National Institute of Allergy and Infectious Diseases, NIH: Volume 2;Impact on Global Health

769 Pages·2009·12.53 MB·English

by  Vassil St. Georgiev PhD (auth.)

National Institute of Allergy and Infectious
Diseases, NIH
Volume 2
Impact on Global Health
Infectious Disease
VassilSt. Georgiev
Forfurthervolumes,goto
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National Institute of Allergy
and Infectious Diseases, NIH
Volume 2
Impact on Global Health
VassilSt.Georgiev,PhD
Office of Global Research, National Institute of Allergy
and Infectious Diseases, NIH, Bethesda, MD, USA
Forewordby AnthonyS.Fauci,MD
Director, National Institute of Allergy and Infectious Diseases,
NIH, Bethesda, MD, USA
VassilSt.Georgiev,Ph.D.
NationalInstitutesofHealth
DepartmentofHealthandHumanServices
6610RockledgeDrive
BethesdaMD20892
USA
[email protected]
ISBN978-1-60327-296-4 e-ISBN978-1-60327-297-1
DOI10.1007/978-1-60327-297-1
LibraryofCongressControlNumber:2009920698
(cid:2)c HumanaPress,apartofSpringerScience+BusinessMedia,LLC2009
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Dedication
To theNationalInstituteofAllergyandInfectiousDiseases,NIH,
a worldleader insupportingbiomedicalresearch in servicetohumanity
formorethan50 years.
Foreword
TheNIHspeakstheuniversallanguageofhumanitarianism...[it]has
recognizednolimitationsimposedbyinternationalboundaries;has
recognizednodistinctionsofrace,orcreed,orofcolor.
—U.S.PresidentFranklinD.Roosevelt,NationalInstituteofHealth,
Bethesda,Maryland,31October1940
IndedicatingtheNIHcampusin1940,PresidentRooseveltcouldlookbacktoaproudsci-
entificerathatbeganaroundthetimeofhisbirthin1882.InthosedaysofKochandPasteur,the
causesofimportantinfectiousdiseases,suchascholera,tuberculosis,anddiphtheria,weredis-
covered,andmanyvaccinesandtherapeuticswererapidlydeveloped.ItwascleartoRoosevelt
andtoscientistsofhistimethatinfectiousdiseaseswereanimportantglobalproblem.Manyof
themostsignificantinfectiousdiseasediscoveriesofthelate19thandearly20thcenturieshad
come from Africa, the Middle East, South America, and elsewhere in the developingworld.
For example,the discoveryof the cause of yellowfeverand the first successes in its control
came frompartnershipsbetween American and foreignscientists workingin Cuba, Panama,
andotherlocales.
Roosevelt’s inspiring words on that autumn day on the NIH campus indicate that he was
looking not just to the past, but boldly ahead to the future as well. Viewing the future with
optimism, rather than trepidation, he expected significant new challenges and imagined that
NIH would do whatever necessary to meet them. Nearly seven decades later, the world’s
populationhasgrowntomorethan6 billionpeople,from2.3billionin Roosevelt’sday,and
the world is significantly more complicated. Hundreds of new diseases have emerged, and
theyhavecreatedanenormousburdenonhumankind.AIDS,emerginginfluenzastrains,and
drug-resistantmalariaandtuberculosishavecollectivelykilledhundredsofmillionsofpeople.
Immunologic and immunodeficiencydiseases have assumed a much greater role in creating
humanmisery,whilesuchneglectedtropicaldiseasesasschistosomiasiscontinuetoexactan
immense toll on morbidity,mortality and the economiesof developingnations. At the same
time,humanmovementhasincreasedandbecomemoreefficient,transportingmicroorganisms
fromcontinenttocontinentwithinhours.Technologicaladvances,suchasvaccinesanddrugs,
have been counteredby the rapid emergenceof microbialresistance. Biological warfare has
beenrebornfromitsmilitarygraveyardasacivilianthreat.Andthegapbetweenrichandpoor
haswidened,leadingto healthdisparitiesso glaringthatonemightdividethe worldintothe
healthyandthe unhealthy.Thechallengefor the NationalInstitute of AllergyandInfectious
Diseases(NIAID),nowthesecondlargestNIHinstitute,istorespondtothefoundingvision
ofPresidentRooseveltandto thehopesandexpectationsofthose scientistsandleaderswho
camebeforeus.
