attempting to motivate our children to go to bed at a reasonable time , parents have for generations invoked these three time - honored rewards .
health is the absence of something , namely sickness , and is only fully appreciated when we no longer have it . yet , when we are really sick , health becomes our paramount concern .
few of us would choose to be a wealthy , wise man or woman if the price was advanced alzheimer 's disease , terminal cancer , or crippling arthritis .
in this context , we have a major problem as a society . despite our amazingly advanced technologies in such areas as communication , space travel , and transportation
why is it that our capacity to innovate in biomedical sciences seems to lag so dramatically behind our innovation capacity in aircraft design , for example ?
we serve as directors of the california institute for quantitative biology ( qb3 ) , which seeks to promote innovation in the biomedical sciences . at qb3
, we look closely at the impediments to improving health through technology and explore solutions to this problem .
we are convinced that many answers could be found in our research universities if they were restructured .
they need to be innovative in how they manage their science , as well as in how they perform it .
universities are without peer in their ability to discover the fundamental principles of science and are responsible for much innovation in our society .
the creativity and nimbleness of their science is unfortunately not matched by equal creativity and nimbleness in administration and management .
although service innovation is now widely seen as contributing to economic growth and addressing societal needs as effectively as science innovation , universities in general continue to operate using time - honored , unchallenged principles . this must change .
we need to evaluate how effectively we perform our public mission , and whether our exclusive focus on specialization precludes our usefulness .
to know what to change , we have to go back to the way our biomedical  industrial complex is constructed .
we have come a long way from the days when science was done by a gentleman scientist in a room in his mansion , supported by his own funds or those of a generous friend .
nowadays , governments put a significant part of their gross domestic product into supporting research and development .
much of this investment , about $ 50 billion per year in the united states alone , goes to our research universities .
governments justify this use of taxpayers money by pointing out , correctly , that unfettered research activities are the most effective way of fostering the innovation needed to address current and future challenges to society .
scientists also are motivated by the sheer beauty , elegance , and excitement of fundamental discovery , but this is an acquired taste , not usually shared by the general public !
what society does expect are results that meet its needs . to get societal value from university research
if investors and manufacturers see a potential market for an innovation , then the discovery moves efficiently out of the lab and into the marketplace .
not only does society get something it needs , as measured by its willingness to pay for it , but the manufacturing and marketing process creates jobs and economic growth .
the social contract of science , therefore , is that university scientists are given the freedom to pursue their research interests , supported by taxpayers funds , because the taxpayers have been convinced that potentially commercializable discoveries will be made , which will result in new products and economic growth .
the contract specifies roles for the three stakeholders : government , universities , and the private sector . in the life sciences , the system is not working well for all three stakeholders .
government is questioning whether it is getting sufficient value when its investment in university research generates one start - up company per $ 100 million and one patent license for every $ 12 million ( battelle technology partnership practice , 2010 ) .
university scientists are being told that they must stop pursuing fundamental biological principles and direct their research toward specific societal needs .
venture capital , especially seed funds for life sciences innovation , is drying up ( phillippidis , 2011 ) .
finally , the powerhouses of the biomedical industry , the large pharmaceutical companies , have few new products coming to market and are looking at a drop in income of over $ 100 billion in the next few years ( begley and carmichael , 2010 ; wilson , 2011 ) .
the crisis in the biomedical innovation world is what is frequently called a  wicked problem ,  one that is challenging to solve because it involves the interaction of disconnected entities . to solve this crisis requires stakeholders to interact with one another more productively .
we believe that research universities are ideally suited to solve wicked problems but need to adjust their operating structures to do so .
a few years ago , the petroleum giant bp awarded a consortium of universities led by berkeley the largest grant in university of california history , $ 50 million per year for 10 yr . despite the well - publicized travails of bp , that commitment remains firmly in place .
graham fleming , now vice chancellor for research at berkeley but earlier a qb3 leader and one of the architects of the european bioinformatics institute consortium , explains it this way .
manufacture of biofuels is a classic wicked problem , requiring for its solution the expertise of many stakeholders with disparate backgrounds and nonoverlapping goals .
manufacturing biofuels requires economists to verify a market , chemical engineers to design refineries , industrial microbiologists to optimize the enzymatic breakdown of biomass , botanists to select the optimum biomass , agronomists to define the growing regions , and hydrologists to provide them with adequate water .
even a company with the resource base of bp does not have quality expertise in all these fields .
in contrast , universities do have the requisite talent , but the trick is to network the faculty , creating a team .
the berkeley leadership skillfully assembled a  biofuel ecosystem  and so deservedly won the bp competition for the $ 500 million .
this example demonstrates that , with inspired leadership , universities can assemble teams to address wicked problems .
an obvious challenge is whether creation of an analogous  bio - innovation ecosystem  might help address the current troubles in the life sciences industries .
insight into how a  bio - innovation ecosystem  might impact the difficulties faced by the life sciences industries can be garnered by examining the aviation industry .
the pharmaceutical and aircraft industries both invest huge amounts of money and time in creating new products .
aeronautical engineers may not completely understand the physics of wing lift , but they can predict what will fly with remarkable accuracy .
a plane is designed by engineers , built to their specifications , rolled out on a runway , and takes off perfectly .
we have such trust in our aviation knowledge and our engineers that we are not surprised .
in contrast , over 90% of candidate drugs fail completely to do any good when administered to patients during phase i trials ( paul et al . , 2010 ) .
if manufacturing new aircraft were similar to designing new drugs , 9 out of every 10 newly designed planes would crash on takeoff !
an airplane cockpit is crammed with indicators that monitor the status of almost every important function .
