Promise – Spring 2003

CHANGE SERVICE REQUESTEDNon-Profit Org.U.S. Postage

PAIDPermit No. 1112

Memphis, TN

332 N. LauderdaleMemphis, Tennessee 38105-2794

Public Information: 1-866-2STJUDE, ext. 3306 Donations: 1-800-822-6344Visit our Web site at www.stjude.org.

St. Jude Children’s Research Hospital, American Lebanese Syrian Associated Charities and ALSAC are registered trademarks.

PromiseA publication of St. Jude Children’s Research Hospital Spring 2003A publication of St. Jude Children’s Research Hospital Spring 2003 Promise

Eagle’sWingspage 12

Eagle’sWingspage 12

Spring 2003 Promise 1

St. Jude Children’s Research Hospital was founded by the

late entertainer Danny Thomas. It opened February 4, 1962. The hospital

was created because of a promise Danny made during the depression era to

St. Jude Thaddeus, the patron saint of the hopeless.

“Show me my way in life,” Danny prayed. In return, Danny promised to build

St. Jude Thaddeus a shrine. That shrine became a hospital that would treat

children regardless of race, color, creed or their ability to pay. This remarkable

event also inspired the name of this magazine,

Promise.

St. Jude Children’s Research Hospital, Memphis, Tennessee

Features3 A Whole Lot of Lovin’ Goin’ On

Searching for a rock ‘n’ roll legend and finding a hospital

4 Two Thumbs UpThe world’s first clinic for children with cancer and ataxia-telangiectasia

8 Following the CluesUnraveling the mystery of adrenocortical carcinoma in Brazil

12 Eagle’s WingsCourage, heroism and patriotism take flight

17 Untangling Sickle CellIn search of an elusive cure

22 Fan-tastic ChallengeCompetition for the kids

Highlights2 Achievements and events

Perspective24 Ron Seggi

Broadcasting the mission

Promiseis a quarterly publication of theDepartment of Public RelationsSt. Jude Children’s Research Hospital332 N. LauderdaleMemphis, Tennessee 38105

St. Jude Children’s ResearchHospital’s mission is to find cures forchildren with catastrophic diseasesthrough research and treatment.

Hospital DirectorArthur W. Nienhuis, MD

ALSAC National Executive DirectorRichard C. Shadyac

ALSAC/St. Jude Vice President ofCommunications and Public RelationsJerry Chipman

Director of Public RelationsJudith W. Black

ALSAC Director of CommunicationsGeorge Shadroui

Editor and Publications ManagerElizabeth Jane Walker

Art DirectorJessica W. Anderson

Photo EditorJere Parobek

PhotographersSeth DixonLaura HajarAnn-Margaret HedgesEvanne NewmanJere ParobekQuad-City Times

Contributing WritersTanuja ColettaJoe HannaAlicia H. MatthewsCarrie L. Strehlau

Guest AuthorRon Seggi

Editorial Advisory BoardBonnie Cameron Leslie Davidson Pat Flynn, MD Mark Hendricks Lisa HillMarc Kusinitz, PhDPhil McCarty Carlos Rodriguez-Galindo, MDAnn Smith Sally Wiard John Zacher

PromiseA publication of St. Jude Children’s Research Hospital Spring 2003

St. Jude Children’s Research Hospital is an equal-opportunity employer. For inquiries aboutstories in this publication, call the Public Relations department at (901) 495-2125 or [email protected]. Visit our Web site at www.stjude.org/Promise. Articles and pho-tos may be reprinted with permission. ©2003.

On the cover: St. Jude patient Jacob Littrell (see article, page 12). Many thanks to AmericanFlag and Flagpole Co. for providing the flag used in this shot. Photo by Seth Dixon.

Spring 2003 Promise 32 Promise Spring 2003

Foiled againSt. Jude investigators have shown

how cooperation between influenzavirus and bacterial pneumonia infec-tions can be foiled, even if treatment isdelayed and flu virus levels in the lunghave peaked.

Jonathan McCullers, MD, of St. Jude Infectious Diseases showedthat the flu virus enzyme neu-raminidase (NA) strips lung cells ofmolecules called sialic acid. The unpro-tected cells are then vulnerable toinfection with bacterial pneumonia.But treatment with the drug oste-lamivir blocked the activity of NA andoffered protection against pneumonia.The findings appeared in the March2003 issue of the Journal of InfectiousDiseases.

The study is important becauseinfluenza and pneumonia together arethe sixth leading cause of all deathsworldwide, and the top cause of deathdue to infection.

Brain powerResearchers have discovered a criti-

cal, early step in the embryo that isrequired for proper development of thehuman brain.

That step is controlled by the prod-uct of a gene called Six3, which guidesthe formation of the embryonic part ofthe brain called the forebrain. Theforebrain is destined to contain theeyes, olfactory center, cerebrum andother structures. St. Jude scientistsshowed that the Six3 gene ensuresproper development of the forebrainby halting the activity of another genethat controls development of othermore posterior parts of the brain. Thediscovery is an important step towarddefining a critical regulatory pathwayfor normal brain development.

A team of scientists led by

Guillermo Oliver, PhD, and OlegLagutin, PhD, of Genetics publishedthe study in the February 2003 editionof Genes & Development.

Bait and switchA new immunologic “bait and

switch” technique developed at St. Jude allows researchers to use agenetically engineered protein “bait”to lure rogue immune cells to theirdeaths.

The St. Jude strategy pitted thegenetically engineered immune cellscalled T lymphocytes against a popula-tion of T cells that cause a brain dis-ease. The genetically engineered cellsreduced brain damage by destroyingthe T cells that caused the disease. Thediscovery offers hope for treating mul-tiple sclerosis, rheumatoid arthritis andother autoimmune diseases caused byT cells. The technique also may be use-ful for slowing or preventing thebody’s rejection of transplanted organsand tissues.

The research, led by TerrenceGeiger, MD, PhD, of St. JudePathology, was featured in theDecember 2002 issue of NatureBiotechnology.

Primordial GenesSt. Jude researchers appear to have

looked back in time. They have discov-ered that the Arf gene was once mod-erately effective in slowing down cellu-lar reproduction until it linked up witha more efficient set of genes to create apowerful anti-cancer response.

Arf was already known to havecancer-suppressing activity. A St. Judeteam found that Arf may have evolvedto slow the cell’s metabolism andgrowth by limiting production of ribo-somes, which guide production of all

other cellular proteins. The researchersshowed that Arf interferes with pro-duction of the RNA components ofribosomes to control protein produc-tion and cell growth.

The discovery was made byHoward Hughes Medical InstituteInvestigator Charles Sherr, MD, PhD;Masataka Sugimoto; Mei-Ling Kuo,PhD; and Martine Roussel, PhD, all ofSt. Jude Genetics and Tumor CellBiology. A report on the findings waspublished in the February 2003 issueof Molecular Cell.

Child’s playChild magazine has named St. Jude

as one of the top five children’s cancerhospitals in the United States. Therankings appeared in the February2003 issue of Child.

To be considered for the Child mag-azine survey, a hospital must belong tothe National Association of Children’sHospitals and Related Institutions.Child narrowed the field, based oneach hospital’s evaluation by the JointCommission on Accreditation ofHealthcare Organizations. St. Judereceived an overall score of 98 out of apossible 100 points during the hospi-tal’s last accreditation survey in 2000.

National awardRobert Webster, PhD, of St. Jude

Infectious Diseases recently receivedthe Twelfth Annual Bristol-MyersSquibb Award for DistinguishedAchievement in Infectious DiseasesResearch for his pivotal role in theunderstanding of the origins, evolutionand approaches for control of epidemicinfluenza virus. Webster received the$50,000 cash prize and a commemora-tive silver medallion at a dinner held inhis honor in New York in December.

Highlights

Twenty-five years ago, Donald and Anne Welsh of Drums,Pennsylvania, traveled to Memphis in search of a rock ‘n’ roll legend. Inthe process, they found a world-renowned hospital.

