Does Scientific Progress Come from Projects or People?
Joshua Lederbrrg, The Rockcfcllcr University, NC? York, NY
When t3ob Chlitls callctl inc ;houl spwk-
~ng today, I of course' rccallctl our good
times together at the University of Wiscon-
sin over 30 years ago. I wondcrcd, having
worked cxclu5ivcly al privarc (a cuphcmism
for fcdcral) rchcarch instilutions, namely,
Stuilhrd and The Rockcfcllc1-, all that lime,
h(nv pertincn~ my cxpcriencc would hc Ii11
you. Of course, wc both agreed: all the more
reason for discourse, and in any even1 there
is much more lhal joins private and slalc in-
slilulions in carrying out lllcir rcscarch func-
tions than divides them.
Institutions, how they arc taken for
grant4 and how they scrvc as homes for in-
tellect, will bc the focus of my discussion.
Bob and I and all of us have hccn giving a
lot of thought 10 their status today. My own
experience, and cspccially my prcsenl role,
does constrain me to speak most about the
research mission-and the academic career
of research in the natural sciences.
1 won't be saying very much about overall
budget priorilics-how nJuch WC should co-
lcct in taxes; how 1nuch WC should spend for
defense, for health, for education. `J'hcse
qucslions are easy only for the one who
doesn't have to make IIIC final decisions
about all ofthcse responsibilities of govcrn-
mcnl. So J shoultl not comment on ~hcm
without giving the same u(tcntion to the di-
lemmas of each sector as I will lo my main
topic.
Should we bc complaining? In ter1ns rcl-
ativc to other countries, or much ofour past
history, we have a robust scicntilic cntcr-
prise. Yet 1 believe that, with availnblc
funds, we could be far more cffectivc and
could get better perspectives on J'undarllen-
tal priority allocations. And lroublc is loom-
ing in industrial compctilivcness and in the
morale of younger scientisls as they face lllc
problematical attractions of Ihe scicntilic ca-
reer. The morale of presidents is of less
-
jroad public concern: Steve Mullcr asks,
Where arc the giants of yesteryear? J para-
phrase his answer: They arc collecting rc-
Iurn-deposit beer cans to help pay the bills.
My subject does not knd itsclfto lhc sci-
:ntific process of analysis and vcrificalion
with which I ;IIIJ inost familiar. 1 will call
!JlOrC ancctlola(ly on 35 years aI lhe IilbO~:l-
lory bench and another dccadc in academic
ltlminislr~1lion for an avowedly subjcctivc
.tppraisaI of how f&ml agency funding, our
institutions, and lhe careers of individual sci-
Asts in(cract in that heally twcnticth-ccn-
:ury environment for rescnrch. The institu-
lions' perspectives will also bc noted and
;~I.50 lhc intcri1ction of Ihcsc with the inccn-
lives and opportunities for unconventional
;md incerdiscipiinnry initialivcs. The skclc-
Ion of my remarks co1ncs from a working
paper J submitted during my mcmbcrship on
~IJC Packard-Bromley White House Science
Council panel on the Health of the Univcr-
sities. Despite notable deficiencies in (hat rc-
port-it failed to include my paper verba-
tim--J commend il to you as a high point
of cxiJl~~in;~tion ;iiJd niuhral unders(anding of
the basic issues of the fcdcral-univcrsily rc-
I&nship Coday. Predictably, and just 3s WC
fcarcd, it is being implemented in a quite
sclcctivc and lopsided fashion: ~~:~n~cly,
+,hatcvcr will save lhc fcdcral bud@ short-
rim dollars. I1 does give ;I particularly good
account of our problems in compensating for
long dcfcrred lJl;linkxl~ncc and renewal of
capilal facili(ics and ins(rurncn(ation, SO J
will c01JJr1icnl mainly on the issues of opcr-
sling support for rcscarch J)rograms at aca-
demic instiluthls.
Ar the present tinlc, fcdcral funding ac-
cotmls for ;I lion's share of lhc support 01
  01989 by ISlO CUflnENT CONTENTS@
scientific rcscarch at "privalc" universities
alld increasingly at state insti(ulions as well.
