Preparing for the next generation

Preparing for the next generation.

S H Orkin

J Clin Invest.

1990;

86(6)

:1773-1776.

https://doi.org/10.1172/JCI114905

.

Research Article

Find the latest version:

Perspectives

Preparing

for

the Next

Generation

Presidential Address tothe American Society for Clinical Investigation, Washington, DC, 7 May 1990

StuartH.Orkin

Division ofHematology-Oncology, Children's Hospital, Department ofPediatrics, Harvard Medical School, Howard Hughes Medical Institute, Boston, Massachusetts 02115

Members and guests, for the past year it has been my honor and pleasuretoserve asPresident of the American Society of Clinical Investigation, an organization dedicated to the ad-vancement of biomedical and clinical science. The healthof oursociety and thevigorof these annualmeetings reflect

re-cent advancesin theapplicationof science to medicineand, morebroadly,theoverallstateof academic medicine. We have aconsiderable tradition inthissociety. Many eminent physi-ciansandinvestigatorshavepreceededme asPresident,and, I trust, manymorewillfollow.AsPresident oftheASCI,Ihave had theoccasion to reflecton issuesand problemsrelatedto

thepropagationofourspecies.Andsomeof these concernsare

thetopic ofmyaddress thismorning.

Asthose who know myacademic historycanattest, I am

notthetypical individualtohave been chosenasPresident of the ASCI.In contrast tomanyrecentPresidents, Ihavenever

servedasChairman ofaDepartmentof

Medicine,

asChiefofa

ClinicalDivision,or asBranchChiefattheNational Institutes ofHealth. Iknowlittle ofthefinancialstructureofAmerican medicine, nor honestly have spent much time ponderingits problems. Infact, as my clinical experience has beenlargely restricted to pediatrics, I knowprecious little about internal medicine, the primary focus ofmost ofthe membersofthe

society.

Instead,Ihave spent thevast

majority

ofmyacademic

careerdevelopingmypersonalresearchinterestsin thecontext

andenvironment ofaclinical

division, working

withclinical fellowsandbasic science

postdoctoral

fellowswhocome tomy laboratory to pursue common researchgoals,andparticipating in thetraining ofthose whoIexpect will be mysuccessors.So what then canthis atypical ASCI presidentand pediatrician say to this group? My message is deceptively simple, yet a

challengeto usall. Ifbiomedical science andacademic medi-cineare toremain vibrant andhealthy intothenextcentury, wemustconcernourselves more than we have to date with the quality of,andcommitmentto,science educationinour

coun-try,notjustatthecollegeandpostgraduatelevels butfar

ear-lier. At thismoment the report cardis notgood, and future prospectsdependonreversing thistrend.

Biomedical sciencehasexperiencedaprofound revolution

in the past decade, driven largely by advances in molecular biology.RecombinantDNAmethods have become centralnot

only to geneticsper se, but to cell biology, cancer biology,

Receivedforpublication27August1990.

immunology, andneurobiology. Fundamentalproblems in all these areas have been solved or "cracked" in recent years. Manyofthebasicfeatures ofgeneregulationand cell differen-tiationare nowevident.

Specific

genes that

participate

in the initiation and progression of diverse malignancies are now

known. The genetic and structural bases for antigen recogni-tionandcell-cellinteractionsin theimmunesystem are being defined. Furthermore, proteinproducts generated through re-combinant DNA technology are nowmaking theirway into theclinicalarenaasnewpharmaceuticals. Infact,anindustry still in its infancy, that of biotechnology, was born of this revolution.

Those of us pursuing research activities identified with clinical problems have been the beneficiaries ofmany basic discoveriesand technical advances, often developed in what havetraditionally beenregarded as"basic science" or Ph.D.-baseddepartmentsworldwide. Althoughtherecanbeno

accu-rate measure ofthe true impact ofmolecularbiology onthe

courseof clinicalinvestigation, animpressivetrendis evident from inspection ofourplenary sessionsoverthe past decade (Fig. 1). The percentage of delivered papers relating findings basedon molecular

cloning

orthestudy ofcloned genesand theirexpression is plotted for

representative

yearsduring this

period.