The Welshes came to Memphis in1978 to visit Elvis Presley’s home,Graceland. As longtime Elvis fans, theyfondly recall their visit that year asthey tried to locate Elvis’ old schooland the trauma center to which hedonated money. In the process, theyfound St. Jude Children’s ResearchHospital. After reviewing hospital publications and learning about theinstitution’s mission, the couple wasimpressed.

Today, the Welshes are still Elvis

fans and zealous advocates for thework being done at St. Jude. “You canhear about the hospital, but you haveto experience it,” Donald says. “To seethe work done at St. Jude just makesyou want to do more.”

“I don’t think there is another hos-pital on earth that does more,” addsAnne. “The love shows through in allthe employees. Everyone is so caring.They make you feel like part of thefamily.”

Several years after that initial visit,the Welshes began making monthly

contributions to the hospital. Whenthey decided it was time to plan theirestate, they picked up the phone andcalled St. Jude. That call led to a meet-ing with a St. Jude representative intheir region.

“When we met with the rep, she didnot try to point us in one direction oranother,” Anne says. “She just listenedto what we had to say, gave us optionsand took our future needs intoaccount. We have been pleased withevery aspect of St. Jude.”

Because the Welshes don’t have chil-dren, they chose St. Jude as recipient oftheir estate. At every opportunity, they

try to encourage others to considerdonating to St. Jude as well.

“The first thing people want toknow is don’t we have any family toleave our possessions to,” Donald says.“But the gift to St. Jude lets me make amark in life. I wish we had the wordsto make people know how phenome-nal the hospital is.”

To learn more about ways to give,call the ALSAC Gift Planning depart-ment at (901) 578-2081, or toll-free at(800) 830-8119, ext. 2081.�

A Whole Lot of Lovin’ Goin’ OnElvis fans find much morethan music in Memphis.

BY ALICIA H. MATTHEWS

Donald and Anne Welsh plan tobequeath their estate to St. Jude. Theyare pictured with Terre Thomas, daugh-ter of St. Jude founder Danny Thomas,and St. Jude patients (from left) BrenanRodgers and Nikki Orrell.

“To see the work done at St. Jude just makes you want to do more.”

E4 Promise Spring 2003 Spring 2003 Promise 5

ST. JUDE OPENS THE WORLD’S FIRST CLINIC

SPECIFICALLY DESIGNED FOR PATIENTS WHO

HAVE CANCER AND A RARE GENETIC DISORDER

CALLED ATAXIA-TELANGIECTASIA.

Every time Ricky Mahar goes to a checkup atSt. Jude Children’s Research Hospital, he chal-lenges his doctor to a wrestling match.

And every time, Ricky wins.Torrey Sandlund, MD, is quick to concede that

8-year-old Ricky is the undisputed thumb-wrestling champion. Each week, Ricky anticipatesthe moment when he can clasp hands withSandlund for a game of dueling digits.

“Ricky loves to thumb-wrestle, and he hasbeaten me every time,” Sandlund says. “But wehave staring contests, too, where we stare at eachother and see who laughs first. I win those; healways laughs first. So we are each undefeated inour respective areas of competition.”

The camaraderie and affection between physi-cian and patient have grown since September2002, when Ricky traveled from New York toenroll in a new protocol, or scientific treatmentplan, at St. Jude. Earlier that month, Rickylearned that he had non-Hodgkin lymphoma, acancer of the lymphatic system. Because Ricky alsohas a disorder called ataxia-telangiectasia (A-T),his body would not tolerate traditional cancertreatment. So doctors at Johns Hopkins Hospitalin Baltimore, Maryland, suggested that Ricky travel to St. Jude, which houses the world’s onlyclinic specifically designed for A-T patients who have cancer.

The one-two punchChildren with ataxia-telangiectasia (pronounced

A-TACK-see-uh Teh-LAN-jick-TAY-sha) have arare, inherited neurological disorder. “Ataxia”refers to a loss of muscle control caused by degen-eration of the cerebellum, the part of the brain thatcontrols motor function. Children with this condi-tion become increasingly clumsy, and their speechbecomes slurred. Gradually, they lose their abilityto write, talk and walk. Because their muscle con-trol progressively diminishes, most A-T patientsare wheelchair bound by age 10 and rarely livebeyond their teens. Although they have normalintelligence, they have trouble reading because ofjerky eye movements. Children with A-T alsodevelop “telangiectasia,” or tiny red spider veins intheir eyes and on exposed areas of the skin.

Tim and Lisa Mahar vividly recall the day adoctor told them that Ricky had A-T, a diseasethat afflicts about 500 children in the UnitedStates. “The doctor had never had a patient withA-T before,” Lisa says. “When he was giving usthe diagnosis and telling us about it, he had abook in front of him, reading to us about it. Hepretty much told us, ‘This is what he has. There’sno treatment; there’s no cure; end of story.’”

The couple soon learned that their son’s risk ofdeveloping a malignancy could be as high as 30percent. Their worst fears were realized when

AN

N-M

AR

GA

RE

T HE

DG

ES

A rousing game of thumbwrestling between TorreySandlund, MD, andRicky Mahar always hasthe same outcome: a victory for Ricky. Thanks to the A-T clinicat St. Jude, patients withataxia-telangiectasianow have a better chanceto vanquish cancer.

BY ELIZABETH JANE WALKER2thumbsuptwothumbsup

K

I

U

S

T


Ricky developed non-Hodgkin lymphoma. “We werecompletely shocked, because we knew that this couldhappen, but we didn’t think it would happen thissoon,” recalls Tim.

Sandlund says a cancer diagnosis is the crowningblow to most parents of A-T patients. “These familiesare already stressed to the max, going through far morethan most of us could ever imagine,” he says. “They’rewatching their kids little by little losing ground. Then,on top of that, they find out that their kids have cancer.It’s like a one-two punch.”

Fighting backBecause children with A-T are extremely sensitive to

radiation and cancer-fighting drugs, they do notrespond well to traditional cancer therapy. Until recent-ly, a diagnosis of cancer in a child with A-T meant ableak prognosis.

“A lot of doctors thought that if A-T patients weresensitive to radiation, then they were also sensitive toeverything else. So they wouldn’t treat the children, andthey’d die of the cancer. Or they’d treat them very mild-ly,” says Michael Kastan, MD, PhD, chair of St. JudeHematology-Oncology.

Kastan has been studying DNA damage in A-Tpatients for more than a decade. Using what he learnedin the lab, he began designing treatment plans that hethought patients could tolerate. Physicians around theworld began calling him for suggestions about treatingtheir A-T patients who had cancer. “I would give themadvice based on my experience with the few patients Ihad seen,” Kastan explains. “I would say, ‘please keepme informed about how they do—what toxicities yousee, and what responses you get, so that I can continueto modify the advice I give.” But the busy physiciansrarely called back. The frustrated researcher then hitupon a solution. What if St. Jude created a cancer clinicjust for A-T patients—a central location where researchand treatment could occur simultaneously?

That’s exactly what happened in autumn of 2002.“We’re willing to take any patients in the world whohave A-T and get cancer,” Kastan says. “St. Judeopened this clinic because there was a need for it. If wedon’t do it, no one’s going to, and treatment wouldcontinue to go as it’s been going—a patient here, apatient there, and no one getting enough experience toknow how to improve therapies.” The St. Jude special-ists share what they learn with hospitals around theglobe; that means children who have A-T and cancercan come to St. Jude for treatment or stay in their

hometowns. If they choose the latter option, their doc-tors will work closely with the investigators at St. Jude.

With a team of St. Jude researchers and cliniciansunited with a common goal, children who have A-Tand cancer now have a better chance for survival,observes Kastan. “I can’t think of a disease that’s moredevastating than A-T,” he says, “but we can cure thecancer in a significant number of these patients andhopefully let them live for many more years.”

