease you find. Survivalrates go up because you’re find-ing more treatable forms of thedisease. It’s assumed that the

screening is responsible for theimprovement in survival. Thatleads to an even greater empha-sis on screening and the identifi-cation of still more very mild cas-es. Hence it’s more likely a givenperson will know someone who’sbeen diagnosed with the disease.

Publicity: Another theory isthat publicity—often in the formof celebrities with the disease—results in higher rates of prostate-cancer screening.

“If the [proven benefits fromthe] tests were equal . . . and

both cancers had as big animpact on society in[terms of] years of lifelost to cancer, then youw o u l d e x p e c t t h e

screening rates to beequal,” explains

Sirovich. Yetnot only areall the bene-fits lower forprostate can-

cer, but the rateof screening for it

is higher.Sirovich emphasizes

again that she is not taking a po-sition on screening but merelymaking an observation. “Isn’tthis interesting,” she says. “Thisis how we’re practicing medi-cine, and this is what the evi-dence shows.

“We need to look more close-ly at where that mismatch is. Ifit’s that people don’t know, thenwe want to make sure that peo-ple know. If it’s that they knowand are making decisions basedon what they know, we’d be in-terested to hear why they’remaking those decisions.”

Katharine Fisher Britton

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A trio of Dartmouth researchers—from two different DMS de-partments and from the College’sbiology department—have beenworking for years to unlock thesecrets of biological clocks. At-tacking the issue on severalfronts are Jay Dunlap, Ph.D., aprofessor and chair of genetics;Jennifer Loros, Ph.D., a professorof biochemistry; and C. Robert-son McClung, Ph.D., a memberof Dartmouth College’s biologydepartment.

Genes: Dunlap and Loros (whoare married to each other)—with a pair of British colleagues,including former DMS postdoc-toral fellow Susan Crosthwaite,Ph.D.—recently discovered thatan unusual form of RNA knownas antisense appears to regulatecore timing genes in the breadmold Neurospora’s biologicalclock. And McClung, who was apostdoctoral associate in Dun-lap’s lab before establishing hisown lab more than 15 years ago,has uncovered evidence of twocircadian clocks working withinthe same tissue of the floweringplant Arabidopsis thaliana.

The DMS results, publishedin Nature, are important becausethey reveal how antisense RNAsmight affect a wide variety ofprocesses. The findings, write theauthors, “provide an unexpectedlink between antisense RNAand circadian timing.”

Usually, messenger RNA(mRNA) transcribes the geneticinstructions contained in DNA,

Antisense DNAhelps make senseof clock secrets


then translates the informationto form a protein molecule.

But when a strand of mRNAforms a duplex with a secondstrand of RNA, the translationprocess is turned off. The firststrand is called “sense” RNA, be-cause it can normally be decod-ed to form a protein; the secondstrand is called “antisense,” be-cause its nucleotide sequence isthe complement of the “sense”message. And this sense-anti-sense combination renders thesense strand incapable of decod-ing the DNA recipe to yield aprotein product.

In normal bread mold strains,light triggers the cycles of anti-sense and sense RNA transcriptsrelated to the frequency gene.But in mutant bread mold strains—ones that have been geneti-cally altered to abolish light’sability to induce the antisenseRNA—the internal clock timeis delayed and the resetting ofthe clock by light is altered.

Stability: If similar environ-mental factors regulate bothsense and antisense transcripts,the authors suggest, a role for an-tisense frequency RNA might beto confer the ability to keep ac-curate time by limiting the clockresponse to extremes in the en-vironment. And other antisenseRNAs might be involved inmaintaining internal stability inother organisms.

“Antisense RNA may play arole in regulation of clock genesin people,” says Dunlap. “Mis-regulation of circadian clocksand their responses to light hasbeen implicated in several kindsof mental illness or affective dis-orders. And misregulation of

clock genes has been suggestedas an origin of some cancers.”

McClung, whose early workwith Dunlap focused on Neu-rospora, is still looking at biolog-ical clocks but in different or-ganisms now. His recent findings,published in the online editionof the Proceedings of the NationalAcademy of Sciences, suggest thatplants may respond to seasonalchanges by integrating informa-tion from at least two environ-mental signals—light and tem-perature.

“This is exciting, because thisis the first good example of twoclocks operating within a singletissue in any multicellular organ-ism,” McClung says. “We’re notquite at the point where we canfind out if there are two clocks

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Nurturing better listening, more caring

I t’s really awesome to listen to people tell their own storiesand have the rest of the people in the group be moved by

them,” says Joseph O’Donnell, M.D., a professor of medicineand DMS’s senior advising dean.

O’Donnell and Kathryn Kirkland, M.D., an assistant pro-fessor of medicine, are leading a new community discussiongroup called Communities of Care. The program is funded bythe New Hampshire Humanities Council.

The group meets once a month to discuss short stories andpoems and watch portions of films, all dealing with a specificmedical theme—such as the patient’s perspective, the doctor’sperspective, or dying and illness. Participants include variouscommunity members: retirees, hospital administrators, nurses,social workers, yoga teachers, and a filmmaker.

Following a meal, the group sits in a large circle as O’Don-nell and Kirkland lead discussions of the week’s assigned read-ings—such as stories from Jerome Groopman’s Measure of OurDays and essays on altruism from A Life in Medicine, whichO’Donnell coedited. Another week, the group watches part ofthe film The Doctor, in which William Hurt plays a surgeon whotreats his patients with sarcasm and disrespect, until he himselfis diagnosed with throat cancer and discovers what it is like tobe a patient. The surgeon’s motto in the film—“Get in, fix it,get out”—triggered a lively discussion. “We talked about fixingversus healing, versus serving, versus helping. You fix somethingbecause it’s broken. You serve somebody as an equal,” explainsO’Donnell.

