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