From the pcrspcctive of the individual in-
vcstigntor, the dependency on federal funds
is even grcatcr, since the nonfederal input
will be concentrated on faculty salaries and
lhc institulional infrastructure [which is only
partly paid for by indirect cost rccovcry].
For most investigators at universities, very
lilnited funds for the actual conduct of rc-
search are available except from fcdcml
sources. Even a momentary interruption of
support (while it may not immediately im-
pact the investigator's (cnurc as a pro&or)
poses grave stresses on the continuity of the
research, on the employment of lechnical
staff, and on the capacity and opportunity
of the investigator to continue a research
career.
Since World War II, the scope of federal
support for science has constructively ex-
panded that enterprise to the degree that
complaints about the dccails of research ad-
ministration, and their qualitative impact,
arc in some ways ungracious. So long as the
dependency on federal funds was less than
total, private resources could make up for
discrepancies that arc difficult to rectify in
a government bureaucracy responsive (0 the
politics of both the executive and legislalivc
branches. It is not a good answer to reduce
the scope of our science and technology
when WC have not cxhaustcd the pc>ssibilitics
of constructive reform in the fcdcral-univcr-
sity relationship.
In rcccnt years the ovcrnll financial
slrcsscs on inslitutions, coupled with stern
policies of fcdcral agencies that limit the in-
stitutions' llexibility and draw down their
small uncommiitcd reserves, have left littlc
buffering capacity on the instilutions' part
lo rcinsurc against contingencies.
The predictable conscqucncc is :I confu-
sion of responsibility for the career interest
of the scicntis[: lllC fcdcral ~OVCrIJIJJCJJt h&S
the means for linancial llcxibility but cb-
chews the responsibility; convcrscly, the in-
stitution has the responsibility but not the
means. The loyalties of the scicnlist are Jikc-
wise divided and confused. Only the most
:Iccomplishcd and forhmatc can look beyond
.hc imperative of qualifying for renewal of
heir research gr3lJl. Then pushed aside arc
III other activities, including intcllcctual co-
operation in education as well as research,
.isk taking in the planning of research. cvcn
.eaching out for technology transfer in ap-
Ilying new science. New structural ap-
jroaches to encouraging interdisciplinary
ventures are being actively pressed, cspc-   .
:ially by the National Science Foundation
NSF); but that top-down approach may
:ven compound Ihc problem if it does not
ook closely at the dynamics of the careers
of the creative individuals who arc the real
vcllspring of scirncc and technology pro-
luctivity: their functioning before and after,
s well as during, their participation in thcsc
ICW structures. In my view the best way IO
aster interdisciplinary creativity is not to
mposc new structures, but to liberate indi-
,idual scientists to reconstellatc themselves
s called for by the scientific opportunity.
As this is becoming a controversial policy
ebate, J must display my credentials: my
xperience in interdisciplinary and applica-
ons-oriented work embraces not only mo-
:cular biology, but also applied biotechnol-
gy, world health, computer science, space
xploration, and international relations.)
:ven existing academic structures have be-
ome necessary evils, in some respects.
CURfIENT CONTENTS@  01989 by ISI@   -+% Lj8                    5

from the perspective of encouraging novel
individual initiatives. They will be aggra-
vated by the cluttering of the organization-
;d landscape with still more crosscutting ri-
gidificd "improvcmcnIs" that Ihen take on
a life of their own.
Further compounding these constraints
has been the trend in grants adminis(ration,
during the past decade, ever more to the
project raIher than the investigator as the
locus of merit. Short terms of grant awards
have enhanced the opportunity and inccn-
tivc for micromanagement of others' re-
search, even on Ihc part of peer scicntisls.
This sets up another vicious cycle, Ihat the
burden of grants review constricts the pace
and volume of feedback between the inves-
tigator and the rcvicw process. II is not un-
usual for an applicalion for 3 Iwo-year graIlI
IO require a year's lead time, and thcn-
with very short notice-difficulties crop up
in the prospects of rcncwal that would then
imperil Ihc continuity of Ihe work.
