Di­rected Sci­ence, Cu­rios­ity-Dri­ven Sci­ence, and Strik­ing the Bal­ance

It is our plea­sure to con­tinue our tra­di­tion of host­ing a few re­flec­tions from the new pres­i­dent of the ASM.

by Jeff F. Miller

Af­ter nearly three months as pres­i­dent and one year as pres­i­dent elect, what amazes me most about the ASM is the breadth and depth of our ac­tiv­i­ties. We lit­er­ally span the globe, with am­bas­sadors in 54 coun­tries and out­reach pro­grams in Africa, South Amer­ica, and Asia fo­cused on build­ing lab­o­ra­tory ca­pac­ity for tu­ber­cu­lo­sis, HIV, and other in­fec­tious dis­eases. The 14 Jour­nals we pub­lish are rein­vent­ing them­selves to re­main vi­tal in an elec­tronic world, and mBio, our newly launched pre­mier pub­li­ca­tion, scored an im­pres­sive im­pact fac­tor of 5.3, less than two years af­ter pub­lish­ing its first is­sue. Our mem­ber­ship num­bers are up nearly 2% from last year, with the largest in­creases in stu­dent and in­ter­na­tional mem­bers, and a new tiered struc­ture will make it eas­ier and more at­trac­tive to join. The Gen­eral Meet­ing has re­cently un­der­gone a meta­mor­pho­sis and I am pleased to re­port that to­tal reg­is­tra­tion for 2012 was the high­est since 2008, with over 9,300 at­ten­dees. The Acad­emy of Mi­cro­bi­ol­ogy con­tin­ues to ex­am­ine ways that mi­crobes can pos­i­tively im­pact en­vi­ron­men­tal and hu­man health, as ex­em­pli­fied by their re­cent col­lo­quium on "De­sign­ing Drugs that Last", and our Pub­lic and Sci­en­tific Af­fairs Board has been work­ing tire­lessly to ad­vo­cate on our be­half to agen­cies and law­mak­ers through­out Wash­ing­ton. Their cur­rent ef­forts to lobby against across-the-board cuts in dis­cre­tionary spend­ing, as stip­u­lated in the Bud­get Con­trol Act of 2011 and slated to be en­acted on Jan­u­ary 2, 2013, are crit­i­cal for pre­vent­ing a po­ten­tially crip­pling blow to the na­tions sci­en­tific re­search en­ter­prise. This is just a small sam­pling of re­cent ac­com­plish­ments and ac­tiv­i­ties and for more in­for­ma­tion please see our web­site at www.ASM.org. It is in­tended to il­lus­trate the in­flu­ence and reach of the ASM and its po­ten­tial for ad­vanc­ing our field, which brings me to the point of this ed­i­to­r­ial.

As a ba­sic sci­en­tist, there are few is­sues of greater in­ter­est or rel­e­vance than fed­eral sup­port for re­search and train­ing. Al­though we would all em­brace ma­jor in­creases in bud­gets for the NIH, NSF, and other fund­ing agen­cies, this seems un­likely given the cur­rent cli­mate, and maybe a bit naive. There is, how­ever, a "de­gree of free­dom" that de­serves to be ex­plored, and it in­volves not the ab­solute num­ber of dol­lars, but how the money is be­ing spent. To pick an ex­am­ple of rel­e­vance to many ASM mem­bers, the NIH re­cently re­leased a con­cept state­ment for a pro­gram de­signed to build on the Re­gional Cen­ters of Ex­cel­lence for Biode­fense and Emerg­ing In­fec­tious Dis­eases Pro­gram, which will sun­set in 2014. The ini­tia­tive will sup­port multi-in­ves­ti­ga­tor, mul­ti­dis­ci­pli­nary trans­la­tional re­search cen­ters fo­cused on gen­er­at­ing, val­i­dat­ing, and ad­vanc­ing ther­a­peu­tics and vac­cines, with sig­nif­i­cant over­sight by pro­gram of­fi­cers. This is ad­mit­tedly an ex­treme case, but it raises two gen­eral is­sues. The first in­volves "man­aged big sci­ence," for want of a bet­ter term, and the sec­ond in­volves the bal­ance be­tween ba­sic re­search and ap­pli­ca­tions.

The need for trans­dis­ci­pli­nary, multi-in­ves­ti­ga­tor pro­grams that tackle big ques­tions in bi­ol­ogy is clear and well jus­ti­fied. The breath­tak­ing in­sights from the Hu­man Mi­cro­biome Project pro­vide a beau­ti­ful il­lus­tra­tion of the cen­tral im­por­tance of mi­crobes and mi­cro­bi­ol­ogy, and they would not have been pos­si­ble with­out a mas­sively in­te­grated ef­fort. Big sci­ence is im­por­tant but it comes at a sig­nif­i­cant cost, and it seems rea­son­able to ask how these ef­forts should be de­signed, man­aged, and bal­anced to pro­duce the great­est value from our re­search in­vest­ment. Re­quests for pro­pos­als in­volv­ing large teams of in­ves­ti­ga­tors and cor­re­spond­ingly large bud­gets have be­come com­mon­place. These are de­signed by fed­eral agen­cies with spe­cific goals in mind and they are of­ten highly pre­scrip­tive, pre­cisely out­lin­ing top­ics and ap­proaches to be in­cluded, and ex­cluded, along with ad­di­tional re­quire­ments and stip­u­la­tions. Is this the best and most cost-ef­fec­tive way to fa­cil­i­tate col­lab­o­ra­tive sci­ence? Has the ap­proach be­come too "top-down" and should op­por­tu­ni­ties be de­signed to let even bet­ter ideas for big sci­ence "per­co­late up" from the re­search com­mu­nity? What is the op­ti­mal bal­ance be­tween tar­geted re­search and in­ves­ti­ga­tor-ini­ti­ated in­quiry? And per­haps most im­por­tantly, are di­rected ap­proaches the best way to mar­shal the cre­ativ­ity and in­no­va­tion re­quired to achieve grand chal­lenges, or do they sti­fle it?