if something begins to go wrong , it is quickly detected and the pilot can take corrective actions and determine if they are indeed working .
how do we know whether a drug for alzheimer 's or schizophrenia or cancer is having an effect ?
lacking quantitative biomarkers that reflect the progress of a disease makes it a huge challenge to measure drug efficacy .
as much as the industry needs new drugs , it yearns for biomarkers to precisely measure efficacy and sensitively warn of unwanted toxicities ( editorial , 2010 ) . creating such biomarker sets to monitor a single disease ( e.g. , alzheimer 's progression )
we may scoff at the old theories from galen 's time of balancing the humors by medical intervention , but in truth we are not much more sophisticated now .
to continue the airplane analogy , it is like repairing a defect in an airplane by breaking something else !
the explanation of this paradox is emerging , albeit slowly , as we move from reductionism to looking at the human body as a set of interlocking systems .
aircraft engineers have followed a systems approach for decades and biologists are beginning to follow in their footsteps . until biologists have assembled a systems approach to replace current molecular reductionism , we may have to settle on an empirical strategy to guide drug development , using biomarkers as indicators of benefits and dangers .
successful innovation in the life sciences will require more than assembling teams of academic scientists to develop predictive biomarkers .
it will also require that three entities with fiercely independent cultures and largely nonoverlapping goals have meaningful dialogues with one another .
government , academia , and the private sector need to reconcile their separate goals and work together more cohesively .
a dialogue with the private sector is the obvious way to find out whether a university discovery has practical implications ( silber , 2010 ) .
. universities have poorly defined mechanisms for determining what society , or even the life sciences industry , really needs and so , by default , let research programs be driven by faculty interest , not societal need . for a successful dialogue , the private sector must also have something to learn from the university . what the life sciences industries want is the identification of novel drug targets , disease biomarkers , and disruptive technologies for a start , but few faculty do research pertinent to those wants , even if they are aware of them .
the investment community wants to prowl the halls looking for a juicy academic project that will give impressive returns on investment in a small number of years  a biological google !
the manufacturing companies and the investors are keenly sensitive to regulatory and reimbursement hurdles imposed by government , to tax incentives , and to grants for small businesses . in return
, government wants to hear about the link between scientific innovation and tax revenue , economic growth , and job creation ( national economic council , 2011 ) .
finally , the universities need to confer with government about what fraction of research funding should be targeted for applied versus basic research ( usdin , 2011 ) .
our contention is that the dialogue can be dramatically optimized by creating a university - centered bio - innovation ecosystem .
the structures of the ecosystem will facilitate three - way conversations among the three stakeholders and make those conversations disciplined and productive .
( companies advise government on university funding ; universities give government input on small business grants , innovation zones , and regulatory science ; companies help universities identify unmet needs . )
we argue that this much - needed innovation in the way research universities carry out their mission will pay off in generating more user - driven innovation in the universities , more efficient use of clinical trials data , a marked increase in efficacious drugs coming to markets , more evidence - based regulatory frameworks , enhanced economic growth through job creation , and consolidation of america 's place as a leader in bio - innovation .
the paucity of new therapeutic drugs coming to market can not be attributed exclusively to weaknesses in our pharmaceutical industries .
several concrete steps are suggested : 
 acknowledge that academia must interact more collegially with the two other stakeholders , government and the private sector.recognize that the shortage of new drugs is a wicked problem and that universities are ideal places to solve wicked problems.commit to solving wicked problems by creating networks run by academic generalists who can extract value from our silos of specialization.recruit , reward , and promote academic generalists to coordinate the activities of specialists in the solution of wicked problems.set up criteria that can assess the value of academic generalists . if successful , universities should : foster partnerships between clinical and basic scientists;link academic scientists to industry partners with complementary skills , allowing them to work together to address pressing societal problems;link academics to the resources they need to start up companies;advocate effectively in a nonpartisan manner for improvements in government funding of research and in reimbursement and regulatory policies ; andalert their academic colleagues , both faculty and students , to opportunities that match their research specialties to pressing needs of society . acknowledge that academia must interact more collegially with the two other stakeholders , government and the private sector .
recognize that the shortage of new drugs is a wicked problem and that universities are ideal places to solve wicked problems .
commit to solving wicked problems by creating networks run by academic generalists who can extract value from our silos of specialization .
recruit , reward , and promote academic generalists to coordinate the activities of specialists in the solution of wicked problems .
if successful , universities should : foster partnerships between clinical and basic scientists ; link academic scientists to industry partners with complementary skills , allowing them to work together to address pressing societal problems ; link academics to the resources they need to start up companies ; advocate effectively in a nonpartisan manner for improvements in government funding of research and in reimbursement and regulatory policies ; and alert their academic colleagues , both faculty and students , to opportunities that match their research specialties to pressing needs of society . besides supporting research and education in the quantitative biosciences ,
qb3 has led an aggressive effort to create a small  academy of generalists  devoted to solving wicked problems and to creating a bio - innovation ecosystem that includes government and the private sector .
although it is still more a work in progress than a blueprint for success , our experience to date suggests there is a role in universities for scientists who are willing to go beyond the comfort zone of their own special expertise .
linking the expertise of others to find solutions to pressing problems can be equally rewarding .
 academia should be willing to shoulder some of the responsibility for the current dearth of new therapeutic drugs . 
 our research funding is predicated on the assumption that it will bring value to society , but our emphasis on scientific specialization hinders our ability to add value when a broader vision is required . 
 a solution is the creation of an academy of science generalists motivated to bring together clinical and basic scientists , academia and the private sector , government legislators and industry . 
 a small investment in academic generalists could yield benefits far beyond its modest cost . 