Whereas such paperswere

infrequent

in theyearsfrom 1980to 1986, they dominate thereafter. Suchanabrupt

tran-sition necessitates the

acquisition

ofa newvocabularyandnew

research skills.For many in theASCIthis has beenan exhila-ratingchallenge,met withgreatenthusiasm and success. For others, ithas beenacontinuing frustration.Asamajor

propo-nentand architect of thisprogression, though, Icontend that thedye is cast. At present, moleculartechniques are rapidly being assimilated in "nonmolecular laboratories", much the

same aspolyacrylamide gel electrophoresisand theroutineuse of antibodieswerein the

previous

decade. Thevastmajority of you are very familiar with thejargon ofmolecular biology. Indeed, manyofyou have themosttangible evidence ofthese recentdevelopments,a"PCR" machine,in yourlaboratories. Whatthisrevolutionin technology announces loud and clear is that we mustbe prepared for change. We must bepliable enoughtomodifythecourseofourworkwith each new, and

perhapsunanticipated, revolutioninscience. In 1986 Dr. Jo-seph Goldstein describeda newclinical syndrome, "PAIDS"

orparalyzedacademicinvestigator'sdisease (1), which results from the inabilityto adapt in such a dynamic environment. Thedisease is still with us, and is usually fatal. The epidemic continues. Mytreatment ismeant to prevent the first

symp-toms.

Many forces conspire toundermine the goals and aspira-tionsofthe ASCI and its members. Although biomedical

re-search inthis country is unparalleled elsewhere in the world,

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Figure 1. Riseof"molecular"papers presented at ASCI plenary ses-sions

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there

is

thesensethatwe areunder assault.Some inourmidsts

feel

that our

"private"

domain,

human

biology,

is

being

wrestedfromus, as

Ph.D.-trained

molecular

biologists,

immu-nologists,

orcell

biologists

have been drawn into the

study

of humansystemsto a greater extent overthepastseveralyears. As many

fundamental mechanisms

ofgene

regulation

and differentiationare seen tobe conservedfrom

simple organisms

to man, it is no

longer

considered an embarrassment for a

"basic

scientist"

to

investigate

ahumandisorder. Although the

public

appears to have an

insatiable appetite

for

"medical

breakthroughs"

reportedweekly inthe press, we alsohave the

perception

thatbiomedical researchmustbe rather lowonthe

priority

list ofourrepresentatives in government. Evennow, when old

conflicts

between East and West appear tobe

dis-solving

amid democraticandnationalistic

fervor,

we aretold that the

"peace dividend"

for social

concerns,

andIinfer also research,

is

likely

tobe small.Atthis

time,

consequent tothese

forces

and

compounded by administrative

decisions,

grant

funding through

the NIH is themost

competitive

anddifficult in recentmemory. If

funding

paylines

are in the 10-15

per-centile

range,whatmessagedoesthis sendtobiomedical

scien-tists,

present orfuture?

Although

theimmediate

impass

may bealleviated somewhat in thenextfewyears,no oneissobold as to

predict

dramatic

improvements

soonenough. Ifallthis were not

discouraging,

forces

conspire

tounderminemedicine and medical research as a

profession.

Medical economics is now a

major

component

of

medical

practice

as wellas

aca-demic

medicine.

Medicine,

onceidealized in the minds of the

public,

haslost much of its luster and isno

longer

viewedso

highly

bycollege students faced with theprospectofan expen-sive medical education and

(perhaps)

atediouscareer thereaf-ter.Itisnowonder thata careerin

business,

withthe

promise

ofa

quicker

(andmore

substantial) pay-off,

is saidtobemore

attractive.

And,

if thiswere not

enough,

the

integrity

of basic andclinicalresearchers has been

impuned by

thosewhofailto

distinguishbetween

interpretive

differencesencountered regu-larly in scienceandoutright fraud. Instancesof

fraud,

abuse, andconflict of interest in biomedical scienceare indeniable.

Collectively,

all engaged in our

professional

activitiesshould be embarrassed.

Nonetheless,

these instances are rare and shouldnotbeusedtofuelambitions of those

trying

to

regulate

scienceormedicine.

Inappropriate

witch hunts directedat our nation'smostrespected andhonorable scientistsonly serve to undermine thefoundations of biomedical science.