There is great value in peer review-e.g.,
Ihc gatckeeping of the refereed journnls-
which provides indispensable objective crit-
icism and public exposure of new findings
and ideas. AI prcsenI, however, invcstiga-
Iors arc typically spending 20-30 percent 01
their time and cncrgy in suslaining the flow
of grant support and in a selling of high anx-
iety that can only interfere with their cre-
ative thinking. (Yes, there is some optimal
level of accountability and arousal, but no
one can justify what is experienced today.)
Widely misundcrslood, however, it is not
Ihc peer-review but Ihe projccl system IhaI
is the root of this stress, although iI is "peer
review" Ihal has attracted vocal criIicism.
Who better than other working scienlists
could maintain critical oversight on the qual-
ity of science? Of course, one's colleagues
are also one's competitors, and during times
of stringency one needs IO take special pre-
caurions against interested bias and devices
to insist on the accurate reflection of judg-
ments pooled from individual ballots. I have
found that demanding a rank-ordering 01
judgments helps on both counIs: 10 reduce
the negative impact of one idiosyncratic
vole, which gives undue weight to a single
blackball when a11 the absolute votes arc
simply averaged, and to force the judges to
express difficult choices, closer to the con-
sequences of their voles. In the end, after
all, the proposals will hvc to be rank-or-
dered in sOme way to reach a decision on
which will be funded.
Needless to say, the judges should be true
peers, scientists of experience and accom-
plishment-a goal hard to achieve when all
have been so exhausted by their prior scr-
vice: more about that Inter.
It is the short-term emphasis on projects
LhaI amplifies the slrcsscs on individual ca-
rccrs. This is then matched by the systemic
waste that flows from intermiltcnl encour-
nge~wr~t and distress, the nurturing of ca-
reers that are allowed IO sprout, followed
by intervals of droughl or decapitation. The
project system leaves a11 too littlc latiludc
for intrainstilutional measures of criticism
and support. In a word, CilreCrS arc being
administcrcd, de LICIO, by a disIant burcauc-
racy that accepts liltlc rcsponsibilily for this
filCC( of the scientific cnterprisc, while thC
syslem leaves few resources lo local com-
munities of scholars to guide the evolution
of their scholarship or the reeducation of
Ihcir (possibly temporary) weakest links. Al-
togcthcr, the projccl system is in violent con-
tr;idiction wilh Ihc professorial sysfem at the
university. WC would not cast on the dust-
heap a brilliant teacher who had one bad
year. IJut lhis is precisely the prospect fac-
ing the rcscarch career todily. Still cmbed-
rlcd in the projccI system is the ideology tllat
scicntilic rescitrch is an amateur vocaIiori--
a discrclionary incidenLil (0 teaching-to
which Ihc invcsligator can rchirn after ;I brief
Iling. I don't know how else to understand
the preoccupation of the NSF with sunmier
salaries as its avcnuc of support of princi-
pill investigators. Perhaps even t0 a falllt-
one could argue about that-research is no
longer an ancillary function of the univcr-
sity: it is Ihc principal criterion of rccruit-
incrit tu our major universities. I have heard
SOIIIC ngcncics brag Lhat the average dura-
lion of grant support was .&years-that
was supposed to be an index that everybody
could gel a ride on Ihc Irollcy car. They had
6                        63989 by ISI 0 CIJII~CNT CONTENTS@
made no enquiry and obviously could knov
little about what happened after they hat
been pushed off for the new crowd, nor the
waste entailed in that seesaw style.
These frictions first frustrate, then detc
many young scicntisls. I am not aware 0
other than anecdotal evidence that man)
gifted students arc turning away from sci,
cntific careers in anticipation of these prob.
terns. The evidence is clear that very feu
MDs now are willing to embrace the risk!
of a research career as against the incentive:
of a specialty practice (and against a back-
ground of debt for paying for Ihcir MD cd.
ucation that puts them under cxircmc bur.
den). While most of the emphasis, perhap:
correctly, has been placed on the dcclinc 01
secondary and undergraduate education ir
scicncc, thcsc motivational factgg,shouk.