We hope that this detailed summary of NIAID’s global research efforts will be useful to
bothscientistsandhistoriansofscienceandalsoremindusofthespiritandoptimismthatled
tothecreationofNIH,includingNIAIDanditsforebears.Whileexaminingthemanyspecific
detailsdescribingtheapproaches,initiatives,programs,andscientificactivitiesrelatedtoour
globalresearchmission,wealsorememberthelargerworldwithinwhichwework.Wewish
vii
viii Foreword
to make severalpoints that address not only what we do scientifically, but how and why we
doit.
We are global citizens, and our world view remains humanitarian. President Roosevelt’s
dedicationofNIHmanyyearsagoreflectednotonlyanunderstandingofAmericansciencebut
alsoanationalcommitmenttoglobalcitizenship.Forsevendecades,thisglobalcommitment
has been manifested in NIH’s globalscientific efforts,includingthose of NIAID. For exam-
ple, NIAID playeda leadingrole in finding the causes of, and understandingthe pathogenic
mechanisms of AIDS and in developing, testing, and bringing into use an armamentarium
of drugs that have improved and prolonged the lives of millions of patients. Because these
remarkable achievements were most urgently needed in the developing world, NIAID drew
upon the international AIDS research infrastructure it had created and fostered, partnering
with other governmentsand philanthropicorganizationsto begin the slow process of saving
livesandpreventingnewinfectionsineveryregionoftheworld.Theseeffortswereintegralto
ThePresident’sEmergencyPlanforAIDSRelief(PEPFAR),alarge-scalehumanitariancom-
mitmenttodevelopingnationstopreventandtreatHIV/AIDSandtocareforinfectedpeople.
Althoughmuch remains to be done in the fight againstAIDS, PEPFAR has been a triumph.
The programis an affirmationof traditionalAmerican valuesand a strong confirmationthat
scientificaccomplishmentcanalsobeahumanitarianinstrument.
In a global village, it is no longer possible to geographicallycompartmentalize biomedi-
cal research. The spread of West Nile virus into the Western Hemisphere in 1999;the 2003
AmericanoutbreakoftheimportedAfricandiseasemonkeypox;andwidelypublicizedcases
of multidrug-resistant tuberculosis remind us that the “our disease/their disease” paradigm
is untenable. Most infectious disease threats Americans have faced in the past few decades,
from exotic tropical diseases to antibiotic-resistant strains of bacteria to emerging strains of
influenzaviruses,havecomewhollyorpartiallyfromabroad.Obviously,tounderstandthese
diseasesand the threatstheypose, we mustbeable to studythe causativeorganismsin their
naturalenvironmentsandtoworkcollaborativelywithforeignscientistswhohavethecapacity
toisolatemicrobialstrainsandconductstudiesintheirownendemicareas.Inthepastdecade,
NIHhasembarkeduponanunprecedentedglobalizationofitsresearchbyfocusingonspecific
diseases, such as AIDS, tuberculosis, and malaria, by more than quadrupling direct foreign
research awards and foreign components of domestic awards, by doubling the foreign visi-
tor program,and by joiningforceswith manydevelopingnationsto create a numberof new
andinnovativeresearchpartnerships,suchasNIAID’sInternationalCentersforExcellencein
Research(ICER)andtheIndo-U.S.HIV/STDProgram,amongmanyothers.