So,

times are difficult. Is it

surprising

that many

depart-mentchairmen wonder whether the next

generation

of

aca-demicresearchers willemerge totake their places? While those inclinicalcircles areworrying about theinfluxof new talent,I can assure youthatchairmen of basic sciencedepartments are concerned,too.Shouldwethrowour hands up in despairand let our careersandthe ASCIjustfadeaway? Ithink not. The excitement and promise in the biomedical sciences are the greatest they have ever been. It is particularly ironicthat atthe moment at which both achievement and promise are the brighest,wedispairof current conditions and future prospects. Numerous solutions have been proposed to address the perceived failure of current training mechanisms to attract sufficient numbers oftalentedindividualstopursue a career in biomedical research. A lengthy educational "pipeline" sup-pliesfuture scientistsand engineers(Fig. 2), proceeding from earlystagesof education through postgraduate training. With time thereis progressive pruning,sothatonly atiny fractionof entering high school students ultimatelypursuecareersinthe sciences. Ofapproximately 4 million entering high school sophomores in 1977, slightly less than 10,000 (orjust over 0.2%) will earn Ph.D. degree in the sciences in 1992. Many stimulitowhich studentsareexposedduring their formative yearsmayeither increaseordecrease the finalpercentage that choosea scientific path. Amongeducators, thereis consider-able debateregardingthe consequencesof interventionat each phaseof the educationalladder. There are those who contend that maximal

yield

is attainable by capturing the minds of studentsattheearliest stages.Others contend thatit ismore costeffectivetodo so atthecollegelevel.

Preparation fora careerin academicmedical research in the 1990s and beyond requiresafirmgroundingand commit-menttoscience thatIbelieve isnoteasily gained inthe later yearsof formal education.In

effect,

thecomplexities of mod-ernresearchinmedicine requiremoreextendedtrainingatthe bench than

previously

thecustom.Mostof theprograms cur-rently inplaceto

foster

thedevelopmentofbiomedical

scien-tists,

inmy

view, focus

dangerously late in thecourseof intel-lectualdevelopment.Examplesofprogramsaimedatthe grad-uate and postgraduate years

include

M.D.-Ph.D. programs,

100%' _4,000,000

HS Sophomores

HS Seniors

interested in science

College Freshman

planning science major

Science B.S.

3,700)

PhDs

YEAR

Figure2.The science"pipeline". Adapted from reference 6.

Physician Scientist and Clinical Investigator Awards. M.D.-Ph.D. programs are best suited to draw the most talented col-legegraduatesintoresearch, often inexchangefor "no debt" medical education. Subspecialtytraining fellowshipshave

tra-ditionally been used as the major mechanism fordeveloping medicalacademicians. Onlymore recentlyhas the NIH Phy-sician ScientistAward program been initiatedtoprovide addi-tional years in basic science training. Otheragencies, notably the Howard Hughes Medical Institute, have also recognized the increasing need for such programs and have initiated mechanisms for graduatestudentandphysicianscientist sup-port. Although these diverseprograms for

graduate

and post-graduateeducationsupport areabsolutelyessential in the

cur-rentenvironment,I amconcerned thattheyareinsufficient in the long-term for the enormous challenges ahead. Without doubt,our most talented fellows inspecialty trainingmatchor

exceed those who have come before both in potential and commitment. But, their numbers are inadequate to

provide

the investigators and teachers for the future. The veneer of academic biomedical science is alltoothin.

The pediatrician within me keeps

saying

that the root of theproblemswe now face is much earlierthanwehave tradi-tionally consideredourconcern. Itisunreasonable tobelieve that amedical studentorclinical fellowwho has spentnearly 20 years in aformal education system thatdeemphasizesand misrepresents the sciences, should be lured into biomedical researchthrougharelatively brief(three-to-five-year) training periodinwhich both the tools of thetrade are to be mastered and evidence ofaccomplishment is expected. Individuals at

thefellowship stageof theircareersfacemany, often conflict-ing, forces,

including

the need to learn a new language and

discipline

of research, the

gymnastics required

tomanage lon-gitudinalclinicalresponsibilities with the demands ofthe labo-ratory, and the urge to"get onwithone's

life",

thatissupport andraise a

family. Entering

a new

discipline,

suchas labora-toryresearch, isnevereasy.Whenonetriestodosowithouta

firm base, commitment, and love of scientific research, it is nearlyimpossible.