Building on successLong before the new clinic opened, Kastan and

Sandlund began developing the protocol for childrenwith A-T. They knew that the clinic’s patients wouldhave unique problems that must be addressed. With ahypersensitivity to ionizing radiation, these patientsmust avoid radiation therapy and drugs that producesimilar effects. Because A-T patients have trouble toler-ating one of the cornerstone drugs used in lymphomatreatment, the investigators built in protective measuresto eliminate those problems. As Kastan and Sandlunddeveloped the protocol, they modified therapy to adjustfor other challenges as well.

The A-T protocol combines several existing St. Judetreatment plans. Each is modified to account for theunique toxic effects experienced by A-T patients. Theinvestigators included treatment plans for such diseasesas high- and low-risk acute lymphoblastic leukemia,large-cell lymphoma, Burkitt’s lymphoma, lymphoblas-tic lymphoma, Hodgkin disease and non-Hodgkin lym-phoma. Pooling their expertise, Kastan, Sandlund andcolleagues from departments across the institutionspent two years writing the protocol. “Basically, thebest chance for curing cancer in children with A-T isbased on strategies that we know work in children whodon’t have this condition,” Sandlund says. “This multi-disciplinary effort is for a very small number ofpatients, but why should they receive any less of aneffort to cure their cancer than people who have muchmore common cancers?”

Sandlund says the investigators hope to learn muchmore about the kinds of cancers that children with A-Tdevelop. The researchers also study blood samples fromA-T patients for DNA breakage, in an effort to see ifthese patients are more sensitive than other people tochemotherapy.

“The academic questions are important,” saysSandlund, “but frankly, the most important purpose ofthis protocol is to provide the best therapy we cancome up with for these kids.”

Scrutinizing genesScientists in Kastan’s laboratory at St. Jude

investigate how cells respond to stresses such as DNAdamage. Although some DNA-damaging agents cancause gene mutations, cell death or cancer, others—suchas chemotherapy and radiation therapy—are used tocure cancer. So researchers are interested in understand-ing exactly how cells respond when their DNA isaltered. If scientists can learn to manipulate the cell’sresponse to DNA damage, they might be able to create ways to prevent cancer or to make therapiesmore effective.

The gene that is mutated in ataxia-telangiectasia iscalled ATM. Children have a one-in-four chance of having A-T if both of their parents carry the faultygene. Cells from children with ataxia-telangiectasia lack the ATM protein, which leaves them extremely sensitive to radiation. Kastan and his colleagues are trying to identify a drug that will inhibit that protein.By inhibiting ATM, they may be able to make all tumor cells more sensitive to radiation. If an ATMinhibitor were given during radiation therapy for abrain tumor, for instance, the radiation would be muchmore potent.

The ATM protein is a kinase, an enzyme that signalsto other proteins by modifying them. ATM adds a phosphate molecule to the other proteins in a processcalled phosphorylation. Several years ago, Kastan discovered that the ATM gene phosphorylates thetumor-suppressor gene p53, the most commonly

mutated gene in human cancer. Scientistsin Kastan’s lab have also identified eightother proteins that are modified by ATM.All eight play roles in causing differentkinds of cancer.

Kastan and Christopher Bakkenist,PhD, of Hematology-Oncology recentlydiscovered a process that helps cells in thebody respond to DNA damage. Theresearchers found that such damage acti-vates ATM almost immediately. The ATM enzyme leaps into action, phospho-rylating other proteins that play importantroles in cancer prevention. If this processdoes not occur, then the cell cannotrespond to radiation; that is what happensto children with A-T, who lack the ATM protein.

Understanding this novel biochemicalprocess lays the groundwork for learninghow to manipulate it, Kastan says. “Thisis a really big breakthrough, because it’s

the first step in everything that happens to the cell when it’s been damaged,” he explains. “It’s a uniquemechanism for an enzyme. Out of this research, we’rehoping to find a way to activate these pathways without damaging the DNA. We expect that this discovery will lead to new therapeutic approaches andprevention methods.”

Everyone’s a winnerToday, Sandlund is decked out in a jaunty Sponge

Bob Square Pants necktie, a gift from Ricky, who is anaficionado of the underwater cartoon. Ricky dutifullyadmires the necktie, but his primary focus is on theinevitable thumb-wrestling match and an imminenthomecoming. The boy has no idea that his departuremarks the culmination of years of planning andresearch; he is unaware that his involvement in St. Juderesearch may help save the lives of other patients likehimself. No, Ricky is much more concerned with chalk-ing up another victory against his arch-rival and bestbuddy.

“I’m really going to miss Ricky and his family whenthey go home,” Sandlund says, “but it’ll be nice toknow that they’re going home because he has donewell. If Ricky was the only kid we ever treated, I wouldstill say this protocol—and all the time we have investedin it—would have been worth it.”

Ricky has won once again.�

AN

N-M

AR

GA

RE

T HE

DG

ES

Michael Kastan, MD, PhD (at right), chair of St. Jude Hematology-Oncology,and Christopher Bakkenist, PhD, also of Hematology-Oncology, have discov-ered a process that helps cells in the body respond to DNA damage. Theresearchers expect that the discovery will lead to exciting new therapeuticapproaches and prevention methods.


p53

In 1987, Raul Ribeiro, MD, fin-ished his postdoctoral training at St. Jude Children’s ResearchHospital and returned to his homein Brazil. During his St. Jude fellow-ship, Ribeiro had treated childrenwith many types of cancer. But whenhe returned to Curitiba, several ofhis young Brazilian patients had akind of cancer he had not encoun-tered during the years he spent inMemphis.

The Brazilian children hadadrenocortical carcinoma (ACC), arare tumor that grows on the adre-nal gland located at the top of thekidneys. “Children with ACC werecoming to me in large pro-portions,” says Ribeiro, whohas been director of the St. Jude InternationalOutreach program since1997. “In three years atSt. Jude, I hadn’t seen

any ACC cases. I was seeing six orseven in this small part of Brazil injust one year. I thought to myself, Iknow there is something abnormalhere.”

Possible culpritsIn southern Brazil, the incidence

of ACC is 10 to 15 times higherthan in other parts of the world. Atfirst, Ribeiro thought that the mostlikely explanation for the ACCprevalence was Li-Fraumeni syn-drome. Members of families withthis syndrome have an especiallyhigh risk of developing many kinds

of cancer. But after conductingcareful clinical histories

of Brazilianpatients with

ACC, Ribeirofound that the

families did not

have histories of cancer. In 1990, hesent tumor and blood samples to St. Jude to test the function of atumor suppressor gene called p53.

When cells grow, develop, com-plete their mission in the body anddie, they are controlled by severalproteins and genetically determinedpathways. One of these regulators isthe tumor suppressor gene p53,which regulates cell survival anddeath. “In general, p53 is present inall cells controlling growth, develop-ment and cell fate,” Ribeiroexplains. A mutation in the p53gene increases the likelihood of hav-ing ACC. The tests at St. Judeshowed the p53 function was nor-mal. “Nobody believed that we hada p53 mutation,” says Ribeiro.

“I had two strikes against me,”he continues, “but we sequenced thep53 gene in 1994 just to makesure.” They subsequently discovered

CluesFOLLOWINGTHE

BY CARRIE L. STREHLAU

Why are children in southern Brazil more

susceptible to a rare type of cancer than

children in other parts of the world?

St. Jude researchers and clinicians spend

more than a decade unraveling the mystery.St. Jude researchers have been working closely with BonaldFigueiredo, MD, PhD, of the Center for Molecular Genetics andCancer Research in Brazil.


that a p53 gene mutation had occurredafter all, but that it had occurred on anew location on the DNA.

“Ninety percent of the mutationsoccur in the DNA binding domain, sopeople have not traditionally botheredto look at the outside areas,” saysGerard Zambetti, PhD, ofBiochemistry. This mutation hadoccurred outside of that bindingdomain.