His philosophy is that as health-care professionals and pa-tients read and discuss literature together, and share their per-sonal stories, they become better listeners. “We’re trying to pro-duce communities of care,” he says. “How do we establish com-munity? How can this literature group be a community? Howcan we live in community?” M.C.W.

Joe O’Donnell, at left, leads a recent Communities of Care discussion.

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Dartmouth Medical School researchersJennifer Loros and Jay Dunlap, picturedbelow, have spent many years teasingout the mechanisms of biological clocks.

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operating in a single cell, butthat’s our goal.”

Much has been discoveredabout biological clocks over thepast 30 years, since Dunlapgained recognition for identify-ing what he calls the clock’s“cogs and gears.”

Findings: Last year, Dunlap’s labrevealed that a single proteincalled White Collar-1 does dou-ble duty: it perceives light and italso turns on the central compo-nent of the clock, the frequencygene. Other findings made atDMS include the discovery thattemperature may be more influ-ential than light in setting cells’biological clocks and that signalstell bread mold when to send outspores, delineating how theclock is assembled and how lightresets the biological clock.

How much else is there todiscover about circadian clocks?

“Who knows,” says Dunlap. Laura Stephenson Carter

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What’s in a (school’s) name?

T here’s something to be said for referring to Dartmouth Med-ical School simply by its initials: DMS is short and easy to

remember. But that simplicity masks a history of long and con-fusing names for the institution. An 1824 announcement inthe Boston Telegraph used “N. Hampshire Medical Institution,”“The Medical College,” and “The Medical Institution of theState of New Hampshire,” all in the same item.

That last name probably wins the prize for length, though“Medical Institution at Dartmouth University” gives it a runfor the money. But despite their wordiness, these names mayhave raised more questions than they answered. “The MedicalCollege” as often as not referred to the building rather than theinstitution. Names with “university” in them were anathema ina day when many loyalists did not want Dartmouth Collegeconfused with anything of the sort. And any name with “NewHampshire” in it made DMS sound like a state school. But theindiscriminate way different names got used (sometimes in thesame breath) makes it clear that no one in the 19th centurywas much worried about what the place was called.

Other names used back then include “Dartmouth MedicalInstitution” and “New Hampshire Medical Institution.” Pithyand actually pretty accurate for the first century of DMS’s exis-tence was the name perhaps used most frequently: “Medical De-partment.” But somehow that didn’t have the right gravitas asthe School came of age.

When Professor of Surgery Phineas Sanborn Conner said inthe late 1800s that the official name had “always” been “Med-ical Department of Dartmouth College,” he was mistaken. Dur-ing that very period, Dean William Thayer Smith had “Dart-mouth Medical School” (at last!) emblazoned on his stationery.

Perhaps the most grandiloquent but least-used name seemsto have fallen into the dustbin of history: “Dartmouth MedicalTheatre.” Now there’s a stage to play on! C.E.P.

An 1899 graduation program bears one of DMS’s tamer past names.

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When a close childhood friendfollowed her to college at MIT,Urvi Pajvani, now a second-yearstudent at DMS, was delighted.She was equally devastated whenher friend committed suicide bysetting her dorm room on fire.

That experience, plus Paj-vani’s interest in mental health,led her to construct a project onteen depression and suicide pre-vention in the Upper Valley. “Ireally wanted to do something inmemory of my friend,” Pajvaniexplains. “It was horrendous andsomething that shouldn’t hap-pen to someone her age. Like somuch of medicine, depressionand suicide are completely pre-ventable, but people just don’tfocus on the prevention.”

Signs: Pajvani was originallyinterested in talking to teensabout warning signs for suicideand places they could find help.But her project—which wasfunded by the Schweitzer Fel-lowship Program—changed aftershe did some research.

She discovered that the sur-geon general had issued a state-ment concluding that interven-tional programs were ineffectiveat preventing adolescent andteen suicide. In fact, the state-ment argued that educationalprograms could be detrimentalby causing otherwise healthyteens to consider suicide.

In light of this information,Pajvani realized she could havemore impact by educating physi-cians and other health-care

Student triesto turn the tide of teen suicide


providers in the region. Shecompiled statistics on how manyadolescents attempt or commitsuicide in the Upper Valley andcompared them to national data.In searching for patterns, she dis-covered that of teens who com-mit suicide, 80% of boys also usealcohol and smoke tobacco and60% of girls also have body-im-age concerns. She believes it isimportant for physicians to bealert for these connections intheir patients.

Packet: Pajvani developed aninformation packet that de-scribes screening techniques andconditions associated with sui-cide, such as a family history ofmental health problems or theuse of phrases such as “No onewould miss me.” She especiallytargeted pediatricians, hoping tostrengthen their ability to recog-nize teen depression.

“I just want to remind health-care providers that this is a prob-lem. I at least want to make itfresh in their minds,” Pajvani

says. “I think thatdoctors know riskfactors for suicidebut don’t thinkabout them on adaily basis.”

Having animpact on a com-plex problem liketeen suicide isdifficult, Pajvanicame to realize.“I guess I won’tever see tangibleresults from myproject,” she says.“I won’t ever seewho I am helpingdown the road.

But maybe my words will helpone person who i s helpinganother person.”

That indirect effect can bepowerful, says her mentor for theproject, psychologist PhilipWyzik of West Central Behav-ioral Health, a member of theDartmouth-Hitchcock Alliance.“The issue of suicide is a signifi-cant health-care problem in oursociety,” Wyzik explains, but “isoften overlooked. . . . However,suicide is preventable if peopleseek help and if others reach out.Urvi’s work will contribute to in-creasing awareness.”