Numerous indicators make it abundantly clear that our educationalsystemsinthiscountryare

failing

atthe task. For example, theUCLA

Cooperative

Institutional Research Pro-gram (CIRP) survey ofentering college freshmen, a study begun in 1966 andcontinuing to the present, indicates that freshman interest in fundamental undergraduate science majorshasdropped

dramatically

overthe past23years,

partic-ularly inthe

physical

sciences

(2). Nonetheless,

during

a

period

that manyofusviewasthe"golden"ageof

biological sciences,

interestamong freshmen in

biology

as amajorhas not kept pace. Freshmaninterestin

faculty

andresearch careers overall has waned over the past two decades

(Fig.

3),somuch so as to cause us to ask whether there will be a next

generation

of academicians. Substantial

defection,

or the switching from science to nonsciencemajors during the ensuingfour years, rendersprojections fromthefreshmanyear overly optimistic. In parallel with these trends, the UCLA survey has docu-mented anincreasing interestin business careers, particularly among women(Fig.4).

Nosolace can begainedby contemplating earlier educa-tion.Amonghighschool studentstakingupper level biology, theUnited States ranked 14th among all countries surveyed for achievement,even

though

biologyis the most

popular

high school science course

(3).

Whereas students in

Singapore

and GreatBritain

provided

correct scoresnearly two-thirdsofthe

49

3

Research _

2-Faculty 'a4c."$,.

'66 70 75 80 '84 '88

Figure3.Freshmaninterest infacultyandresearchcareers

(percent-ages offirst-time,full-timefreshmen in allinstitutions). Reproduced

from reference 2.

time,

USstudentswere

right only

alittlemorethanone-third. Statisticalsurveys of this kindcan

easily

bedistortedto sup-portalmostany

position.

However,

noeducators havecome

forwardto

praise

the

accomplishments

ofourstudents in the sciences. This isnot

something

of whichweshould be

proud.

Thedifficultieswefacearerootedevenearlier inour chil-dren's education. Forone,wehavethesense,

perhaps

asother

generations

have hadbeforeus, thatourstudentsandthe pop-ulace overall are not as aware of "basic information" as we

should be.

Take,

for

example,

the

_embarrassing

failure of many students andtheirelderstoknow

simple

geography

and current events.

Educating

students and the

lay

public

about science has

always posed

a formidable

problem.

The heroic teacher of

Tracy

Kidder'sbest

selling

book

Among

Schoolchil-dren

(4)

lamentsthat she feels

inadequate

in

teaching

science

toher

pupils.

Her responseistoavoidthe

subject.

She left science for last. For several other

subjects

she usedtextbooks,

butonlyasoutlines. Shetaughtscience

right

outof the

book;

thiswas

one of those texts that takes

pains

with the obvious and

gives

the

complexshortshrift.Chris didn't know much science and didn't

enjoy

teachingit.. . .Aboutonedayintenshecanceled science

altogether

and announced-to cheers,

Felippe's

the loudest-an informal art

lesson.Sheoftenfeltguiltyaboutscience.

With such not-so-subtlecuesit isnowonder thatstudents

createtheirown

_images

of scientists

long

before

they

confront science or scientists in a

_meaningful

way. In aclassic

study,

Margaret

Mead

surveyed

some

_35,000

high

schoolstudentsin the mid-1950s

regarding

theirviews of scientists

(5).

A

com-posite

viewof scientists is

easily

translated:

scientists

are

_nerds;

but it was also

expressed

(fortunately)

that science is

impor-tant:

30

25

20

10

Women e

5 4

0

'66 '68 70 72 74 '76 78 80 '82 '84 '86 '88

Figure4.Riseininterestinbusinesscareers among women

Thescientist isa manwhowears awhitecoatandworksina

labora-tory. Heis elderlyormiddle agedand wearsglasses . . .He maybe bald.He may wear abeard,may beunshavenandunkempt.He may

be stooped and tired . . He is surrounded byequipment:testtubes,

bunsenburners, flasksandbottles,ajunglegymofblownglasstubes

andweird machineswith dials. . .Hespends hisdaysdoing

experi-ments.. . He experimentswithplants andanimals, cutting them apart,injectingseruminto animals. . .