Gathering evidenceWith the new information, Ribeiro

and Zambetti called Richard Kriwacki,PhD, of Structural Biology. In 1999the three men began collaborating todevelop a genetic explanation for thespecific type of ACC occurring in thechildren of Curitiba. Kriwacki identi-fied a previously unknown defect inthe structure of the p53 protein thatmade it fall apart at certain pH levels,ultimately leading to the onset ofACC. The collaborators publishedtheir findings in the journal NatureStructural Biology in 2002, and arecontinuing to follow up with morestudies of the p53 protein.

“One of the unique features of this particular case is that very oftenwhen people have mutations to p53,they develop a wide variety of differ-ent cancers,” Kriwacki says. “In thisparticular case, the mutation is associ-ated with one type of cancer. By look-ing at this mutation, we have anopportunity to get clearer insights intothe molecular pathways leading to thedevelopment of cancer.”

Researchers at St. Jude are closingin on a probable explanation for thetumor development. “There is a pH-dependent defect in the mutant pro-tein,” Kriwacki explains. “So, it sug-gests that in adrenal cells during earlydevelopment, certain changes—bestdescribed as cellular remodeling—occur in the adrenal gland. Thisremodeling may cause the environmentto be slightly basic or may elevate tem-perature slightly. There has to besomething special about the adrenalgland to explain why only these cells

develop into tumors.”“The p53 protein consists of 393

amino acids,” Zambetti adds.“Change just one and you get adrenalcancer. That’s what’s remarkable aboutthis mutation.”

The p53 mutation identified by theSt. Jude team increases children’schance of developing adrenal cancer—and only adrenal cancer—by 300,000fold, according to Zambetti. “This isthe first inherited p53 mutation thatgives rise to a specific tumor type,” hesays. Zambetti and his colleagues arecurrently exploring the possibility thatanother p53 mutation outside of theDNA binding domain may be respon-sible for a rare form of brain tumorthat seems to have an inherited com-ponent. “We don’t have an answer yetto this specific case, but we’re workingon it,” he says.

Early apprehensionThe information gleaned from

St. Jude researchers is helping clini-cians already. Physicians in Curitibaare now more alert to the symptomsof ACC and can detect them earlier

than they could in the past. “Now thatthey know there’s a genetic link,they’re tracking all of the children inthese families that have the mutation,”Kriwacki says. For the past two years,children at risk for adrenocortical car-cinoma in Curitiba have been screenedand monitored regularly for earlysymptoms of the disease.

Physicians have used the new infor-mation to develop treatment plans anda screening method. They closelyobserve ACC patients’ siblings to see ifthey exhibit signs of cancer; if symp-toms occur, they begin treatmentimmediately. “We now have more than70 patients we are following who havetested positive for a mutation but havenot developed the cancer yet,” Ribeirosays. Staff members at the clinic inCuritiba have seen more than 100patients with ACC.

The St. Jude researchers have beenworking closely with BonaldFigueiredo, MD, PhD, of the Centerfor Molecular Genetics and CancerResearch in Brazil. The discovery link-ing a p53 mutation with ACC hashelped Figueiredo and his staff identifythe mutation in many relatives of ACC

patients. “The most important contri-bution of this research is the possibilityof a cure we can now offer to childrenwho test positive for the mutation butdo not have ACC and who areenrolled in our surveillance program,”says Figueiredo, who has tested morethan 600 individuals for the mutation.Figueiredo says he believes that ACC-related deaths will decrease because ofthe new surveillance program.

Figueiredo says the infrastructure ofhis institution has improved throughassociation with St. Jude, and he citesnumerous scientific and trainingopportunities that have resulted fromthe involvement. Videoconferencinghas been one important window ofresearch communication between St. Jude and Brazilian researchers. Byusing video technology, the colleaguescan collaborate almost as easily as ifthey were sitting in a room together.Ribeiro also shares his expertise in per-son and on the phone. He travels toCuritiba twice a year to visit the centerand give lectures. And physicians fromaround the world frequently call himfor consults about their patients whohave ACC.

Ribeiro says researchers are nowexploring why ACC is prevalent insuch a small area of the world. “Theregion in Brazil in which this is fre-quent is not the entire Brazilian area,”Ribeiro says. “We are trying to see ifwe can figure out if there are environ-mental or other reasons for the prevalence.”

Carlos Rodriguez-Galindo, MD, ofSt. Jude Hematology-Oncology is alsoleading an effort to create a multi-institutional protocol with the

Children’s Oncology Group for chil-dren in both the United States andCuritiba who have ACC. In additionto treating children with this raretumor, researchers will study the biolo-gy of the tumors and the incidence ofthe different types of p53 mutations,identifying any similarities or differ-ences that appear in patients from eachcountry. Rodriguez-Galindo predictsthat the protocol will begin sometimein 2003, and may eventually expand toinclude children from other areas ofsouthern Brazil, as well.

Joining forces, saving livesA child in Paris, France, was recent-

ly found to have the mutated p53gene, so researchers suspect that theproblem may extend far beyond thegeographical boundaries of southernBrazil. As St. Jude researchers expandtheir focus to look outside the DNAbinding domain, they may find thatthe mutation occurs more frequentlythan they had expected. To addressthis possibility, St. Jude has establishedan International Pediatric AdrenalTumor Bank, which allows researchersto access samples from around theworld and screen them for p53 muta-tions and other genetic alterations.

By collaborating to attack a prob-lem, researchers in the InternationalOutreach program, the HartwellCenter for Bioinformatics andBiotechnology and other St. Judedepartments are ensuring a brighterfuture for Brazilian children withadrenocortical carcinoma. Zambetti ispleased that interdisciplinary team-work can have such far-reaching con-

sequences. “Our work is making a dif-ference,” he says. “All through mygraduate training and postdoctoralwork, my research has been focusedon trying to figure out how thingswork using cell lines we can grow inthe lab. Going from growing cell linesto actually helping kids...that’s themost rewarding part.”

Translational research—the abilityto move discoveries from the laborato-ry to the bedside—is one of the hall-marks of St. Jude. In unraveling thep53 mystery, researchers and clinicianshave shown how collaborations cansave the lives of children in other partsof the globe who may never evenknow about St. Jude Children’sResearch Hospital.

“This project is sort of amazing notonly in the scientific sense, but becauseit really exemplifies the mission of thehospital,” Kriwacki says. “The fullresources of this institution have beenbrought to bear on the basic under-standing of the origins of the diseaseand the effort on how to cure diseasesbetter in the future. It’s really been anamazing opportunity.”�

“The p53 protein consists of393 amino acids. Change justone and you get adrenal cancer.That’s what’s remarkable aboutthis mutation.”

SETH

DIX

ON

Stalking the gene that causes adrenocortical carcinoma in Brazilian children are threesuper-sleuths (from left): Gerard Zambetti, PhD, of Biochemistry; Raul Ribeiro, MD, ofInternational Outreach; and Richard Kriwacki, PhD, of Structural Biology.

Bonald Figueiredo, MD, PhD, of theCenter for Molecular Genetics andCancer Research in Brazil poses withpatients who have benefited from theSt. Jude research: Erick Quadra (topphoto) and Kelly Felde and her daugh-ter (bottom photo). Now 26 years old,Felde inherited the p53 mutation fromher father and passed it on to herdaughter, who is now in the ACC sur-veillance program.


When he’s wearing his full BoyScout regalia, Jacob Littrell’s chest is coveredwith a kaleidoscopic array of badges. Eachemblem represents a skill that Jacob hasacquired or a challenge that he has surmounted.With every accomplishment, the 17-year-oldfrom Iowa has exhibited grit and determination,leadership and selflessness.

But Jacob Littrell’s most impressive badge ofhonor is not emblazoned on his uniform’s sash.It’s imprinted on his heart.

“Be Prepared” is the scout motto, and onethat Jacob has embraced since kindergarten,when he joined the organization as a Tiger Cub.As he moved through the ranks of scouting—from Tenderfoot to Second Class, First Class toStar to Life—he learned to embody that motto,even earning a “Scholarship” honor badge forhis academic preparedness. Jacob camped in therain; hiked rocky trails; climbed high moun-tains. He mastered skills to help him safeguardthe environment and enhance his community.But when the teen learned that he had cancer,“Be Prepared” assumed a new meaning.Although the diagnosis took him by surprise,Jacob kept his focus, marshaled his innerreserves and persevered.