Pajvani hopes to help at-riskteens more directly when she be-comes a physician. She has con-sidered entering either pediatricsor psychiatry, but she knowswhat she’s learned will help herin any specialty. “If you’re goingto be a doctor,” she says, “youshould be in tune with people’smental health as much as . . .with their physical health.”

Katrina Mitchell

soliciting submissions for the in-augural issue, which they plan topublish in an online edition thisfall. They are looking for origi-nal, unpublished short stories,works of literary nonfiction, po-ems, artwork, or photographs.Their hope is to eventually pro-duce a print version of Lifelinesas well.

Li’s vision is that the projectwill serve as “a thread that windsamongst all those who have beentouched by the medical experi-ence . . . a literary collage thatoffers a much-needed creativeoutlet for doctors and patientsalike.

“It is our hope,” he says, “thatthis journal will enhance the at-mosphere of the health-carecommunity by instilling in itsreaders a respect for the endur-ing human spirit and a profoundhope for better understandingand dialogue between doctorsand patients.”

Guidelines: Submission guide-lines are available at the URL inthe caption below, or by writingto [email protected] orto Lifelines, DMS, Hanover, NH03755-3833.

Alan Smithee

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The word “lifeline” acquired anew meaning a few years ago,thanks to the TV game showWho Wants to Be a Millionaire.Suddenly, the word implied notjust literal survival for roped-together mountaineers, but achance for quiz contestants tosurvive another round of play.

Meaning: Now, a group of Dart-mouth medical students is tryingto give the word yet anothermeaning—one having to dowith survival of the soul.

Lifelines is the name of anascent project to publish “aDartmouth Medical School lit-erary journal.” The mission ofthe journal, says its founder andeditor-in-chief, first-year studentSai Li, “is reflected in its name—to connect the experiences andperspectives of all participants inthe medical community, in orderto facilitate better communica-tion and understanding.”

The editors plan to publish,according to the project’s Website, “works of art and word that,through their poignant accountsof everyday lives, as [the famousdoctor-poet William Carlos]Williams wrote, offer us that‘glimpse of something, from timeto time, which shows us that apresence has just brushed pastus.’ ” Lifelines will feature thework of DMS students and alum-ni, of DMS and DHMC health-care professionals, of patients atDHMC-affiliated hospitals, andof prominent writers.

Li and his colleagues are now

Medical studentsplan to publish“a literary collage”

Urvi Pajvani has spent a good bit of time during the lastyear—when she wasn’t immersed in her medical stud-ies—working to combat teen suicide in the region.

This is the home page of the new DMSliterary journal’s Web site. Its URL iswww.dartmouth.edu/dms/lifelines/.

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When Mark McGovern, Ph.D.,left his Chicago psychology prac-tice in July 2001 to join theDMS faculty, he was expectingto work with Robert Drake,M.D., Ph.D., director of the NewHampshire-Dartmouth Psychi-atric Research Center (see thisissue’s “Faculty Focus” profile onpage 66). McGovern’s expertiseis in treating patients dually di-agnosed with mental illness andsubstance abuse problems.

But then the chair of psychi-atry, Peter Silberfarb, M.D.,asked McGovern to attend somemeetings at Dartmouth aboutsubstance abuse. McGovern, anassociate professor of psychiatry,was surprised to find an “incred-ibly diverse” group of people in-volved—former U.S. SurgeonGeneral C. Everett Koop, M.D.;Joseph O’Donnell, M.D., senioradvising dean at DMS; Jack Tur-co, M.D., director of the Dart-mouth Health Services; otherclinicians and researchers; facul-ty from Native American Stud-ies and the Departments of Eng-lish and Russian; staff from thelibrary and the chaplaincy; andeven some alumni.

Desire: “They were talkingabout a desire to do somethingabout substance use at Dart-mouth. . . . They were talkingabout drunks that were showingup at the emergency room andbeing sent away. They were talk-ing about everything,” McGov-ern recalls. “It was really pas-sionate—but incredibly vague.”

Many of the attendees hadparticipated in an interdisciplin-ary Dartmouth course called“Alcohol, Addiction, andHealth,” taught by Gail Nelson,Ph.D., a research associate inpsychiatry. “Gail in a very cre-ative way brought in multidisci-plinary faculty and alums andstudents who were in recovery totalk about addiction and situatedit in the context of literature andculture and art, from film topainting,” says McGovern. (Seethe Summer 2001 issue for moreabout this course.)

Within months of McGov-ern’s arrival, the group con-vinced Dartmouth Provost BarryScherr to fund a DartmouthCenter on Addiction, Recovery,and Education (DCARE) fortwo years. McGovern was askedto be its executive director andNelson the associate director.

It quickly became apparentthat DCARE’s most importantrole would be as a coordinator.Many people at Dartmouth andin the community were alreadyinvolved in substance abuse ini-tiatives, but McGovern was sur-prised that “a lot of them didn’tknow about one another.” Com-ing from an urban area, he as-sumed that “in a place like this,everybody knew . . . what every-body else was doing.”

DCARE decided to createseveral task forces to keep itswork focused. “Our job at thecore would be to keep the ballmoving on these task forces,”says McGovern. “The task forcesturned out to be the heart andsoul of the whole thing.”

The physician training taskforce, for instance, determined

that DMS “wasnot doing a badjob” incorporat-ing substanceabuse issues intothe curriculum,explains DonaldWest, M.D., thec h a i r o f t h a tgroup. “But therewas nowhere torefer patients fortreatment.”

Talk: “We weretalking the talk,but not walkingthe walk,” saysO’Donnell, whois cochair of theDCARE planning council withKoop. “If we weren’t dealingwith the treatment, it would un-dermine what was being taughtin the classroom.” McGovernagrees, saying that medical stu-dents “had this great coursework,” but later, during theirclinical rotations, “were seeingrole models . . . talking about‘Those hopeless people’ and ‘Wedon’t treat them here.’ . . . Notthe best role models.”