1101 be ignored.
The PhD graduate or MD contemplating
research must look forward to a lifelong cn-
rccr of seeking project grants. His most
promising years may be `those in graduate
school and as a postdoctoral fellow when hc
or she at lcast has the administrative and fi-
nancial sheher of an established laboratory.
WC should not lose sight of the often con-
tradictory demands on the scientific person-
ality: antitheses such as imagination vs. crit-
ical rigor, iconoclasm vs. respect for estab-
lished truth, humility and gcncrosity to col-
leagues vs. arrogant audacity to nature, cf-
ficient specialization vs. broad interest, do-
ing experiments vs. reflection, ambition vs.
sharing of ideas and tools-all these and
more must be reconciled within the profcs-
sional persona. They arc intrinsic to Ihc m-
turc of science. We should work hard to
avoid piling'on gratuitous stresses that dis-
courage, even dctcr, some of the worthiest
young people seeking scientific careers lo-
day. They are perhaps most clearly telling
in the trepidations of well-qualified minor-
ities about entering graduate research and
careers in science, compared to the safe
course of law, business, or medicine.
A far-reaching reconstruction of the fed-
eral-university relationship probably exceeds
realistic goals and certainly would require
still more extensive deliberation. It appeared
to be working admirably from about 1950
to 1965, and, while the high rates ofannual
increase in appropriations cannot be repli-
cated, some other features perhaps can. This
approach has the merit of replicating exper-
iments already done within the corporate
Rlcrnory of granting agencies.
Some essential features include
a. Above all, recognition that an insti-
tution(`s administration) is a processing
center for flows of resources, not a pri-
mary fount. The "partnership" simile
(of govcrnmcnl and university) is a con-
structivc image, but it may bc mislcad-
ing about the revenue-raising capabili-
ties of the partners.
It is clcmentary but still must be cx-
plained to grantors (public and private)
that whatever the grant system does not
provide can only bc compcnsalcd for by
(i) taking rcsourccs away from
  another activity
(ii) discovering other sources
(unlikely!)
(iii) shrinking the program
Suggcslions that "Ihc insliIuiion
should pay for .x.. *' arc rarely accom-
panicd by informed mandates as IO Ihc
sources thaI should bc tapped. Faculty
should not be excessively burdened with
factual knowledge about administrivia;
indeed they are often equally ill-in-
formed about this principle, c.g.. in dis-
cussions of indirect cost recovery. Com-
plex institutions, like academic medical
centers, may need IO improve their own
cost accounling for their own awareness
of the cross-flows, and many questions
doubtless can and should be asked about
them. This oversighI of institutions'
policies is not well done by ad hoc
demands around single, vulnerable proj-
ects on the part of agencies that will not
share responsibility for the reconstmc-
tion that will bc entailed.
b. Restoration of emphasis on the crc-
ativity of individual investigators, raIhcr
than the substance of a research propos-
(11, as the central criterion of merit. Re-
CURllENT CONTENTS@   01989 by ISlO                                 7

search is after all a foray into the un-
known and unpredictable. The skills
needed are, above all, those for impro-
visation in the face of unexpec1ed dis-
covery or disappointment. Those skills
arc not evenly distributed, and a carcful-
ly thought-out proposal is importan tcs-
timony about them. That writing cannot,
however, substitute for proven and sus-
tained accomplishment and, especially,
for research of an exploratory (versus
exploitative) character. It is infuriating
to see critiques worded like "The inves-
tigator has not demons1ratcd [in ad-
vance] that he can [discover such and
such]" addressed to individuals who
have repeatedly surprised the scientific
community (and themselves) with their
prior innovations. No wonder that many
innovative minds now boodeg their most
creative ideas under the cover of "sure-
thing" applications or, as a variant,
write their proposals around work al-
ready completed. And what a was~c that
their ingenuity should be so cxpendcd!