On my honor…Jacob, his parents and his 13-year-old sister,

Lauren, live in a small town—the perfect placefor a young man who loves to ride dirt bikes,work on car motors, canoe, fish, wage paintballwars and rappel off 300-foot cliffs. Bolstered byhis family, friends, church and scouting involve-ment, the lanky, 6-foot-tall teen is a role modelfor his friends, acquaintances and other scouts.

One day in the spring of 2001, Jacob ran amile in gym class. That evening, his right hipbegan to hurt. A few weeks later, his hip againached after a run. When Jacob visited the doc-

tor, an X-ray revealed a tumor. A biopsy indi-cated that the high school freshman hadosteosarcoma, a type of bone cancer. Jacob’saunt and uncle suggested that he visit the St. Jude Children’s Research Hospital affiliatesite in Peoria, Illinois. There, John McCallister,MD, sat down with Jacob and his parents, Jeffand Carol Littrell, and told them what toexpect.

“He was very honest and truthful aboutwhat Jacob’s treatment would probably be,”recalls Carol. “He talked to Jacob like he wascapable of understanding. The parents areimportant at St. Jude, but you can tell that thekids are the most important thing to the peoplewho work there. I was impressed with that.”Jacob was impressed, as well. “We found outabout St. Jude, and it was the way we wantedto go right from the get-go,” he says. Soonafterward, the family drove to Memphis so thatJacob could have a complete evaluation andbegin chemotherapy. After undergoing threemonths of chemotherapy, doctors at St. Juderemoved the tumor, as well as several inches ofJacob’s femur and his hip joint.

“His hip is now made out of cobalt, chromeand titanium,” explains Carol. “He’s the bionicman. He even sets off alarms at the airport!”

I will do my best…The young outdoorsman spent six grueling

weeks trapped in a body cast. After removingthe tumor in Jacob’s leg, doctors decided toremove a nodule in Jacob’s left lung. So onSeptember 11, 2001, as a numbed nationquaked from terrorist attacks, Jacob—still inthe body cast—traveled with his parents downthe deserted highways to Tennessee. After thatoperation, Jacob continued chemotherapy at theSt. Jude affiliate in Peoria for another eightmonths. Then, once again, the Littrells receiveddisturbing news: more nodules had appeared in

CO

UR

TESY

OF TH

E Q

UA

D-C

ITY TIM

ES

14 Promise Spring 2003

Jacob’slung. A secondoperation in Juneof 2002 revealed malig-nant cells. That meantanother six months ofchemotherapy.

“A thoracotomy is tough,” sayshis mother about the two lungoperations. “Six months later, hewas still sore from them. For thelongest time, he couldn’t give me abear hug because it hurt too bad.”

For the past two years, Jacobhas endured multiple operationsand countless infusions ofchemotherapy drugs. How has hecoped with the uncertainty and thepain and the sickness?

He has helped others. Jacob Littrell has planned, exe-

cuted and completed an ambitiousservice project that honors localIowans who served in the U.S.armed forces.

To do my duty…The highest rank a Boy Scout

can achieve is the Eagle designation.Fewer than 4 percent of all scoutsattain that rank. To become anEagle Scout, a boy must exhibitleadership and citizenship skills,high ethics and a working knowl-edge of the outdoors. After pro-gressing through the levels of scout-ing, Eagle candidates must havecompleted at least 21 merit badges.Before his illness, Jacob already hadearned more than 30. The onlyobstacle blocking his way was theservice project, which is intended toprovide Eagle candidates with an

opportu-nity to demon-strate their leadershipand organizational skills.

When he began investigatingpotential service projects in hishometown, Jacob learned thatmembers of American Legion Post 347 had been searching forsomeone to help them identify theveterans who were buried in thelocal cemetery. It sounded like asimple but time-consuming task.“Once I found that project, it just seemed right,” recalls Jacob.

“We had a list ofveterans’ names, and I

thought that we weregoing to go out there and

see which ones had markersand which ones didn’t; then

we would just order the num-ber of markers we needed.”Wrong.The project quickly assumed a

life of its own. Armed with a list ofveterans provided by the AmericanLegion, Jacob and his dad visitedthe cemetery, which includes nearly2,200 civilian and military graves.Jacob immediately realized that thecemetery had a chaotic record-keep-ing system. Vandals had moved orstolen many of the markers.Strolling through the grounds, theLittrells found markers for veteranswho were not on the list. “Wewalked out into that cemetery andthought, “Holy moly, there are so

many stones!” recalls Jeff.“And the plot maps theyhad were very outdated andhard to understand.” Jacob told his father,“We’ve got to come upwith our own map.” Sothey divided the 25-acrecemetery into 49 sectionsand created a detailed mapof the grounds. Realizingthat the local veterans’

records were incomplete, Jacobasked his father to help him withresearch. While Jacob was in

school, his father scoured recordsin the local Veterans Affairs office.He pored over 22,557 entries, look-

ing for veterans who were sup-posed to be buried in that ceme-tery. “It was overwhelming,”recalls Jeff. “We found names thatdidn’t coincide with anybody’srecords.”

Jacob also called upon hisfriends and fellow scouts to help.He handed dimes to the workers,and instructed them to scrape themoss off cemetery stones so thatthey could read the inscriptions.Some of the stones only protrudeda few inches out of the ground, sothose had to be raised. “I bet wehave walked through that ceme-tery 200 or 300 times,” says Jeff.“Many of those times, Jake wouldbe on crutches.”

Gradually, Jacob and his teambegan to make progress. As aresult, Jacob identified 80 veter-ans who had not been previouslyidentified. Today, the cemeteryand the American Legion havenew maps showing where eachveteran is buried, plus databankscontaining detailed informationabout each person’s servicerecord. Jacob also expanded hisefforts to encompass anothersmall cemetery nearby.

To God and my country…Because of Jacob’s hard work,

the members of the AmericanLegion post have learned that thetwo cemeteries contain veterans ofconflicts dating back to the BlackHawk wars of the 1830s, theCivil War and the Mexican-American War.

Tom Bloomingdale of theAmerican Legion is amazed at the

scope of Jacob’s achievement.“Jacob went further than we everthought he would go,” saysBloomingdale. “He put 800 to1,000 hours into this project inbetween his cancer treatments. Hehas been an inspiration to every-one.

“Jacob carried it to completionunder the most adverse conditionsimaginable,”Bloomingdalecontinues.“Now every-thing isupdated anddocumentedon the com-puter. Someonewithin theAmerican Legion can carry iton from here.”

Bloomingdale and his comradeswanted to find a way to thank theboy who had shown such courageand strength while waging his ownwar with cancer. So last Novemberthe veterans held a special ceremo-ny to honor the young warrior whohad been such an inspiration. AsJacob quietly accepted his award,every veteran in the room stoodand saluted a fellow hero.

And to obey the Scout LawJacob does not perceive his proj-

ect as heroic or extraordinary. Hesays he never considered the possi-bility of abandoning the Eagle proj-ect when he got sick. Fortunately,he had already completed the Eaglerequirements that demanded out-door skills and physical agility. “Iknew I’d get the project done,”says Jacob. “I just knew it wouldtake a little bit longer than usualbecause I was dealing with other

CO

UR

TESY

OF TH

E Q

UA

D-C

ITY TIM

ES

Jacob places a gleaming, newmarker at a veteran’s grave.Thanks to Jacob, members ofthe local American Legion postnow have detailed and valu-able information about theircomrades who are buried inarea cemeteries.

Three days before he discovered that he had osteosarcoma, Jacob demonstratedhis athletic prowess by leaping from a tower and rappelling to the ground.Rappelling is only one of the many skills Jacob mastered en route to earninghis Eagle Scout designation.



things that were more importantat the time. I knew that the cancer was only a temporary thingand that this project would get finished.”