A subcommittee of that taskforce developed a proposal for anintensive outpatient treatmentprogram at DHMC. The propos-al is under review by the admin-istration.

The community task force,cochaired by O’Donnell, is push-ing for a residential treatmentcenter for adolescents in the Up-per Valley. Now adolescents whoneed residential treatment haveto go as far away as New York oreven Arizona. “The further awaytreatment takes place,” McGov-ern explains, “the more difficult

the reentry is and the more like-ly relapse will take place.”

The community task forcealso facilitates DMS student in-volvement with abuse issuesthrough smoking cessation clin-ics, court diversion programs,and the College’s fraternities andsororities.

Another task force is con-ducting an ethnographic study ofsubstance use at Dartmouth, todetermine how alcohol anddrugs are woven into the fabricof the College’s culture.

Forums: DCARE’s other activ-ities include coordinating publicforums to build awareness aboutsubstance abuse issues and meet-ing with government leaders.The organization has become “aplatform to facilitate, to inspire,to encourage all these kinds ofactivities in all these differentfronts,” explains McGovern.

Thanks to DCARE, “there’sa lot of momentum,” concludesO’Donnell.


Substance abuse:Molding passioninto momentum

Mark McGovern arrived at Dartmouth two years ago andshortly found himself heading up a substance-abuse proj-ect that is bringing diverse constituencies together.

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All of us have considered atsome time or another countingexceedingly large numbers—thestars in the sky, the grains of sandon a beach. But for Dartmouthcomputer scientist Bruce Don-ald, such a task is not a passingfancy but his life’s work.

Goal: The ambitious goal of hiscurrent project is to work out thestructures of all the proteins innature—both plant and ani-mal—under the auspices of afive-year, $1.2-million grantfrom the Institute of GeneralMedical Science.

It’s rare for a computer scien-tist to be the principal investiga-tor on a grant from the NationalInstitutes of Health, says Donald,but he feels up to the challenge.When asked how many proteinsmight be involved, he replies,“Let’s start with a human. Thenumber of proteins is a functionof the number of genes. Thatnumber keeps changing, but cur-rently it’s around 22,000.

“I’d be very surprised if the to-tal [number of proteins for allspecies] is less than 100,000,”Donald continues. “I would notbe surprised if it was a million.But I would be surprised if it weremore than two million.”

How does one go about sucha task? A good interdisciplinaryteam is the key. First, bio-chemists clone a gene, coax it toexpress a protein, and then puri-fy the protein to the nth degree.The protein not only has to bepure, but each molecule has to

Probing structure of every proteinis a massive job

Redundancy is often a goodthing—in plane engines, com-puter backups, or emergency ex-its. But biological redundancy—the existence of multiple bio-chemical pathways to one effect—is a problem when it comes totreating cancer or, for that mat-ter, any disease.

That’s because a drug or radi-ation may block one pathwaybut not the ultimate effect. Forthis reason, it has long been rec-ognized that combining two ormore drugs that have differentmechanisms may produce a bet-ter result—a phenomenon calledsynergy. Multidrug therapy withfour or more agents is now com-mon in cancer chemotherapyand AIDS therapies.

Twist: A new twist in combi-nation therapy was the subject ofa recent paper in Cancer Researchby a team of investigators atDartmouth Medical School andDartmouth’s Thayer School ofEngineering.

For the past decade, there’sbeen interest in combining pho-todynamic therapy (PDT) andradiation to treat some cancers.“But,” says Brian Pogue, an asso-ciate professor of engineering,“although additive effects wererecognized, until our study noone had been able to show a syn-ergistic effect between PDT andradiation. One reason is that pre-vious studies largely focused ontest systems in cell cultures, andwe now know that some types ofsynergism between PDT and ra-

Together is betterthan alone, findsDMS-Thayer team

fold in precisely the same way.The protein must then be dis-solved in water and subjected toso-called solution nuclear mag-netic resonance (NMR).

In this technique, the spec-trometer makes tens of thou-sands of measurements of bondangles and distances between hy-drogen nuclei. Just as numerousmeasurements by a surveyor gointo the creation of a topograph-ical map, the NMR data con-tains all the elements needed toprepare a three-dimensional mapof the protein. The problem ishow to extract them.

It is at this point that Don-ald’s group steps in. Their work isbased on an undergraduate hon-ors thesis by Alik Widge, a 1999Dartmouth College graduatewho is now an M.D.-Ph.D. stu-dent at Carnegie-Mellon. WithDonald’s help, he formulated acomputer algorithm for deter-mining protein structure fromthe NMR data; his thesis wonDartmouth’s Kemeny Comput-ing Prize. The original algorithmhas since been refined by Don-ald’s group, and related algo-

rithms have been developed.Now the group is testing themon NMR data collected from avariety of sources, at DMS andelsewhere.

Mass: The team is also prob-ing protein structure using tech-niques complementary to NMR,including x-ray crystallography,mass spectrometry, and compu-tational modeling.

The applications of the workare legion. For example, know-ing the structure of a receptorcould contribute to developingmore specific drugs, more potentdrugs, or drugs with fewer side ef-fects. Or knowing the structureof an enzyme could suggest waysof modifying it to produce moreefficient catalytic activity.

By looking at mass spectrom-etry data on serum from patientswith prostate cancer and fromnormal controls, Donald and acolleague were able to constructwhat’s called a “learning” algo-rithm that distinguishes with anaccuracy of better than 97% be-tween cancer patients andhealthy patients. The resultswith ovarian cancer were evenbetter—100% accuracy.