Re­turn­ing to the biode­fense ex­am­ple cited above, the pro­posed ini­tia­tive will fo­cus al­most ex­clu­sively on ap­pli­ca­tions in the form of ther­a­peu­tics and vac­cines. The im­por­tance of ap­pli­ca­tions that ben­e­fit so­ci­ety are un­de­ni­able, and they are an es­sen­tial com­po­nent of the jus­ti­fi­ca­tion for pub­licly sup­ported ba­sic re­search. But there is a grow­ing per­cep­tion in the re­search com­mu­nity that the pen­du­lum has swung so far in this di­rec­tion that it places dis­cov­ery at risk. Cu­rios­ity-dri­ven re­search has and will con­tinue to pro­vide the foun­da­tion for fu­ture ap­pli­ca­tions, and by ex­ten­sion our abil­ity to in­no­vate and com­pete as a na­tion. This is­sue was re­cently con­sid­ered in an ed­i­to­r­ial by Fran­cis Collins, di­rec­tor of the NIH. His con­tention that ba­sic re­search has not been com­pro­mised at the ex­pense of trans­la­tional ef­forts may en­gen­der de­bate, but his con­clu­sion should not. In it he states that "In this time of se­vere bud­get con­straints, Amer­i­cans need to know that today's ba­sic re­search is the en­gine that pow­ers tomorrow's ther­a­peu­tic dis­cov­er­ies... and they need to hear it from all aboard the bio­med­ical re­search ship." Herein lies the chal­lenge. As any ba­sic sci­en­tist that has tried to ex­plain their work to a non-sci­en­tific au­di­ence knows, it is much eas­ier to ar­tic­u­late the im­por­tance of a po­ten­tial ap­pli­ca­tion than to con­vey the es­sen­tial na­ture of pure, unadul­ter­ated, cu­rios­ity-dri­ven re­search. But if we don't do it, who will?

Ques­tions re­gard­ing the op­ti­mal bal­ance be­tween di­rected sci­ence and in­ves­ti­ga­tor-ini­ti­ated in­quiry, and ap­plied vs. ba­sic re­search, are un­de­ni­ably com­plex. They im­pact not only mi­cro­bi­ol­ogy, but life and bio­med­ical sci­ences and be­yond. As the largest sin­gle-life sci­ences or­ga­ni­za­tion in the coun­try, and one that has earned tremen­dous in­flu­ence and re­spect, I sub­mit that the ASM is poised to con­tribute to this de­bate in an in­formed and pro­duc­tive way. In ad­di­tion to con­tin­u­ing our vi­tal ef­forts fo­cused on ad­vo­cat­ing for sup­port for NIH, NSF, CDC, and other agen­cies, I be­lieve it is time to de­vote in­creased at­ten­tion to un­der­stand­ing how avail­able re­search dol­lars are be­ing spent, and to con­sid­er­ing how in­vest­ments can be lever­aged to in­sure that a ro­bust pipeline of ba­sic dis­cov­er­ies will be avail­able to sup­port ap­pli­ca­tions of the fu­ture. If done right, our col­leagues in Wash­ing­ton will likely pay at­ten­tion, and they may even fol­low our ad­vice. It is equally es­sen­tial to use our com­mu­ni­ca­tions ca­pa­bil­i­ties to more ef­fec­tively and broadly con­vey the im­por­tance and ex­cite­ment of cu­rios­ity dri­ven re­search and how it fa­cil­i­tates trans­la­tion. Our ed­u­ca­tional ef­forts can also be fo­cused on pro­vid­ing stu­dents and sci­en­tists with the skills to ex­plain what we do and why we do it to non-sci­en­tists, in a way that en­gen­ders un­der­stand­ing and en­thu­si­asm as op­posed to con­fu­sion. The ASM has re­mark­able re­sources to draw upon and these ef­forts will ben­e­fit from the con­certed ex­per­tise of our Pub­lic and Sci­en­tific Af­fairs Board, Com­mu­ni­ca­tions and Press, the Acad­emy of Mi­cro­bi­ol­ogy, our Ed­u­ca­tion and Pub­li­ca­tions Boards, and other arms of the so­ci­ety. ASM should also ex­plore strate­gic part­ner­ships with like-minded or­ga­ni­za­tions that have sim­i­lar goals and syn­er­gis­tic ca­pa­bil­i­ties. In ad­di­tion to ask­ing for in­creased re­search fund­ing, it seems pru­dent to fo­cus on max­i­miz­ing the yield from sup­port we al­ready have. The vi­tal­ity of our field may de­pend on it.

Jeff F. Miller is Pro­fes­sor and Chair of the De­part­ment of Mi­cro­bi­ol­ogy, Im­munol­ogy and Mol­e­c­u­lar Ge­net­ics at UCLA, and Pres­i­dent of the Amer­i­can So­ci­ety for Mi­cro­bi­ol­ogy. His lab­o­ra­tory stud­ies mech­a­nisms of bac­te­r­ial patho­gen­e­sis and the gen­er­a­tion of di­ver­sity in bac­te­ria and phage. The opin­ions ex­pressed in this ar­ti­cle are his own and do not nec­es­sar­ily re­flect the of­fi­cial po­si­tion of the ASM.