The implication that an investigator
should "know what he is doing" before
being worthy of a grant flies in the face
of the actual history of the most creative
discovery. How would a project propos-
al to NSF have fared that looked to cx-
plot-c the high-temperature superconduc-
tivity of ceramics? And I will aver in ret-
respecting about my own career since
1946 that none of my own most consc-
quential discoveries had been telc-
graphed in project proposals beforc-
hand. About the most important matters,
we are always too ignorant in advance
to spell out the discoveries we might
make.
A change of culture, or rather a regres-
sion to the 1960s era of the National Insti-
tutes of Health and NSF and the 1950s of
the Office of Naval Research, will not hap-
pen spontaneously nor readily. The bureau-
cracies of most institutions and agencies
have become ever more professionalized,
8
viz., as professional administrators, and
only those rare individuals who have had
personal experience of creative scientific re-
search are likely 10 have the skill and expe-
ricncc to know how to oversee these changes
of outlook-a problem especially taxing for
the middle, i.c., working, levels of
management.
We then have 10 think of the most cffcc-
tive managerial devices to work these
changes without entailing the reeducation of
hordes of effector agents. My candidate is
one fell swoop of administrative fiat, name-
ly, a mandate that grant awards again bc typ-
ically for five to seven years. This would
reduce the administrative load of reviewing
grant proposals, and likewise, on the inves-
tigators, especially if there were a period of
grace for the more gradual phasedown of a
nonrenewable project. Reducing the now in-
tolerable workload of review would con-
serve the precious resource of cornpclcnt
peers. 11 migh1 also enable a discourse bc-
twcen applicant and reviewers that is now
rigid and full of mutual misunderstanding.
Our current practice is vicious beyond imag-
ination, once one thinks about it. If there are
questions arising in the review of a project
applicalion, the supplicant will hear about
then1 only after the peer panel has met and,
often, only after a deferral that will have
caused incalculable trauma. The straitencd
bandwidth of communication, the fantasies
[ha1 too often underlit the judgments of the
peer-review group without correction, these
badly need reform wi1h the help both of
more human-scale procedures and of tech-
nologids like electronic mail and file main-
tcnancc. Our other gatekceping systems,
whose of refereed publications and of facul-
ly appoinfmenls, generally give more inti-
mate contact with [he submitter or more
limely feedback and access to other op-
lions-other reviewers, or other gates.
Meanwhile the current research project sys-
tem gives disproportionate rewards to the
Srantsmcn, those most skillful at verbiage
for manipulating the system indepcndcnt of
~he inherent scientific merit of their ideas.
I am less sympathetic with the claim that
these s1resscs in any way justify the incidents
~)1989 by ISI 0 CIJHAENT CONTENTS@
of fraud and misrcprcsentation in science,
each of which is so loudly advertised in the
media. It may be, however, that the current
system is attracting carecrisls inlo science
impelled more by grantsly skills than their
love for problem-solving for human bcnelit
and for truth. WC must be careful to return
to these themes as our criteria of judgment.
The indirect effects of lengthened dura-
tion of awards would bc equally valuable:
it is more difficult for reviewers to slide in-
to micromanaging projects of such duration.
The focus of attention of the applicant would
bc redirected 10 basic goals and of ~hc re-
viewers to the applicant's personal skills.
The time given would allow for opportunis-
tic exploration of unpredictable paths and for
them to face the skepticism of the larger
community.