Size: Another possible appli-cation may be measuring serumproteins during chemotherapy toquickly assess treatment out-comes. Now, oncologists mustwait before they can evaluate atherapy’s effectiveness. Butchanges in serum proteins mayprove to be a more sensitive in-dicator of efficacy than, say, re-gression in tumor size.

To keep tabs on Donald’sprogress, check out this site—www.cs.Dartmouth.edu/~brd/.

Roger P. Smith, Ph.D.

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Focused radiationmeans less damage,more chance of cure

ture, impair blood flow, andblock oxygenation of the tu-mor—decreasing the effective-ness of the PDT.

If, instead, PDT is deliveredthree hours after VP, most of theVP has moved into the tumorcells and other tissues, optimiz-ing the effect of the PDT. More-over, singlet oxygen tends todamage mitochondria, the pow-er plants of cells, causing theoxygen content of the tumor torise above normal levels.

This leads to increased cell-killing when the tumor is sub-jected to radiation, which targetsDNA. On this schedule, the twotreatments together are clearlysuperior to the sum of both bythemselves.

The tumor model used in theDartmouth study was a mousesubcutaneous fibrosarcoma, sothat the laser could be appliedexternally. But what about deep-er tumors? Julia O’Hara, Ph.D., aresearch associate professor of ra-diology, explains that the PDTcan also “be delivered by fiberoptics, so the delivery system canbe threaded to internal tumors.”In the case of a bladder tumor,for example, the fiber opticscould be introduced through acatheter in the urethra. Even tu-mors in the abdominal cavityand parts of the chest cavitycould be accessed through smallincisions.

When asked what’s next forthe team, Pogue replies, “Stepone is the same as in all researchprojects—namely to get thegrant renewed. After that, weplan to try to target approachesto prostate cancer.”

Roger P. Smith, Ph.D.

ing critical time periods, there issome degree of selectivity of thetumor for the porphyrin.”

Then, says Swartz, a laser isprecisely focused on the tumor,further increasing the specificityof the treatment. This convertssome of the oxygen in the tumorto a highly toxic free-radicalform called singlet oxygen,which destroys tumor cells.

Timing: Timing is all-impor-tant, because PDT with VP canalter tumor oxygen tension in ei-ther direction, depending on theinterval between the processes.If phototherapy is delivered soonafter the VP, most of the VP willstill be in the blood and the tox-ic singlet oxygen will be pro-duced in the blood vessels. Thiseffect can damage the vascula-

diation may only be demonstrat-ed in whole animals.”

Harold Swartz, M.D., Ph.D.,a professor of radiology at DMSwho collaborated with Pogue onthe study, outlines a typical treat-ment: “One would begin by in-jecting a semi-synthetic por-phyrin, verteporfin [VP], intra-venously. The VP would distrib-ute throughout the body, al-though there seem to be some-what higher concentrations intumor tissue than in normal tis-sue. Perhaps this is because theblood vessels in tumor tissues areleakier than they are in normaltissue, and this allows more VPto leak into the tumor. More-over, VP seems to be clearedfrom normal tissue more rapidlythan from tumor tissue. So dur-

Brian Pogue, who’s on the faculty at Dartmouth’s Thayer School of Engineering, iscollaborating with colleagues at Dartmouth Medical School to find ways to boost theeffectiveness of cancer therapies by carefully timing their administration.

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N Since the first cancer patient wastreated with radiation therapy in1896 (the same year that the firstclinical x-ray in the nation wastaken at Dartmouth), techniquesfor killing tumors with focusedenergy have changed dramati-cally. Today, half of all cancer pa-tients receive radiation treat-ment to kill cancer cells andcontrol their spread.

Beams: The problem is thatconventional radiotherapy—inwhich a medical linear accelera-tor delivers large, uniform beamsof radiation to a tumor site—may not only kill cancer cells butalso damage healthy tissue sur-rounding the tumor.

But now, “recent advances incomputers and technology haveenabled us to increase and focus

Radiologist Eugen Hug adjusts DHMC’snew radiotherapy device for a patient.The massive instrument stands ninefeet tall and weighs almost 10 tons.

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F R O M O U R P A G E S

In this section, we highlight visual and textual tidbits frompast issues of the magazine. These messages from yesteryear re-

mind us about how fast some things in medicine (and in life)change, as well as about some timeless truths.

From the Spring 1978 issueAlmost exactly 25 years ago, DMS alumnus Irving Kramer ’33went “Out on a Limb”—in an article of that title—and madesome predictions about the future of medicine.

“Those of us who studied anatomy under Dr. Frederic Lord,”he wrote, “can imagine what our reactions would have been ifhe had predicted that one day a pump oxygenator would beconnected to the circulatory system, that a surgeon would thenincise the heart muscle, work on the valves, sew it up, and thenshock the heart to start it again—we would have consideredhim demented!

“The year 2000 is no longer a distant date of concern onlyto science fiction buffs,” went on Kramer, an internist. “Overhalf of the physicians in the United States today will still bepracticing in 2000. So it is none too soon to ask: ‘What will bethe state of the healing art at the turn of the century?’

“A breakthrough can be expected in the 1990s with the in-troduction of antiviral therapy for certain types of cancer,” hepredicted. “In the 1980s, besides a wide variety of more effec-tive vaccines, there will be a universal virus vaccine. . . . Arti-ficial hearts will largely have replaced human or animal trans-plants by the 1990s. . . . The widespread availability of video-phones, interactive television, and computer terminals withinhomes may allow patients to receive a large proportion of theirmedical care without having to travel to a hospital, clinic, or of-fice. . . . By 1990, the costs of comprehensive health care willbe covered by tax-supported national health insurance or oblig-atory health insurance.” Kramer, who died in 1993, was clear-ly prescient in some regards—and game in his willingness topeer into a brave new world he didn’t quite live to see.