Jacob is pleased that his com-munity has responded positively tohis efforts, and he feels a sense ofaccomplishment at having helpedothers. “I think this project givesall the veterans their due,” heexplains. “There were so manyveterans buried in that cemeterywho didn’t have markers, and itwas an injustice to them. Thisproject just kind of gives them therecognition they deserve.”

In earning the Eagle Scout des-ignation, Jacob joins an elite groupthat includes former PresidentGerald Ford; William McCool,

pilot of the space shuttleColumbia; actor Jimmy Stewart;TV commentator Walter Cronkite;Togo West Jr., former secretary ofthe Army and secretary ofVeteran’s Affairs; and director/pro-ducer Steven Spielberg. But Jacobsays he’s not interested in fame;he’s more concerned about collegeand career. “Becoming an EagleScout finishes the scouting chapterin my life,” he observes. “I startedout at the bottom and I prettymuch worked my way up, learn-ing a lot about organ-ization and lead-ership andstuff likethat. It willgive meadvan-

tages when I apply for college orjobs later in life.”

“I’m so proud of Jacob,” saysNajat Daw, MD, the physicianwho treats Jacob at St. Jude. “He’svery bright and strong-willed.”Jacob’s parents concur with thatdescription. They watched himplan the project, delegate authorityand follow the task to completion.“He is our hero,” says his father.“A very brave young man. Hedoesn’t complain; he just gets itdone.”

“Be Prepared.” According tothe Boy Scout Handbook, thismotto implies that scouts should

be ready in body and mindto meet the struggles and

challenges of life. Inearning his wings,Jacob Littrell has

shown us all howto fly. �

Krista Mills is obsessed with baby dolls. She hasscores of them sitting in bookcases and crowdingher bed, many tumbling onto the floor. “WheneverI get my allowance, the first thing I want to get is

a new doll,” says the grinning 14-year-old. “I love to holdthem.”

As a collectors’ catalog featuring a new line of realisticdolls seizes Krista’s attention—she has her heart set on anewborn wrapped in a soft, pink blanket—her mother staresat her from across their kitchen. Wendy Mills’ wish is simplyfor her own baby to grow into a healthy woman, free of thesickle cell disease that has plagued Krista since birth.

She has reason to be optimistic.St. Jude Children’s Research Hospital, where Krista is a

patient, has been awarded a $9 million federal grant thatmay help scientists discover sickle cell’s elusive cure.


LAU

RA

HA

JAR

A $9 million federal grantmay help St. Jude scientistsreverse the effects of a tinymutation that causes sicklecell disease.

UntanglingBY TANUJA COLETTA

Sickle Cell

Jacob (at far left) has been involved in scouting since the first grade. As heprogressed through the ranks, he has participated in countless adventures,such as this journey down the Mississippi River, which occurred when hewas in the eighth grade.

Winfred Wang, MD, director of the St. JudeHematology division, has been giving hydroxyureato 6-year-old Lakia Baldwin, with great results.“Lakia used to feel sick all the time,” says her mother. “Now she doesn’t even get a headache.”


A five-pronged approachAlthough St. Jude is best known

for its advances in research and treat-ment of pediatric cancer, the firstgrant ever awarded at the hospitalwent to a sickle cell researcher. Thatwas in 1962, the year the hospitalopened its doors. Today, St. Jude isone of 10 Comprehensive Sickle CellCenters in the country to receive amulti-million-dollar, competitive five-year grant from the National Heart,Lung and Blood Institute. St. Jude isalready home to one of the nation’slargest sickle cell research centers.The grant will allow expansion of theinstitution’s research and outreachefforts and collaboration with othersickle cell centers.

“This will be our first attempt to

build a national clinical trials net-work among the ComprehensiveSickle Cell Centers,” says WinfredWang, MD, director of the St. JudeHematology division and the hospi-tal’s sickle cell program. “Thisapproach has been successful inimproving outcomes for childhoodcancers but has not been establishedfor sickle cell disease.” A nationalclinical trials network will giveresearchers access to a much largerpool of patients and information thanever before, as large numbers of chil-dren and adults with sickle cell dis-ease are treated uniformly across thecountry.

St. Jude researchers plan to targetsickle cell disease with studies in fivemain areas: combination drug thera-

py, bacterial infection, stem cell trans-plantation, gene therapy and themolecular biology of hemoglobindevelopment. “If we have success inany or all of these areas, there ispotential for tremendous benefit forall sickle cell patients, children andadults,” says Wang.

Tragic typoAn inherited disorder of the red

blood cells, sickle cell disease is like atypo with tragic results. The disorderarises from a single incorrect letter inthe 60,000-letter gene for hemoglo-bin, the oxygen-carrying protein thatgives red blood cells their color.Normally round and soft, cells affect-ed by this mutation resemble micro-

scopic boomerangs. The misshapencells hook together, forming longrods that clog small blood vesselsand deprive organs and tissues ofoxygen-carrying blood. The bottle-neck leads to episodes of severe pain,organ damage and even death.Regular blood transfusions are theoldest form of therapy, but theymainly combat symptoms, not theunderlying disease. Bone marrowtransplants have cured sickle cell dis-ease in about 200 patients, but theprocedure is not a universal optiondue to a lack of suitable donors.

About half of the patients withsickle cell disease live beyond age 50,and Krista plans to be a member ofthat group. She is one of 72,000Americans with the disease, whichdisproportionately affects people ofAfrican, Hispanic, Middle Eastern,Mediterranean and Indian descent.She inherited one copy of the mutat-ed gene from her mother and onefrom her father. When both parentscarry the trait—a single copy of themutated gene—each of their childrenhas a one-in-four chance of develop-ing the disorder. Krista’s younger sis-ter Katlyn was born with the trait,meaning that she will likely neverhave sickle cell symptoms but couldpass the trait to her children.

Early detection is importantbecause treatment could ward off thepainful symptoms. More than 40states now have a sickle cell screen-ing test for newborns. Wendy Millswishes Krista had been tested whenshe was born. The couple didn’t findout Krista had sickle cell disease untilshe had her first crisis at 2 years ofage. “She was getting very sickand lethargic,” says Wendy.“She would scream inher sleep. The painwas excruciating.”Krista had one ortwo pain episodes ayear. Then, justbefore her eighthbirthday, she sufferedher first stroke, a dev-astating complication of

sickle cell disease. The stroke weak-ened the left side of Krista’s body,causing her to lean to one side andlimp. A couple of months later, a sec-ond stroke left Krista weak on bothsides. The strokes caused seizures,damage to her eye muscles and some

loss of cognitive abilities. Kristabegan wearing braces on her legs forsupport.

The Millses were referred to the St. Jude Sickle Cell Program. Aftermuch discussion—the family hadserious concerns about blood transfu-

LAU

RA

HA

JAR

Grant Steen, PhD, of St. JudeDiagnostic Imaging is studying the brainsof hundreds of healthy people, from new-borns to octogenarians. He hopes that byexamining normal brains, he may betterunderstand the brains of children withsickle cell disease.

Sickle cell patients have a 250-foldhigher risk than normal of having strokes.Steen is using a form of magnetic reso-nance imaging (MRI) to demonstrate sub-tle changes in the brains of many young

sickle cell patients with damaged bloodvessels. The damage may be caused bythe high rate of blood flow through thebrain as the body tries to compensate fora lack of oxygen-carrying red blood cells.Sometimes the body adapts by dilatingarteries or expanding bone marrowaround the brain. Often, the adjustmentsstill do not allow enough oxygen to reachthe brain.

Sickle cell disease provides a goodmodel for studying stroke, which oftenkills adults.

“The problem with studying stroke inadults is that by the time we reach oldage, we have a host of other ailments thatmask what’s happening with the disease,”Steen explains. “We can better understandthe idiosyncrasies of pediatric stroke,which is essentially the same process asin adults, since stroke is likely the onlybrain illness they have.”