The roles of microbial agents and of human hosts in disease occurrence are inextricably
intertwined. The sequencing of the human genome and that of a large number of microbial
pathogensand disease vectorsis leadingus to a much better understandingof howand why
diseasesoccurandwhatcanbedonetocontrolthem.Humansthemselvesandtheirbehaviors,
actions, movements, commerce, and environmentalperturbationsare the selection pressures
thatdrivepathogenemergenceandevolution.Genomicsandproteomicsoffernewopportuni-
tiesnotonlyforpathogendiscovery,diagnostics,anddrug/vaccinedevelopment,butalsofor
understandingmicrobialemergenceandhost-switchingatthegenomelevel.Studyingthehost
response to microbes is critical for a number of reasons: Understanding the genetics of the
immuneresponsetoinfectionsallowsmorerationaldesignofdrugsandvaccinesandprovides
clues to therapy with existing drugs. Host responses may themselves be overexuberantand
even pathogenic, and we need to better understand these immunopathogenic phenomena in
ordertopreventandtreatthem.Moreover,abetterunderstandingofthegeneticvariationsin
hosttargetsmayallowustopredictandevenpreventdiseaseemergence.
Complexproblemsrequirecomplexapproachesandcreativepartnerships;newchallenges
can be met by taking advantage of new opportunities. Many major human infectious dis-
eases are complex and difficult to prevent and control with traditionally successful scien-
tific approaches. For example, each of the three major infectious disease killers worldwide,
HIV, Plasmodium falciparum malaria, and Mycobacterium tuberculosis, all have complex
Foreword ix
“life cycles,” all cause chronic and persistent or recurrent disease, and none has been con-
trolled bya successfulvaccine.The greatburdenof mortalityfromthese threediseases falls
disproportionately on the poor, who live in resource-poor countries. What little money is
availabletoaddresssuchoverwhelmingproblemslocallyisspentintreatmentandprevention,
whilemanydrugandvaccinemanufacturersinwealthynationsremainunmotivatedtoinvest
multimillion-dollareffortstoproducevaccinesanddrugsthatfewcanaffordtobuy.Ittherefore
makessenseforbiomedicalresearch,publichealth,publicpolicy,andphilanthropytoengage
eachotherinnewandcreativeways.AlthoughNIHisthepreeminentfunderofglobalinfec-
tious disease and immunology research, important philanthropic organizations, such as the
Bill &MelindaGatesFoundation,andmanysmallandlargenongovernmentalorganizations
(NGOs)haverecentlyappearedandexpanded.Thesedevelopmentsprovidenewopportunities
toaddressmedical,social,andhumanitarianaspectsofhumanhealth,andtheybringscience
closer to the frontlines ofthe war againstinfectiousdiseases. Increasingly,NIAIDhas been
working collaboratively with foreign governments and scientists, NGOs, and philanthropic
organizations to coordinate comprehensive approaches to important health problems in the
developingworld.Astheworld“shrinks”duetoincreasedtravelandmoreefficientcommu-
nication, and as concentrationsof wealth are brought about by the emerging and realigning
economiesof nationssuch as China and India,new opportunitiesfor scientific progresswill
undoubtedlycontinue to appear. We must remain flexible and retain a capacity to form new
allianceswithavarietyofpartnersinpursuitofever-changingdiseasethreats.
The biomedical science pathway begins with basic research findings and ends with their
translationintolife-savingtoolsandapproaches.AsPasteurfamouslyobserved,“theredoes
not exist a category of science to which one can give the name applied science. There are
scienceandtheapplicationsofscience,boundtogetherasthefruitofthetreewhichbearsit.”
In recent decades, biomedical science has been driven by technological advances, but basic
science discovery itself is only the beginning of a process. An example of the successful
progressofscientificendeavorinaddressinganimportantproblem,notedabove,isthesequen-
tial clinical-epidemiologic recognition of AIDS, followed by the discovery of the etiologic
agent,HIV,followedbythedevelopmentofascreeningdiagnostictest,followedbyscientific
characterizationofthevirus,thedevelopmentofantiviraldrugs,thedevelopmentoftreatment
strategies, and ultimately to the organization of large-scale programs based on accumulated
scientific knowledgeandeffectivedrugsto preventand treatHIVinfections.The “products”
ofscienceincludenotonlythediagnostictests,vaccines,drugs,andpreventionstrategieswe
havedeveloped,butalsotheknowledgeandexperiencewehaveacquiredtousethemwisely.