The principal argument I have heard in
dcfcnsc of the short trolley ticket is the need
to make room for young people. We must
give careful attention to that. Yes, they may
have difficulty competing with established
investigators; they may have li1tle but their
project proposals to present as testimony of
their skills. The perspective of trying to
identify the most capable individuals does
not, I would say, preclude the use of what-
ever testimony is relevant. We c`an of course
give competitive points for youth, if that is
our policy objective. We should keep in
mind, however, that the principal use of
funds in the hands of established invcstiga-
tors is precisely for the support of younger
associates-certainly that has been my lifc-
long experience as student, as professor, and
as administrator. I submit that the working
professor is a better and highly interested
judge of the qualifications of those associ-
ates than is a remote committee; undoubted-
ly, institutions could also enhance their local
rcvicw procedures to assist in those cvalua-
[ions. My own experience was also to have
had the opportunity to earn my spurs and
peer recognition through the work I did as
a research fellow in Professor Tatum's lab-
oratory. This system of apprenticeship has
been institutionalized in the most consistent
fashion in my present institution, The
Rockefeller University, and there is abun-
CURRENT CONTENTSB   01989 by ISI@
Jant his1orical evidence that it works very
well. Finally, if we do really mean that the
typical scientific career is going to be trun-
cated in 7, cvcn in 15 years, we really had
better at1end to all of the other insidious im-
plications this has for the tenure system of
the university.
The extreme, of lifelong tenure of re-
starch support, I do not advocate, even
though that works reasonably successfully
in systems like the British Medical Research
Council and the intramural programs of gov-
crnment and of industry. There is some in-
tcrval of recurrent accountability that must
be optimal in balancing the stress of per-
formance with the leisure and security for
careful reflection; a seven-year cycle should
be about right to keep track of the changing
seasons of a scientific life. It is curious that
many research managers who arc sluggish
to respond 10 my pleas arc themselves per-
mancntly ensconced in their own bureaucrat-
ic niches. I don't advocate that they be pu1
on a two-year leash to prove their perfor-
mance--that would compound the disaster
of short-run bottom-line accountability: a
theme whose consequences for our industrial
economy have been all too evident and cer-
tainly contributed to...Black Monday. But
I hope they will be less insouciant about
"keeping people on the trolley car" for an
average total period that should be a single
episode.
These cries in the wilderness have not
gone utterly unheeded. The directors in our
audience can give you details of their agen-
cies' recent initiatives with experienced in-
vestigator awards and with lengthening the
terms of grants and other simplifications of
their procedures.
Program managers should also be allowed
more flexibility to keep expiring grants
"alive" for intervals long enough to allow
the threshing out of misunderstanding or of
other occasional but apparent failures of ob-
jective peer review. That flexibility is itself
an administrative burden, but it will be more
tolerable against the background of seven-
year than of two-year awards. Finally, as
a university administrator I would frequent-
ly have won the bet, if I could make it, of
9

placing funds on a project on the gamble that
it would be eventually renewed. Some
means should be found for the rctrospcctive
reimbursement of such gambles when they
are in fact legitimated by later reexamina-
tion. That is not merely fair-dealing: it also
enables and encourages insightful manage-
ment on the part of the university adminis-
tration. Of course I have to make such gam-
bles anyhow, but with short shrift for ex-
plicit reimbursement when I am right, in-
tcndcd to offset (the hypothetical case) when
1 am too optimistic. In fact, I can't remem-
ber the last time an investigator that I grub-
staked didn't "get back on the trolley car";
the net cffcct is almost always just a lot of
lost energy (and a dwindling of rcservcs).
Industrial contractors have access to risk
capital, invested as against expectation of fu-
ture profit, that is denied to not-for-profit
institutions. The mcasurcs just suggested arc
in the spirit of many others that would rc-
ward institutional as well as personal skills
in the management of creative science. The
present system of grant funding not only
makes no provision for that risk capital, it
subjects what there is to constant attrition:
unilateral flows from cost sharing, incom-
plete indirect cost recovery, infrastructural
costs, the whole system of faculty co~npcn-
sation that exchanges modest salaries for
lifelong job security. Not allowable as "in-
direct costs" are the career-supporting bur-
dens, attending to the gestation and early
nurture of academic investigators, start-up
and tide-over expenses, even the terminal
care that is part of the system's social
contract.
We should jealously guard the pluralism
in government support of science that is one
of our greatest safeguards against monumcn-
tal and monolithic error. One agency can ex-
periment and offer cuts to improving the
system for others.
4. Wc trtusl slum rcspotr.sildi/y.
The entire burden of renovation of the rc-
search environment' should not and cannot
rest solely on federal refomr. There is much
IO attend to in our own houses.