Battling Brain Damage

Grant Steen, PhD, obtained these MRI images during a study of young patients withsickle cell disease. The one at left shows the brain of a healthy child. The image atright offers a glimpse of a severe compensation for sickle cell disease: the bone mar-row of the skull has proliferated to produce more red blood cells, and this may besqueezing the patient’s brain.

This MRI image shows thebrain of a 3-year-old sick-le cell patient who had astroke. The pale areas atright show damage tothe brain. The bright-ness indicates that thereis too much water in this

part of the brain, proba-bly because cells in the

gray matter have died.

After suffering two strokes because of sickle cell disease, Krista Mills had to cope with the loss of somecognitive skills. She is making progress through an expanded resource program at her school. Becauseteachers are often unaware of sickle cell disease’s effects on learning, St. Jude has hired a teacher towork with school officials and parents on issues relating to the disease. The position is one of the firstof its kind in the nation. St. Jude is also one of the largest publishers of sickle cell education literature,with a national and international distribution of more than 9,000 items annually.



sions—Krista was placed on hydrox-yurea, an anti-cancer drug recentlyapproved by the Food and DrugAdministration for use in adults withsickle cell disease and frequent paincrises. Trials with children andinfants are showing promise, too.“We knew it was experimental, butwe were hopeful,” says Wendy. “Sofar, it has been a miracle for us.”Krista has not suffered any majorpain crises or strokes since startingher daily dose of pills.

Hydroxyurea increases the body’sproduction of a type of so-called fetalhemoglobin, which counteracts theeffects of sickle hemoglobin withinthe red blood cells and reduces thedisease’s severity. Wang, who has ledSt. Jude studies on hydroxyurea, isinterested in combining the drug withmagnesium. He hopes the combina-tion will further ease symptoms anddelay or prevent organ damage to thespleen, kidneys and brain. By age 3,most children with sickle cell diseasedo not have functioning spleens tohelp fight infection. The consequencemay be a fatal bacterial infection,which in the past has been the lead-ing cause of death in children withsickle cell disease.

Looking deeper“Sickle cell patients are a

curiosity,” says Elaine Tuomanen,MD, chair of St. Jude InfectionsDiseases. “They are at a 300-foldincreased risk of dying of pneumo-coccal disease, yet no one knowsexactly why.”

Tuomanen is studying the antibi-otic tolerance level of sickle cellpatients, who are often on the infec-tion-fighting drugs for many years.Long-term antibiotic use may eventu-ally lead patients to resist the drugs’benefits and succumb to bacterialinvaders, especially pneumococcus.Because sickle cell patients are onantibiotics for so long, the deadlybacteria learn to out-fox the drugs.

“Bacteria divide every 20 minutes, sothey can rethink their game planevery time they launch a new attack,”says Tuomanen. “If you give themlong enough, they will certainly figureout a method that works.Unfortunately for sickle sell patients,it’s like they are wearing a red flagtelling the bacteria to come takeadvantage of them.”

Tuomanen models the scenario inher laboratory to help understandwhy sickle cell patients are at a high-er risk for infection than healthy peo-ple. Other St. Jude researchers arestudying hemoglobin development atthe molecular level. Sickle cell disease

was the first disease for which scien-tists knew the exact genetic defectthat caused the malady, but scientistshave been unable to translate thatknowledge into a cure. JohnCunninghan, MD, of St. JudeHematology-Oncology, predicts thatnew advances, especially in the studyof globin genes, will have greatimpact on sickle cell treatment duringthe coming decade. “Specifically, thelong-term interest of my lab is tounderstand the switch of gamma glo-bin to beta globin,” he says. Duringnormal development, the genes cod-ing for gamma globin, the kind pro-duced by fetuses, are switched off

soon after birth, and the body beginsproducing adult beta globin. “In peo-ple with sickle cell disease, with thisswitch, the sickle cell proteinbecomes predominant. We are testingapproaches to reverse this switch.”The answer could provide clues forthe cure of the related blood disease,beta-thalassemia.

Transplants to the rescueFor now, bone marrow transplants

offer the best hope for a cure. Thefirst bone marrow transplant to curesickle cell occurred at St. Jude in1982 when a leukemia patient under-went the procedure and was cured ofboth diseases. During a transplant, apatient’s bone marrow—the spongytissue in the center of bones—isdestroyed and replaced with healthydonor tissue. But often, perfectlymatched donors are not available.Even if donors are available, trans-plants are risky: patients may developgraft-versus-host disease, in which thetransplanted tissue attacks thepatient’s cells.

St. Jude scientists are experiment-ing with a way to sidestep those com-plications and allow unmatcheddonors to supply stem cells for trans-plants. Produced by bone marrow,stem cells are undeveloped cells thatmature into immune and blood cells,including, in some cases, mutated

sickle cells. A technique pioneered byRupert Handgretinger, MD, PhD,director of Stem Cell Transplantation,isolates healthy stem cells from thecells that can trigger graft-versus-host disease. The method allowspatients to receive a higher concen-tration of stem cells and better toler-ate the transplant than they wouldwith traditional bone marrow transplantation.

Sickle cell patients may also bene-fit from new transplant methodsusing stem cells in blood from theumbilical cord and placentas of new-borns. In 2000, St. Jude patientKhadi Toure was the first child in thecountry to receive umbilical cordblood from a sibling to treat sicklecell disease.

However, researchers are alreadylooking beyond these therapies to atechnique that could rival all othersfor a cure: gene therapy.

New hope for curesStill highly experimental, gene

therapy is designed to replace thedefective gene for hemoglobin. Genetherapy may one day allow doctorsto insert a normal gene into a cell toeradicate the disease. One possiblegene therapy approach is to perma-nently increase the level of “good”hemoglobin in the body to overpowerthe sickling type. “A possibility we

are studying is to take the patient’sown blood stem cells, to correct themand to place them back into thebody,” says Derek Persons, MD,PhD, Hematology-Oncology. Virusesare adept at injecting their own genesinto cells, so Person and his col-leagues are using viruses as “carriers”to insert a healthy hemoglobin gene.The viruses are gutted of their harm-ful genetic codes and are replacedwith the healthy gene. Instead ofattacking the cell and causing harm,the virus instead injects the healthygene into the diseased cell.

“It would still have its risks so it’snot the first thing you try out of thebox,” says Persons, “but it’s anoption, especially for those withoutany other recourse.”

Persons is encouraged by the col-laboration among St. Jude depart-ments and the new networks growingbetween the hospital and other sicklecell centers. “We’re coming at thisfrom different aspects,” he says.“You never know where the answerwill come from. At the end of theday, it might very well be that theanswer lies in a combination of theseapproaches.”

Krista Mills is counting on it.“I’ve always had a strong sense offaith from my parents and my grand-mother that I can do anything,” shesays. “I choose to look at that side ofthe rainbow and focus on what I cando, not on what I can’t. For me, thegreatest thing would be to grow upinto a good girl like my mother.”�

St. Jude patient Khadi Toure, 11, pictured with her father, Abdoulaye,was the first child in the country to receive umbilical cord blood froma sibling to treat sickle cell disease.

Instead of being round and soft, sickle cells look like microscopic boomerangs.The misshapen cells can cause severe pain crises, organ damage and even death.

SETH

DIX

ON

GO

PAL M

UR

TI

22 Promise Spring 2003 Spring 2003 Promise 23

Urban asked all in attendance to dowhat they could to raise money for St. Jude through a friendly competitionamong fan clubs.

This Australian singer/guitaristburst on the country music scene in2000. Urban’s performance earned himthe Top New Male Vocalist Award atthe 2001 Academy of Country MusicAwards and established him as a risingstar. The year 2000 also markedUrban’s first visit to St. Jude. Hetoured the hospital as part of the 2000Country Cares seminar along withother artists and hundreds of represen-tatives from country radio stationsaround the country. The mission ofDanny Thomas, to ensure that “nochild should die in the dawn of life,”touched Urban’s heart.