Legions of DMS students learned anatomy from Professor Fred Lord.

Controversies & Conversations inCutaneous Laser Surgery. Editedby Kenneth Arndt, M.D., andJeffrey Dover, M.D., both ad-junct professors of medicine atDMS; American Medical Asso-ciation Press; 2002. This bookexamines new laser techniques

and providesguidance onusing lasers ina variety ofclinical situa-t ions . I t in -cludes detailsabout laser re-

surfacing; photorejuvenation;treatment of vascular anomalies,leg veins, psoriasis, and scars;skin cooling; and novel ap-proaches to skin rejuvenation.

Manual of Dermatologic Thera-peutics. By Kenneth Arndt,M.D., an adjunct professor ofmedicine at DMS; and KathrynBowers , M.D. ; L ippincottWilliams & Wilkins; 2002. The

revised editionof this manualprovides infor-mation on thepathophysiolo-gy, diagnosis,and therapy ofa va r i e ty o f

common skin disorders. It in-cludes definitions and descrip-tions of each condition and dis-cusses symptoms, clinical find-ings, assessments, and potentialtherapeutic interventions, in-cluding medications.

New on the bookshelf:Recent releases byDMS faculty authors

radiation where we need it—with less radiation to surround-ing tissues,” says Eugen Hug,M.D., chief of the Section of Ra-diation Oncology and associatedirector of DHMC’s Norris Cot-ton Cancer Center. “Today wecan deliver a higher dose, de-crease side effects, and increasethe chance of cure. We were notable to do this for many patients10 years ago.”

Precise: In May, DHMC doc-tors began treating patients withIntensity Modulated RadiationTherapy (IMRT), which usescomputer-generated images toplan and deliver a radiation doseprecisely the shape and depth ofthe tumor.

A computer-controlled de-vice called a “multi-leaf collima-tor” uses up to 120 tungsten fin-gers, or leaves, to sculpt the radi-ation beam to conform to the tu-mor. The linear accelerator canalso be moved to target all di-mensions of the tumor.

Tissues: “Splitting the tumorinto different segments improvesdose delivery and increases thechance of completely eliminat-ing the tumor,” Hug explains.“IMRT can be custom-tailoredto the requirements of the tumorand the critical normal tissuesaround it.”

Studies have indicated thatIMRT is especially effective intreating tumors of the brain,head, neck, prostate, and lung.With conventional radiotherapydevices, it’s difficult to deliver ra-diation to tumors located atthose sites in doses that are highenough or that don’t result in se-vere side effects.

Mary Hawkins

William Wickner, M.D., the JamesChilcott Professor of Biochem-istry, was recently elected a fel-low of the American Academyof Arts and Sciences. Among the

other new fel-lows and for-eign honorarymembers thisyear were KofiAnnan, secre-tary-general oft h e U n i t e d

Nations; journalist WalterCronkite; and Nobel Prize-win-ning physicist Donald Glasner.Wickner was recognized for hisstudies on cell membranes andprotein movement.

John Wennberg, M.D., the PeggyThomson Professor of the Evalu-ative Clinical Sciences and di-rector of DMS’s Center for theEvaluative Clinical Sciences, re-ceived the 2003 Health Quality

Award fromthe NationalCommittee forQuality Assur-ance; it recog-nizes contribu-tions made to-ward improv-

ing the quality of health carethrough research, public policy,or public education.

Thomas Oxman, M.D., a professorof psychiatry and of communityand family medicine, was electedto the board of directors of theAmerican Association of Geri-atric Psychiatry.

Frances Friedman, M.D., an assis-


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Worthy of note: Honors, awards, appointments, etc.

tant professor of medicine emeri-ta, was one of 40 physicians na-tionwide to receive a LaureateAward from the American Col-lege of Physicians, for her workfor the ACP.

Robert Racusin, M.D., an associ-ate professor of psychiatry and of

pediatrics, wasthe recipient ofthe 2003 Psy-chiatrist of theYear Award forNew Hamp-shire. It is pre-sented by the

state’s chapter of the NationalAlliance for the Mentally Ill.

William Boyle, M.D., a professorof pediatrics, was recently select-

ed as the re-cipient of theGranite State’s2003 Pediatri-c i a n o f t h eYear Award.The award ispresented an-

nually by the New HampshirePediatric Society.

Catherine Pipas, M.D., an associ-ate professor of community and

family medi-cine, was elect-ed cochair ofthe NationalSteering Com-mittee for theS o c i e t y o fTeache r s o f

Family Medicine’s PredoctoralEducation Committee.

Robert Harbaugh, M.D., a profes-sor of surgery and of radiology,was selected by the AmericanStroke Association, a division ofthe American Heart Associa-tion, to serve as a member-at-

large of the Stroke LeadershipCommittee.

Six faculty members werehonored as the inaugural recipi-ents of Dean’s Faculty Awards—a new DMS award recognizingexcellence in four different areas.The Senior Faculty Award waspresented to Donald St. Germain, M.D.

(pictured atleft), a profes-sor of medicineand of physiol-ogy as well asacting chair ofthe Depart -ment of Medi-

cine. Honored for basic sciencewas George O’Toole, Ph.D., an assis-tant professor of microbiologyand immunology; for clinical in-vestigation, Lisa Schwartz, M.D., andSteven Woloshin, M.D., both associ-ate professors of medicine and ofcommunity and family medicine;for teaching and clinical care,Joshua Lee, M.D., an assistant pro-fessor of medicine; and for trans-lational research, John Hwa, Ph.D.,an assistant professor of pharma-cology and toxicology.