Scientistswere viewed as eccentric:

Thescientist isabrain. . .He spends his daysindoors.. His work

is uninteresting,dull, monotonous,tedious, timeconsuming . . . He maylive inacoldwaterflat. . .He may bedangerous.. . If hedoes

medicalresearch,hemaybringhomedisease,ormay usehimselfas a

guineapig,ormay evenaccidentally kill someone. . .He isso in-volved with hisworkthat he doesn't know what is goingoninthe world . . . Hehasnootherinterestsandneglectshisbodyfor his mind

. Hehasnosociallife,nootherintellectual interests,nohobbies,or

relaxations.Heboreshiswife.. . .Hebringshome work and also bugs

andcreepythings.He mayforce his childrentobecomescientistsalso. Ascientistshould not marry. No one wants to be such ascientistor tomarryhim.

We must take particular noteof where scientists might live, perhapsa hintto thoseproviding ourfunding. Traditionally science has also been viewed as obscure, as reflected in this drawing byahighschool student(Fig. 5).

With thisasbackgroundmust wewonderwhy itisthatthe public has little knowledgeor understandingofscience? Is it remarkable thatlegislators believethat science and medicine areimportant,butcannot musterthevotes togiveourfunding

ahigherpriorityscore? Whydoesa mediocre baseballplayer earn 10-20 timesmorethanourmostcommitted and produc-tive biomedical scientists? Although lobbyingour representa-tives to redressgrievances may lessen difficulties inthe short run,onlyprogressive improvementinscienceeducationfrom

Figure 5.Ahighschool student's view ofascientist.Reproduced from reference6.

thebottom upwill succeed in reorienting priorities in the

fu-ture.

Educators have discussed and debated how best to educate students and others about science, and thereby turn the tide. Onecommon theme is thatwe muststimulate curiosity and excitement with direct participation. Almost all agree that rather than emphasizing dry facts and new vocabulary, teachersmust striveto openstudents' eyes tothe wonder of science andtotheexcitment of learning and discovery through active participation in simple experiments, tailored appropri-ately forage.Ineffect,asacademic investigatorsweattempt to

do much the same, but at amuch later time in intellectual development. Although deficiencies in science education have been apparentforsometime, their potentialconsequences to

medicine, science, andto ourcountry are nowbeing addressed openly. Hopeful signs are appearing. For example, several

pri-vate foundations, including the Albert P. Sloan Foundation and the Howard Hughes Medical Institute, have supported

programs for the improvement of science education at the

secondary school and college level. Science education in liberal

artsandtraditionally "nonscience" institutions has been a pri-mary focus of new initiatives. National news magazines in

recent weeks have discussed the general problem and high-lighted several extraordinary teachers whose courses have cap-turedtheimagination oftheirstudents. Weshould hope that

theseextraordinary teachers become the ordinary.

Recognition of the national consequences of scientific illit-eracyhasawakened ourpolitical leaders.LastFebruary

Presi-dent Bush and the nation's governors announced a national

educationgoal"thatbytheyear2000,USstudentswillbe first

inthe worldinmathematics and science achievement." There

are few amonguswho believe we will meetthis goalon our current course. Nonetheless, recognition ofthe need for im-proved science education, at the highest level of this country, shouldgive us somesmall comfort. I do nothave the back-groundnortheexperienceinpublic policy and general

educa-tion to present a coherent program for the solutions to this

challenge. What I have come torealize oflate,though, is that oureffortsinacademicmedicine and researchareinextricably linked to these issues of science education. The future of

aca-demic biomedical research does not rest in our handsalone,

but in those ofelementary, high school, and collegeinstructors

whom we shall never meet. If the"pipeline" is tobe replen-ished, itmustbedoneso atthesource.Thank you.

References

I.Goldstein,J. D. 1986. Ontheoriginandprevention ofPAIDS

(ParalyzedAcademicInvestigator'sDiseaseSyndrome.J. Clin. Invest. 78:848-854.

2.GreenK.C. 1989.Aprofile of undergraduatesin thesciences.In

SigmaXiConferenceonUndergraduateEducation inScience,

Mathe-matics,and EngineeringattheWingspread ConferenceCenter,

Ra-cine,WI(23 January 1989).

3. 1990. Science education:fineryandfadsorfundamentalchange?

J. NIH Res. 2:25-26.

4.Kidder,T. 1989. AmongSchoolchildren. Houghton Mifflin Co., Boston,MA.

5.Mead, M., and R. Metraux. 1957.Imageof the scientist among

high-schoolstudents:apilot study.Science(Wash.DC). 126:384-390. 6. 1988.EducatingScientistsandEngineers:Grade SchooltoGrad School. Office ofTechnology Assessment, Congress of the United

States,Washington, DC.