Focus
Too close
for comfort
m
Colleaguesin radiologypraiseZerhouni
for his intellectandoriginality,althoughhis
researchis not widely known outside his
field. Brody, who was developing a new
MRI machinein Palo Alto, California,before comingto Hopkins,was in California
trying to interestpeople in his new MRI
systemwhenhe first met Zerhouni.At that
time,Brodynotes,"peoplewerewritingarticles about how [the system] wouldn't
work."Zerhounicame to evaluate it for
Hopkins,and,accordingto Brody,he concludedthattheideawouldsucceed.
Brody says that Zerhounimay be best
knownfor pioneeringnoninvasivemethods
of analyzingthe movementsof the heartby
electrically"tagging"the musclewall with
superimposedmagneticlines and tracking
themotionswithMRI.Magnetictagginghas
enabledphysiologiststo analyzeand compare living healthyand diseasedheartsin
threedimensions,withoutsurgery.Noninvasive imagingof this sort,says JamesThrall,
chairof radiologyat Massachusetts
General
Hospitalin Boston,hasbecomethe"guiding
handof medicine"in the last decade.Thrall
also creditsZerhounifor helpingsupportradiologists'effortsto gaina strongerpresence
on the NIH campusthroughcreationof the
NationalInstituteof BiomedicalImaging
andBioengineering.
Congressapprovedit in
2000, despiteoppositionfromformerNIH
chiefHaroldVarmus.
Zerhouni'sresumelists him as "consulting"adviserto the WhiteHouseduringthe
z ReaganAdministration,and he currently
serves on the scientific advisoryboardof
| the National CancerInstitute(NCI). Coo panelistHerbertKressel,a radiologistand
o presidentof HarvardUniversity'sBeth Is8 rael DeaconessMedicalCenterin Boston,
8 calls Zerhouni"one of those people who
can see the entireplayingfield and all the
relationshipson it." Zerhouniis "persono able,"Kressel says, but he has never discussedpolitics or mentionedhis views on
embryoresearch.
FormerNCI directorRichardKlausner,
_
o whorecruitedZerhounifor adviceon tumor
Special report:
Hardchoices
in public
health
MIlV
'- %,
I
ful, and knowledgeable"about deploying
the center'sresourcesduringa reviewof its
radiologyprogram,Varmussays: "I hadn't
heardof him 3 yearsago, butI havea lot of
respectforhim."
Despite the praise,Zerhounicould run
into some flak in Senate confirmation hearings. Questioners will be
poised to ask if, as reported, he
passed a political "litmus test" on
stem cell policy that other candidates flunked. For example, one
knowledgeable NIH insider says
news reportsare essentiallycorrect
that anotherleading candidate,AnthonyFauci,directorof the National
Institute of Allergy and Infectious
Diseases, failed to promise to restrictresearchon humanembryonic
stemcells.
The idea of measuring an NIH
nominee's politics is distasteful to
many basic scientists, who worry
that such screening could weaken
p
NIH's stature as the government's
q
biomedical crownjewel. "If someone as thoughtful and careful and
4
balanced as Tony Fauci was unacceptable," says Steven Hyman,
provost of HarvardUniversity and
formermental health chief at NIH, "that
reallydoes raisesome questions."
-ELIOTMARSHALL
Studies Cast Doubt on
Plasticity of Adult Cells
Opponentsof researchon humanembryos
haveraiseda politicallypowerfulargument
against work involving embryonic stem
(ES)cells:Suchresearchcanbe avoidedbecause adult stem cells may offer similar
promise.Defyingscientificdogma,numerous reportshave suggestedthatadultstem
cells can morphinto many types of cells,
raisinghopesthatadultcells couldeventually be used to treat diseases-without the
z imaging, calls him "a clear thinker.... [Zer- ethicalbaggagethataccompanies
ES cells.
"
interestedin technoloNow two papersin this week'searlyonhouni]is particularly
of Naturesuggestthatsome
gy,"Klausneradds,buthe'salso "verysup- line publication
9 portiveof science and the cultureof sci- of thesurprising
plasticityof adultstemcells
ence"despitelackingexperienceas a basic mightbe explainedby simplecell fusion,not
Z bench scientist.Varmus,now presidentof "reprogramming."
The new evidencedoes
CancerCen- not explainawayall of the potentialof adult
o the MemorialSloan-Kettering
a ter in New YorkCity,is also upbeatabout stemcells,butit doesraisea caution.
s Zerhouni'stalents.He was "smart,insightForyears,researchers
haveassumedthat
.