“One trip to St Jude will leave youwith no doubt that progress is beingmade,” Urban says. “There is nogreater contribution to make in ourlives than to our children, the future.In sharing their findings with hospitalsall around the world, St. Jude contin-ues to help not just the kids who arethere but children and their familieseverywhere. This is why we initiatedthe Fan Club Challenge. Awareness isthe key to continue and grow the sup-port we all have for St. Jude.”

Enthusiastic warriorsCountry entertainer Toby Keith’s

fans, or “warriors” as he calls them,threw down the first gauntlet in theFan Club Challenge. The day afterUrban made his challenge, Keith’s fansraised $2,705 through an auction ofthe singer’s memorabilia at the openingday of Fan Fair.

A flurry of activity followed. Fanclub Web sites began carrying the chal-lenge to all corners of the countrymusic world. Ideas on how to meet the challenge poured in. Calendar andT-shirt sales, silent auctions, sales offood by individuals and businesses—even collections of aluminum cans—were all ways that groups rallied around the cause.

Fans of country artists TracyLawrence, Tommy Shane Steiner, BillyRay Cyrus, Andy Griggs, Bryan White, Gary Allan, Wynonna Judd and more have joined in the challengeto see whose fan club can raise themost funds.

Urban fans respondOne of Urban’s fans opted to sell

Keith Urban calendars that featuredconcert photos submitted by the fans.Response was tremendous, not just in

terms of the photographs, but in indi-viduals wishing to help defray produc-tion costs so the total profit from thecalendar sales would go to St. Jude.

So far, the Urban calendar hasraised $6,165 for the hospital. Thatputs Urban’s fan club in the lead withmore than $21,000 raised, including a $10,000 donation from an anony-mous fan.

“I am very proud of how the fanshave responded; how giving they haveall been,” says Bettina Tangman, aWeb master for keithurbanfans.com.“I am proud of the other fan clubs andI am proud to be a fan of Keith’s.”

Patients are the winnersToby Keith’s “warriors” followed

up their opening salvo with a silentauction through the fan club newslet-ter, which raised $2,135. Kay Johnson,who oversees the fan club newsletterfor the club, expressed her respect andadmiration for the country music fanswho have supported the hospital yearafter year and have taken on this addi-tional challenge.

Until the anonymous $10,000donation through Urban’s fan club,both his and Keith’s groups were run-ning neck and neck. But winning theFan Club Challenge is not at the fore-front of everyone’s minds.

“I’m not real worried about win-ning the challenge,” says Johnson.“I’m just worried about raising asmuch money as we possibly can for St. Jude … for the kids.”

“Since we began Country Cares wehave known that country music fanshave a special place in their hearts forSt. Jude,” says David L. McKee,ALSAC’s chief operating officer. “Theresponse to the Fan Club Challengehas again shown the generosity thatthis musical genre and its fans have forour children.”�

Country Cares for St. Jude Kids radiothons havebecome one of the biggest fund-raising programsfor St. Jude Children’s Research Hospital.Through Country Cares, the fans of countrymusic have raised more than $181 million in

pledges in the program’s 14-year history.But country music star Keith Urban thought they could

do much more.

The challengeThe day before the 2002 Fan Fair, an annual gathering

where country music stars mingle and greet with fans,Urban invited members of his and other fan clubs to areception. There he issued what is now known as the “FanClub Challenge.”

BY JOE HANNA

Country music fan clubsare competing to raisemoney for St. Jude kids.

Fan-tastic

CHALLENGE

Oklahoman Caitlyn Garner

benefits fromthe dedication

of countrymusic fans.

Wynonna Juddconnects with

St. Jude patientAnnalisa Burrow,

who is in isolationat the hospital.

Wynonna’s fansare helping raise

funds for St. Jude.

Keith Urban listens intently to St. Jude patient Ishmael Lawrence during a visit to thehospital. Urban has challenged members of country music fan clubs to compete againstone another in a St. Jude fund-raising effort.

LAU

RA

HA

JAR

JER

E PA

RO

BE

K

EVA

NN

E N

EW

MA

N


Like most children growing up in the1950s, television played an importantrole in my life. One of my favorite pro-grams was Make Room For Daddy,starring Danny Thomas. I rememberthe day and time it aired: Mondays at9 p.m.

When I was 7, I built a little radiostation in the basement of our family’shome. Throughout junior and seniorhigh school and college, I was a discjockey at a local radio station. When Iwas 19, I was asked to serve asTeenage March captain for the annual

fund drive for ALSAC, the fund-raisingarm of St. Jude Children‘s ResearchHospital. My boss thought I would be

an excellent choice, since I was the station’s top-rated disc jockey amongthe teen audience. I was honored bythe offer, but I really knew little aboutthe cause.

During the weeks leading up to theevent, I learned how Danny Thomashad promised he would build a shrine

to honor St. Jude. I wastold Elvis had donated ayacht, once owned byPresident Roosevelt, tothe hospital. But mostimportant, I learned thatSt. Jude was dedicated tocuring children strickenwith cancer.

Although I was a hot-shot radio personalitywith a fancy sports carand a “flower power”wardrobe, I worked end-lessly to make that funddrive succeed.Afterward, I attendedthe national conventionin Cincinnati, Ohio.Danny Thomas waspresent.

A photo was taken tomemorialize my meetingwith Mr. Thomas.Talking to the man I hadwatched on TV was

cool. But having him thankme for the efforts I had put forth onbehalf of St. Jude was even better—anexperience I will always remember. In

fact, I recall the exact words he said,even though it was more than 30 years ago.

Throughout my career, I have keptin mind the promise that DannyThomas made to St. Jude. I am not astrongly religious person; however, not a day goes by that I do not pray toSt. Jude. The reason I honor him istwofold. First, he has given mestrength when I was tired and forlorn.But more important, he is watchingover those helpless, beautiful and pre-cious children who find comfort, hopeand love at St. Jude Children’sResearch Hospital. Thank you, St. Jude and the staff at ALSAC, forallowing me to tell my story. I hope itwill inspire others to get involved.

The recipient of two Grammy nomina-tions, Ron Seggi has owned radio stations, an advertising agency and iscurrently CEO and president of a production company at UniversalStudios Florida. He also produces aradio show for his partner, EdMcMahon. In 2003, Seggi will be producing and hosting a weeklynational television show based on thelegends of rock ’n’ roll. In addition,Seggi hosts a nationally syndicatedtalk show, where Marlo Thomas

recently discussed her book, The Right Words at the Right Time. Allproceeds from the sale of that book goto St. Jude.

PerspectiveBroadcasting the mission

By Ron Seggi

Many a little boy has dreamed of being a cowboy, riding the range and sleeping beneath the stars.Edwin Kennedy and some of his friends did just that recently—and they did it so that little boys andgirls could continue to have dreams of their own. Kennedy and five friends hitched up a couple of cov-ered wagons to some mules in Louisiana and rode them north toward Memphis in an effort to raisefunds and awareness for St. Jude. Three weeks later, they pulled up to St. Jude.

For Kennedy, a retired rodeo clown, the trip was an emotional apex. Last August, doctors told him his oldest daughter had a tumor. He prayed that the doctors were wrong. He added a vow, much like St. Jude founder Danny Thomas, that if his little girl would be all right, he would devote himself to St. Jude and the hospital that bears the saint’s name.

Some time later, doctors told the family the original diagnosis was in error and that Kennedy’s oldestdaughter did not have a tumor. Amid the feelings of relief, Kennedy remembered his promise and beganto put together what would be called Cowboys Against Childhood Cancer Tour the United States(CACCTUS).

The donations Kennedy and his group raised have yet to be tallied. But the feeling of accomplishmenthe felt and the smiles he saw of the patients who came out to greet him have reaffirmed his dedicationand his desire to take three weeks again next year and follow his little-boy dream of being a cowboyand doing it to help children fighting cancer.

A nationally syndicated radio personality explains his

passion for the work of St. Jude.

Danny Thomas and Ron Seggi

LAU

RA

HA

JAR

Documents

Promise – Spring 2003