10
Unhappily, too many institutions have.
been socialized to accommodate to their de-
pendence on the existing system and with
reduced power their directors have abdicated
what leadership they might still exercise in
the management of research. Such a swccp-
ing generalization is of course subject to no-
table but rare exceptions.
All too often the department has become
the largest unit that sustains much intellec-
tual and academic cooperation. Students
funded from one project can spend sonic
time in another lab in the same dcpartmcnt;
there is no comparable facility across broad-
er reuchcs of the university. Above all the
project funding system has further bolstcrcd
the imperatives of specialization; many able
professors have little expcriencc and little
culture beyond the domain of their discipline
(projects]. The project system further pre-
cmpts the loyalties that might be directed to
one's collcagues and one's institution in
favor of the nationally centralized fount. In
that milieu there is little incentive or latitude
Ibr lcadcrship of any breadth cvcn within
scicncc. Both these structural impediments,
and the rarity of the appropriate talent, make
it cvcr more difficult to install department
chairs, deans, or provosts who arc cognitivc-
ly engaged with the content of the work they
are called upon to administer. WC arc gratc-
ful when their political and human relations
skills sustain some quiet among warring fac-
tions. I'rcsidents, as Steve Muller and Jim
March have lamented, are no longer expect-
cd to do more than raise money and empty
111~ garbage cm Nor arc faculty likely to
be rcsponsivc, when their main task is to get
their grants rcncwed. In consequence of
these (and other) factors, many able scien-
tists will properly refuse to involve them-
selves in formal administrative responsibil-
ities: chairs, deanships, and other exccutivc
positions arc going begging or arc being
filled by people with requisite high talents
other than academic. It dots not follow that
scholarly attainment is a suflicicnt qualifica-
tion for a managerial role; but without it the
exccutivc is ill equipped to make his own
judgment of the merits of his colleagues'
work, and he must struggle to sustain their
01989byISlG' CURRENT CONTENTS@
esteem and his or her authority. This dcprc-
cation of leadership is part of a vicious cy-
cle of anarchy and its associated ills of splin
tering what ought to bc a community of
scholars. We all sham responsibility for the
exertions nccdcd to restore mat communi-
ty, one that includes the tcachcrs, the rc-
searchers, and the administrators.
5. Some r/tough/s 011 "big scicttcc. "
Biology, until now, has rarely faced the
need for mcgatcchnologics to answer its pri-
mary scientific objectives. The human gc-
nomc DNA-sequencing proposal does loom
as a new way of doing business. This is a
structure of formidable complexity: three
billion nuclcotidc pairs of DNA, a full two
meters of double helix if unraveled from a
single cell. This corresponds to about
100,000 gcnc products that will have 10 bc
accounted for. The ultimate reductionism
would be to build an analytical factory that
could complctc the reading of all three bil-
lion units as one technical exercise. A price
tag of a few billion dollars is cited, perhaps
Icss if there is prior investment in new tech-
nology to automate the task. Is it worth the
cost? Undoubtedly! Is it the wisest USC of
that lcvcl of expenditure? I have very grave
doubts! Part of my reservations have to do
with the style of rcscarch it encourages, part
with a misunderstanding about what WC riced
lo learn in "mapping the genomc." We have
by now profound information concerning a
score or so of human proteins; each of them
is at lcast a life's work. At a modest $10
MM each, that would amount to a trillion
dollars for the full set, and obviously WC
must make discriminating selections of tar-
gets before committing to the task. About
100 human proteins arc now discernible as
agents of important biological activity; that
number will soon grow to perhaps 1,000.