.J
www.sciencemag.org SCIENCE VOL295
developmentis a one-waystreet:A cell that
startsdownthepathto becomea neuron,for
instance,can becomeonly a braincell. But
studiesin the pastfew yearshavesuggested
that cells might indeed be coaxed to turn
backandtakeanotherpath.Nearlya dozen
teamshavereported
that cells from one
tissue-blood, muscle, or brain, for
example-could,
whenexposedto the
right environment,
contributeto an entirelydifferenttissue
(Science, 8 June
2001,p. 1820).
Althoughpoliticians have trumpeted the results,many
developmentalbiologists have been
skeptical.Inthenew
papers,two groups,
working independently,provideevidence for one alternative explanation.
Both report that
cells fromadulttisMore than enough.
Cellsthat appearto sues can fuse with
have been "repro- ES cells in culture,
a
grammed" have en- producing hybrid
that
like
looks
a relarged nuclei (top)
and twice the normal programmedadult
number of chromo- cell but has the
somes (bottom), sug- pluripotentcharacgesting that two cells teristics of the emfusedtogether.
bryonic cell. The
hybrid cells also
show chromosomalabnormalities,
suggest.ing thatthey mightnot be a reliablesource
of healthyreplacement
tissueafterall.
Cell biologistNaohiroTeradaof the University of FloridaCollege of Medicinein
Gainesvilleandhis colleagueswereeagerto
coaxadultcellsto "dedifferentiate"
intocells
with unlimitedpotential.Otherwork had
suggestedthatsome factorproducedby ES
cells mightkick-start
theprocess.Totestthat
idea,Terada,EdwardScott, and othercolleagues culturedadult cells from mouse
bone marrowtaggedwith greenfluorescent
proteintogetherwith ES cells thatdid not
carry the marker.The researchers soon
foundevidencefor greencells thatbehaved
like ES cells. But when they lookedmore
closely,theyfoundthatall the "dedifferenti-
15 MARCH2002
1989
NEWS
ated"cells hadtwice as manychromosomes
as usual:Theyweretheproductof fusionbetweentwo cells.Teradadoesn'tthinkthatfuresionexplainsall theotherreprogramming
sults."We'renot denyingany of thosedata.
We'rejust saying,'Be careful'" aboutpossibleexplanations
forunexpected
results.
DevelopmentalgeneticistAustin Smith
of the Universityof Edinburgh,U.K., says
he andthe team"approached
the issue with
"All
minds."
our other
but
open
skeptical
datasaidcells do becomelineagerestricted"
-unable to form new kindsof tissues-as
theyprogresstowardbecominga certaincell
type.He andhis colleaguesgrewcells from
adult mouse brains in a culturethat also
containedmouseES cells.Theythenselected for cells thatexpressedOct4 (a protein
ES cells)
characteristicof undifferentiated
and also carrieda gene presentonly in the
braincells. The team recoveredmore than
two dozencell coloniesthatseemedto have
But on closer inspecbeen reprogrammed.
tion,the cells hadenlargednucleiandtwice
as manychromosomesas normal:signs of
ones.
hybridcells,notreprogrammed
arenot
Severalof the originalresearchers
dissuaded."Whatthey'resayingis, 'Hey,fusion happens,'" says DianeKrauseof Yale
who has reportedthatcells from
University,
bonemarrowcanbecomea varietyof tissues
wheninjectedintoadultmice.Herlabis now
checking whether its apparently reprogrammedcells formedfromfusionof donor
and recipientcells. JonasFrisen,whose lab
thatbraincellscanbecomea variety
reported
of tissueswheninjectedintoembryos,is also
checkingfor evidenceof hybridcells,buthe
does not believethatcell fusioncan explain
all of theirresults.
Thenewpaperscomeon theheelsof two
othersthathavecast doubton the reported
malleabilityof adultcells. In the Marchissue of Nature Medicine, Derek van Der
Kooy,CindiMorshead,andtheircolleagues
at the Universityof Torontoreportthatthey
couldnotreplicateearlierreportsthat
cells fromadultbraincould become
blood cells (Science, 22 January
1999,pp. 471 and534). Instead,they
report,cells keptin culturefor many
generations-asoccurredin the originalresearch-tendto accumulate
geneticalterationsthatmightleadto an
apparent
reprogramming.
And in February, Margaret
Goodell of Baylor College of
Medicine in Houstonclarified one
| of her earlierreportson cells from
adult mouse muscle. As she ex| plained in the Proceedings of the
z National
Academyof Sciences, the
" adultcells that seemed to give rise
| to blood cells were in fact rareblood stem
cells thatresidein the muscle.