Peter Silberfarb, M.D., the Ray-mond Sobel Professor of Psychi-

atry and a pro-fessor of medi-cine, was hon-ored for his 16years of serviceas chair of theDepartment ofP s y c h i a t r y

with the establishment of the Pe-ter Silberfarb Distinguished Lec-tureship in Psychiatry.

Jonathan Ross, M.D., an associateprofessor of medicine and ofcommunity and family medicine,has been named the Almy Clin-

ical Scholar. The post is a three-year appointment that allows asenior faculty member to put ex-tra time into developing newclinical teaching programs. Itwas funded in honor of the lateThomas P. Almy, M.D., formerchair of medicine at Dartmouth.See the feature on page 32 for in-sight into one of Ross’s educa-tional efforts.

Kenneth Arndt, M.D., an adjunctprofessor of medicine, receivedthe Leon M. Goldman Memori-al Award from the American So-ciety of Laser Medicine andSurgery. The award recognizesdemonstrated longitudinal ex-cellence in performing clinicallaser research.

Eugene Lariviere, M.D., an adjunctassistant professor of pediatrics,was named Citizen of of the Yearby the Greater ManchesterChamber of Commerce. He wasinstrumental in founding theDartmouth-Hitchcock Clinicsin Manchester and Bedford.

Elizabeth Eisenhardt, a first-yearmedical student, was the solemedical student representativeat a national symposium to cre-ate strategies for increasing therole of the arts in health care.The symposium was hosted bythe National Endowment for theArts and the Society for the Artsin Health Care.

Eight first-year Dartmouthmedical students were selected asSchweitzer Fellows for 2003-2004: Joseph Dwaihy, Elizabeth Eisenhardt,Krista Heydt, Christopher Jons, Katrina

Mitchell, Shirin Sioshansi, Emily Walker, andRoy Wade. In the Schweitzer Fel-lowship program, participantsengage in interdisciplinary ac-tivities in the community that


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M E D I A M E N T I O N S : D M S

A mong the people and programs coming in forprominent media coverage in recent months

was epidemiologist John Baron. From the WashingtonPost to the Los Angeles Times and CNN to NPR,

the media covered a study he ledabout aspirin’s effect on coloncancer. Noted Newsweek: “Now,scientists say, [aspirin] may alsohelp ward off colon cancer, atleast in high-risk populations.”The San Francisco Chronicle re-ported that “Dr. John Baron of

Dartmouth Medical School said aspirin’s benefitsare real but modest.” And Reader’s Digest issued acaution: “Though aspirin is great, says Dart-mouth’s John Baron, it has risks. Talk to your doc-tor first.” See page 10 for more on the study.

A Newsweek cover story on pain quoted a DHMCexpert for insights into “small patients, big pain.”Doctors are “rethinking the treatment of acute

pain for children who go toemergency rooms for more com-mon injuries like broken limbsor cuts that need stitches. In thepast ‘you brought your kid to thehospital. They held them downand did something that hurt,and you brought them home,’

says Joe Cravero, a pediatrician and anesthesiologistwho is cowriting an American Academy of Pedi-atrics policy statement on pain relief in the ER.”

“The perils of prevention” was the headline on aNew York Times feature about some downsides ofaggressive screening practices. “‘Imaging has im-proved so much, we can find things we really don’tknow enough about,’ says Dr. William Black, a radiol-

ogist at Dartmouth. In the faceof this uncertainty, doctors saythey must err on the side of cau-tion and treat practically everytiny tumor as if it were poten-tially deadly. . . . But that meansthat widespread screening forprostate and breast cancer has

resulted in huge numbers of patients suffering theside effects of unnecessary medicine.” See page 14for a recent study on a related topic.

From Better Homes & Gardens, to the New YorkTimes, to the San Diego Union-Tribune, the wordis out that the advice to drink eight 8-ounce glass-es of water a day is all wet. A review article onthe subject last year by DMS physiologist Heinz Valtinis still getting wide coverage. BH&G wrote that“according to a study at Dartmouth, the ‘8-by-8rule,’ as it’s known among nutritionists, doesn’tappear to have any real scientific basis.” The NewYork Times said many marathoners are “overhy-

drated, having fallen for whatDr. Heinz Valtin of Dartmouthdeems a medical myth: that de-hydration is always lurking.”And in the San Diego newspa-per, “Heinz Valtin, a noted kid-ney expert from Dartmouth,[warned that] water intoxication

and even death can result from drinking more wa-ter than your kidneys can process.”

Debate in the scientific community regarding therigor of space-shuttle science was fodder for a re-cent article in the Houston Chronicle. One of theexperts who defended such work was “Jay Buckey, aDartmouth medical professor who flew on Neu-rolab. . . . Buckey said NASA did several thingsright for Neurolab, such as tailoring the flight tofit the science and not the science to fit the flight.”

“Take two recent medical anecdotes,” wrote a re-porter for the Milwaukee Journal-Sentinel. “I had

two surgeries, one on a knee andanother on a wrist, and nobodyasked me in a systematic wayhow they came out. My doctorsknow and I know, but no oneelse knows. In the same timeframe, my son had a back oper-ation at Dartmouth-Hitchcock

Medical Center, a longtime leader in systematicmedicine. . . . His results, like mine, were excel-lent, but his were fed into a real-time database,while mine went into the ether.” The director ofDHMC’s Spine Center is James Weinstein.

Ruing “a medical arms race that is spreading open-heart surgery across southeastern Pennsylvaniabut is draining the number of patients at many

emphasize values and leadership.Anthony Perrone, a third-year

medical student, was elected re-gional chair for legislative affairsof the American Medical Asso-ciation’s Organization of StudentRepresentatives.

Kim O’Hara, a graduate studentin pharmacology and toxicology,received the Society of Toxicol-ogy’s Taylor & Francis GraduateStudent Award, Metals Special-ty Section.