NIAID’seffortsarepartofalargerprocessthatextendsbeyondthepurelyscientifictoinclude
themedical,societal,andhumanitarian.Scienceisnotavaluesystembutarationalmechanism
fordiscoveringtruths;itacquiresmeaningandvaluewhenweuseittoservehumanity.
For the 54 years of our existence, NIAID has carried on the tradition of NIH and its
antecedentorganizationsinmaintainingaglobalandhumanitarianperspectiveandinviewing
andsupportingbiomedicalscienceasaninstrumentofhumanprogress.Inrecentdecades,we
havemadeenormousstridesineradicatingandcontrollingdiseases,butwehavealsosuffered
discouragingsetbacksintheemergenceofnewdiseasesandthere-emergenceofoldones.We
are in an era in which enormouschallenges,both old and new,are likely to confrontus, but
alsoanerainwhichwewillfindnewopportunitiestomeetthesechallenges.Asdocumentedin
thepagesofthisvolume,ourapproachtothechallengesofinfectiousdiseasesremainsbroad,
flexible, and energetic. We deal with highly complexand technical issues at the level of the
cell,thegene,andthemolecule.Butweseekalsotounderstandthewaysinwhichinfectious
organismsinteractwith,andevolveinresponseto,theirhumanhosts;andwecoordinateour
researchfindingswithcolleaguesinpublichealthandwithpartnersinsocietyatlarge.Indoing
so,weremainfocusedonalleviatinghumansufferingwhereveritoccursandcommittedtoour
foundingprinciples,articulatedintheuniversallanguageofhumanitarianism.
Bethesda,Maryland AnthonyS.Fauci,M.D.
Acknowledgments
DeepappreciationandgratitudeisexpressedtothefollowingcolleaguesfromNIAIDfortheir
helpandencouragementduringthepreparationofthisvolume:
Anthony S. Fauci, MD, Director, National Institute of Allergy and Infectious Diseases
(NIAID),NIH
HughAuchincloss,Jr.,MD,PrincipalDeputyDirector,NIAID,NIH
JohnJ.McGowan,PhD,DeputyDirector,NIAID,NIH
F.GrayHandley,MSPH,AssociateDirectorforInternationalResearchAffairs,NIAID,NIH,
andStevenSmith,JD,Director,OfficeofGlobalResearch,NIAID,NIH,fortheirunderstand-
ingandconstantsupportduringthepreparationofthisvolume;
Division of Microbiology and Infectious Diseases (DMID), NIAID, NIH: Carole Heilman,
PhD,Director,forhercommentsandsupportofPartIofthisvolume;
DivisionofAIDS(DAIDS),NIAID,NIH:CarlDieffenbach,PhD,Director,andJeffNadler,
PhD,JoanRomaine,MPH,VanessaElharrar,MD,FulviaVeronese,PhD,CarlaPettinelli,MD,
andMarjorieDehlinger,DNSc,fortheircommentsandsupportofPartIIofthisvolume;
DivisionofAllergy,Immunology,andTransplantation(DAIT),NIAID,NIH:DanielRotrosen,
MD,Director,andCharlesHackett,PhD,DeputyDirector,fortheircommentsandsupportof
PartIIIofthisvolume;
OfficeofCommunicationsandGovernmentRelations(OCGR),NIAID,NIH:Dr.VedaChar-
rowforeditingofPartsIandIIofthisvolume;
OfficeofCyberInfrastructureandComputationalBiology,CustomerServiceBranch:JamesT.
Mitchellforhistimelyhelpinsolvingcomputerissues.
xi