These should be the priority list for further
inquiry. It will bc far more important and
more fcasiblc to learn in depth about that
percentile of the human genomc than to have
an exhaustive listing of a sequence of three
billion nucleotides. For these, we will look
CUtlRENT CONTENTS@  01989byISIQ
in detail into regulation, three-dimensional
structure, genetic variability within and bc-
twecn spccics, physiological intcrrclation-
ships, and therapeutic applications. To pur-
sue such enquiries will tnkc much more than
the cnginecring mentality that would apply
a single methodology for a single sweep. II
will need a sense of the organism and a fo-
cuscd expertise on, even fascination for, the
parts under scrutiny. This megaproposal
dots bchoovc us to sharpen a distinction bc-
twccn exploratory and cxploitativc phases
of scientific devclopmcnt. Exploratory re-
starch engcndcrs rcvotutionary brcak-
throughs with new pcrspcctivcs; the agcn-
da for cxploitativc scicncy then bccomcs
fairly obvious. For the latter, cxquisitc
technical skills are to be recruited, but not
too much imagination. Such projects can
then bc fairly readily judged by objective rc-
vicwcrs. There is little likelihood of plans
being disrupted by totally uncxpcctcd dis-
coveries-though this may happen cvcn in
the best regulated laboratory. Prcciscly be-
cause the DNA-sequence paradigm is so
central to modern biology, it dots set the
agenda for almost all of the forcsecablc. the
plannablc rcscarch at least of the next cou-
plc of dccadcs. My fcar is that it may also
submerge new revolutions, not unlike the
ones that initiated us into this phase of the
history of biology.
Other sciences face very different chal-
lenges. Without large tclescopcs, accclcra-
lors, spacecraft, important rcgimcs of the
physical univcrsc remain simply inacccssi-
blc to us. We have had good cxpcrienccs in
national facilities to provide thcsc capabili-
ties to a broad national community. Thcrc
remain serious questions how to relate them
to the life of the university. Much concern
has been exprcsscd that existing departmen-
tal structures frustrate broader and more in-
novative interests-and I have had my own
experience of that. Genetics was certainly
a stepchild at medical schools at the start of
my career, and biochemistry not long bcforc
that, But I question whcthcr larger "ccn-
lers," if brought in top-down, won't aggra-
vate the problem. By their allegiance to ex-
ternal sponsors, they will bc even less ac-
11

countable to, and communicative with, their
colleagues on their own campus. At the
same time they will make inevitable calls on
genera1 resources that will weaken the uni-
vcrsity's flexibility in responding to other
contingencies. WC can answer these con-
cerns (a) with appropriate sensitivity in the
style of administmtion of these centers, and
(b) by stronger internal leadership to con-
travene the splintering of the campus com-
munity into walled enclaves. Otherwise, we
may again lind that today's "new" centers
arc tomorrow's cntrcnchcd resistance to
cvcrchanging horizons.
Anolher challenge to introspection is
whether we are,doing all we can to acceler-
ate "technology transfer" from academia to
industry-a point of special sensitivity in the
midst of today's anxieties about economic
compctitivencss. No one who knows my
own personal history will accuse me of in-
difference to that issue. I will recall an anec-
dote about my professor. Edward L. Tatum.
who complctcd his PhD in bacteriology at
Wisconsin just 50 years ago and was facing
a de&ion where to work. He was urged to
take a position at Iowa, to look into the then
"hot" lield of the microbiology of butter,
one'of manifest practical importante. Instead
he went to Stanford, to work with G.W.
Ueadle on the eye pigments in fruit flies.
That became translated within four years
into their Nobel Prize winning work on the
biochemical genetics of Neurospora, indu-
bitably one of the pri'ncipal foundations of
today's biotechnology. It would have been
tragic were any industry to have had a veto
in deciding what would truly be of grcatcst
industrial consequence. My own expericncc
has been consistent with that theme, that the
u&ersities accept the difficult charge of
leadership in pointing out where tomorrow's
industries will find their greatest opportu-
nities, many of them in the hands of corpo-
rations that will need new birth ccrtili-
cates-and so will not yet be at hand as the
visible contemporary partners at the time the
research is conceived.
The wisdom to oversee these complex
technical relationships is still another chal-
Icnge to the academic leadership of the fu-
ture. Good luck.
November 27, 1989
Volume 29 Number 48
Physical, Chemical -
& Earth Sciences