OF
THE
WEEK
The new resultsare a neededreminder
for the field to stay vigilant,says van Der
Kooy."Ourown datafail to replicatetransdifferentiation,but there are so many reports out there. I'm still unwilling to believe all of themarefalse."
-GRETCHEN
VOGEL
South KoreaScrambles
To FillPh.D.Slots
SEOUL-Jae-GwangWon is a member of an
increasinglyrarebreed:a Koreangraduate
studentworkingon a homegrownscience
Ph.D.This monthSeoulNationalUniversity
(SNU), long consideredthe country'smost
prestigiousuniversity,failedto fill its quota
of graduateslotsforthe new semester.More
embarrassingstill, SNU wouldhave fallen
shortevenif it hadacceptedeveryapplicant.
Korea'spostwareconomicboom in the
1960s and 1970s certainlybenefitedfrom
the belief thattechnicalknow-howwas essential for a rising standardof living. Althoughmanyof thosescientistsweretrained
abroad,the strategypaid off: By 1995, for
example, Korea'seconomy was the 11th
largest in the world,and the countrywas
second behindthe United Kingdomin the
percentageof its college-age population
with technicaldegrees."Itwas a good time
for science in Korea,"says Sung H. Park,
SNU's dean of naturalsciences, and there
wereplentyof goodjobs.
Faith in technology as an economic
driverhasn'tdisappeared,
but it's being underminedby severalfactors.One is a loss
in status."WhenI was in high school, science was prestigious," says 53-year-old
YoonSoon-chang,an SNU professorof atmosphericscience and associate dean of
planning."Being a scientist meant being
proud."But today'sstudentsare more interestedin careersthatpaywell,Yoonsays.
Won,seated,with
Minorityview.Jae-Gwang
is partof a dwinSNUdeanYoonSoon-chang,
dlingpoolof gradstudents.
ScienceScepe
SouthernLightSpainisjoiningthe synclub.The
scienceministrylast
chrotron
weekapproved
firstmajor
building
Spain's
three-dimensional
strucfacilityforprobing
tures.Planscallforbreaking
groundnext
2.5-gigaelectron
yearonthe $110million,
voltradiation
sourceto openin2008near
of Barcelona
theAutonomous
University
newcenter-proposedbya
(UAB).The
UAB-led
teamin 1997-will haveroomfor
teams,planners
say.And
upto 160research
it willbe opento scientistsfromacross
notesAndreuMas-Colell,
souther Europe,
research
headof the Catalan
government's
whichwillsplitthe project's
department,
costwiththe nationalgoverment.
whousesmall
ProteinProbesBiologists
moleculesto explorehowproteinsworkanapproach
knownas"chemical
genetics"
-will soonhavea majornewresource.The
NationalCancerInstitutehasjustawarded
a $40 million,5-yearcontractto Harvard
fora Molecular
TargetLaboratoUniversity
to be headedbyStuart
ry.Thefacility,
of Harvard's
willbeanoutgrowth
Schreiber,
andCell
4-year-oldInstituteof Chemistry
Itwilldeveloptoolssuchas protein
Biology.
arraysandbuilda publicdatabasethatwill
catalogupto a millionsmaltmoleculesandotherlabsbyHarvard
synthesized
thatblockorinteractwithproteins.
Thehighcostof the robotics,
proteinassays,andothertoolsneededto systematicallyscreensets of molecular
probeshas
chemicalgeneticsfromtaking
prevented
of the
off,noteschemistBrentStockwell
MasInstituteinCambridge,
Whitehead
sachusetts:
"lt'snotaneasymethodto imthiswillmakeit moreaccessible."
plement;
Wardsaysit'snotyet
Harvard's
Rebecca
knownwhenthe datawillgo online.
Gettingto BasicsTheU.S.government
shouldfundonlybasicresearchthat is of
highquality,is relevantto government
missions,andmeetsclearperformance
to draftguidelinesregoals,according
leasedearlierthismonthbytheWhite
andBudget
HouseOfficeof Management
(OMB)(seewww7.nationalacademies.org/
no researcher
arguedwith
gpra).Although
that holytrinityat a recentNational
Academyof Sciencesworkshopon the criteria,manywonderedaboutexactlyhow
theywillbe usedto decidewhichprogramsdeservecash-particularlywhenit
researchthat is bound
comesto high-risk
to stumble.Maybe,OMB'sSarahHorrigan
suggested,the guidelinesshouldinclude
"awayto rewardscientificfailure."That
andotherchangescouldbe includedin
OMB'snextdraft,dueout laterthisyear.
2002
www.sciencemag.orgSCIENCEVOL295 15 MARCH
1991