In the 2003 U.S. News &World Report ranking of thecountry’s 125 medical schools,Dartmouth Medical School was ranked

35th on a scaleemphas i z ingresearch activ-ity and 27th ona scale empha-sizing the per-c e n t a g e o fgraduates who

enter primary-care specialties.The rankings are based on grantfunding, reputation, test scores,and student-faculty ratios.

Dartmouth-Hitchcock Medical Centerwas named by Business NH Mag-

azine and theNew Hamp-shire Associa-tion of Cham-ber of Com-merce Execu-t i ve s a s theHealth-Care

Business of the Year for 2003.Factors considered in making theaward were impact on the indus-try and the community.

DMS’s Patient Partnership Programwas selected by the Fetzer Insti-tute as a finalist for the 2002Norman Cousins Award. Cous-

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programs, threatening patient safety,” thePhiladelphia Inquirer turned to a Dartmouthexpert on the effect of volume on surgeryrisk. “In the largest surgical volume studyever done, John Birkmeyer, chief of generalsurgery at Dartmouth, found that 4.8% ofMedicare patients died soon after bypassesin high volume hospitals. But the death ratejumped to 6.1% for bypass patients in thelowest-volume hospitals.”

The Wall Street Journal reported that rup-tured aneurysms, “a ballooned section of ablood vessel, . . . kill an estimated 18,000Americans a year—more than AIDS orbrain cancer.” They can be diagnosed with“a simple test,” but it’s not covered by mostinsurers or recommended by most doctors.Now, however, “a large new study is beingorganized by the medical schools at Dart-mouth, the University of Pennsylvania, andthe University of Pittsburgh. Initially it will

measure the prevalence ofaneurysms; a later phasewill check for a mortalitybenefit from screening.‘There i s reasonableemerging evidence sug-gesting it’s reasonable toscreen men over 60’ for

abdominal aneurysm, ‘particularly if theyhave a history of smoking, and anyone witha first-degree relative with an aneurysm,’says Jack Cronenwett, a study organizer and chiefof vascular surgery at Dartmouth.”

Noted the Miami Herald: “Blood banks arestarting to adopt new anti-germ technolo-gy. ‘Although the public is worried aboutHIV or West Nile virus, we may have to oc-casionally stand up and say in public or to anewspaper reporter, “That’s not what weshould be worrying about,”’ blood safety ex-pert James AuBuchon of Dartmouth told a recentmeeting of the government’s top blood ad-visors. ‘Share with the public what the realrisks are.’ Topping that list: germs.” AuBu-chon’s work was the subject of the cover fea-ture in the Spring issue of the magazine.

Though bioterrorism remains a subject ofconcern, “vaccinating the entire U.S. pop-ulation for smallpox in the 21st century,without signs of an attack, is a step vaccineexperts call extreme,” reported Newsday.“‘We need a policy, but that doesn’t meanthat we have a general policy to immunizelarge numbers of people,’ said Dr. John Modlin,”who chairs the federal Advisory Committeeon Immunization Practices. “Modlin, a pro-fessor at Dartmouth Medical School, saidthe vaccine is based on a live virus, andtherefore a policy must be carefully crafted.”

The Baltimore Sun wrote about a problemthat “cancer patients [call] chemo brain or

chemo curse . . . a sensethat their brains are in afog. In one study of breastcancer and lymphomapatients at Dartmouth-Hitchcock Medical Cen-ter, more than twice asmany chemotherapy pa-

tients scored in the lower impaired rangethan did patients who had radiation orsurgery. Dr. Tim Ahles, who directs psycho-oncology research at Dartmouth, founddeficits even after accounting for educationdifferences and screening out survivors withproblems such as depression and anxiety.”

Newsday reported on “arsenic’s reputationfor toxic nastiness,” saying a Dartmouthstudy shows “that even minuscule doses dis-rupt the way hormones work. . . . ‘Arsenic is

an agent of considerablepublic health concern inthe United States andworldwide,’ said toxicolo-gist Joshua Hamilton of Dart-mouth. The elementalmetal is already known tobe outright poisonous. . . .

Now, Hamilton said, ‘it’s very clear that ar-senic is a potent endocrine disrupter.’”

The London Daily Telegraph carried word ofa recent “finding that some sufferers from

temporal lobe epilepsy . . . seem to experi-ence devout hallucinations that bear strik-ing resemblances to the mystical experi-

ences of holy figures suchas St. Paul or Moses. Thistheory received a boostfrom Gregory Holmes, a pedi-atric neurologist at Dart-mouth, who says one ofthe principal founders ofthe Seventh-Day Adven-

tist movement, Ellen White, in fact sufferedfrom temporal lobe epilepsy.”

The myriad benefits of a good night’s sleepwere recently touted in the pages of Reader’sDigest. “The solutions to sleeplessness arebetter than ever, but it helps to understandthe nature of your problem, says Michael Sateia,

who directs the Dart-mouth-Hitchcock SleepDisorders Center. ‘Virtual-ly everyone has at least atransient period of insom-nia that lasts a night or afew nights.’ It could betriggered by grief, hard-

ship, jet lag, divorce, or pressures at work.But most people get over it quickly.”

The connection between sleep disturbancesand traumatic events was the subject of apiece on ABCNews.com. Another Dart-mouth sleep medicine expert, Thomas Mellman,was quoted as saying that a traumatic eventcan disturb sleep in several ways. “A personmight feel the need to be alert or on guard.And being alert is basically incompatible

with being asleep,” he said.“Also, worry and intrusivethoughts, such as disturb-ing images of what hap-pened, might interferewith sleep. . . . Similarly,there are certain startlemechanisms that can actu-

ally operate within sleep. . . . Finally, partic-ularly intense, life-threatening experiencescan affect what one dreams about.”

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