The Institute for Venture Science (IVS) invests in the high-risk, high-reward approaches to investigating innovative ideas that show promise of leading to important scientific breakthroughs.

Acknowledging the need for scientific breakthroughs, some scientific granting agencies have begun taking measures to increase their portfolios of “transformative” research. Transformative research has the potential to bring radical advances. Current agencies, however, are not set up to deal with the most critical obstacle to realization: the reluctance of the scientific community and other stakeholders to entertain ideas that challenge their long-held views. Challenges are often perceived as antithetical to the community leaders’ best interests and, hence, few transformative ideas ever ascend to realization in a reasonable time frame, no matter how compelling the case may be.

The IVS Operating Plan overcomes this obstacle. It does so by funding multiple teams of scientists who independently pursue the same unconventional approach to an intractable problem, or the same alternative to an entrenched way of thinking. This strategy builds a critical mass rapidly.

Grants are awarded following rigorous review. The challenger and defenders of the status quo present their arguments to a panel of disinterested scientific observers, who decide whether the challenge is meritorious. The most highly ranked proposals are funded liberally, enabling multiple laboratories to pursue the same challenge theme. In the hoped-for event that independent efforts produce compatible results, this multiplicity creates a critical mass that cannot be ignored; challenge and orthodoxy compete on equal footing and if the challenge prevails, then the result qualifies as a realized breakthrough, which might well lead to a paradigm shift or even a revolution in scientific thinking.

The workings of the Institute are guided by a Board of Directors and run on a day-to-day basis by an Executive Director. The Director reports to the Board, whose Chair in turn reports to Institute donors and partners. Following the current ramp-up period, the Institute intends to operate on a $1B per year budget, drawn from a permanent endowment.

The Institute’s investments in fundamental science are expected to bring multiple, high-level breakthroughs. These scientific breakthroughs will almost certainly lead to new technologies, which should produce a healthy return-on-investment, similar to commercial venture investments except that the return will be enjoyed by all of humanity, in perpetuity.

(Note: Executive Summary revised from a version submitted to President Obama July 2010.)

Since the time scientific granting agencies were created more than half a century ago, the outpouring of scientific data has been staggering. The tree of knowledge has grown countless limbs and branches, some pointing in directions never dreamed possible. Yet, along with this phenomenal growth have come problems.

The most serious of these problems is the recent dearth of fundamental scientific breakthroughs, i.e., of game-changing discoveries that have had a profound impact on our society. Many scientists acknowledge this problem. Others, including non-scientists, impressed by the massive outpouring of data and optimistic media releases, sense that impact must certainly be imminent. However, when pressed to cite half a dozen scientific discoveries (not technical advances) made over the past several decades that have already succeeded in changing the world, most cannot cite more than a handful, despite the astonishing mass of experimental data. Realized breakthroughs have been in short supply.

Recognizing the gravity of this problem, government granting agencies have begun taking some measures to deal with it, especially in the US.

The National Science Foundation, in response to a letter-writing campaign to open the system to fresh ideas, instituted the “Frontiers in Biomedical Research” program in 2003. Shortly afterward, the National Science Board, which runs the Foundation, set up a commission to deal more extensively with the issue of transformative research. Following two years of deliberations and hearings, the Board issued a unanimously approved report in 2006. The Board concluded that the dearth of transformative research output was a “problem of great seriousness.”

The National Institutes of Health has treaded along a similar pathway. In response to another letter-writing campaign from scientists in 2003, Dr. Ellie Ehrenfeld, then Director of the NIH Office of Scientific Review, set up a workshop in 2004 to deal with the matter of scientific conservatism. Three recommendations came forth. One was adopted by the NIH Director to become the NIH Director’s Pioneer Award. Another, more recent (December’ 07) NIH-sponsored workshop on “Fostering Innovation” brought many recommendations from a panel of distinguished scientists that included two Nobel Laureates. A new “NIH Director’s Transformative Award” came into being.

These decade-long campaigns and workshops have begun changing the face of the granting organizations. Both aforementioned organizations contain an increasing number of “transformative” programs, designed to identify and fund research that has paradigm-shifting potential. The US-Israel Binational Science Foundation has set up a similar program. Whether these programs are yet working as effectively as intended is a matter of debate. But what is clear is that the agencies themselves recognize that the breakthrough rarity problem exists, and that something needs to be done about it if science is to advance at a pace that at least keeps up with the list of unsolved threats to humanity’s future.

The IVS tackles the breakthrough-scarcity problem head on. While some grant programs profess to give risky ideas a chance, that is merely the first step. A critical second step is to advance the most meritorious of those ideas into active competition with the prevailing views — to assure that the best of transformative thinking can gain enough traction to draw the attention of the scientific community. Until that happens, even the most compelling of revolutionary ideas will languish in obscurity, as many now do.

Thus, getting the attention of the scientific community constitutes a central goal of the IVS. Fresh thinking is necessary because scientists under challenge will often resist. Any questioning of their belief systems may be experienced as threatening — not only to their sense of foundational stability, but also to their scientific standing. Imagine leaders in physics confronted with compelling evidence for a form of energy previously unknown. Exciting, perhaps, but also destabilizing, and often threatening.

As a result, temptation exists to dismiss the challenger with a mere wave of the hand. We may even hear “pseudo-science” or “crackpot science.” Such casual dismissal lends reassurance to members of the group under challenge; they can feel secure in their thinking. Everyone is happy — except the challenger, who cannot gain traction even for a potentially earth-shaking proposal with sound rationale and supporting evidence.

The strategy of dismissing challengers is not new. It is a predictable feature of human nature. In the past, science challengers could sometimes succeed; they could prevail because achieving success was merely a matter of convincing an intimate group of influential scientific leaders; they were few in number. Achieving success today, ironically, has become more formidable because the scientific enterprise has grown so massive. It is no longer a matter of convincing a few, but of convincing masses of scientists, naturally reluctant to be convinced. Those scientists control public opinion, and, also funding. It’s no surprise that few potential breakthrough ideas ever advance to see the light of day.

Breakthrough ideas are not in short supply. Those taking the trouble to look will find meaningful alternatives to conventional thinking distributed throughout the domains of science, some of them rich with promise. All but a few are ignored or repressed by the prevailing orthodoxy, either because of perceived threats to self-interest, or because of a cultural bias that fundamental discoveries are no longer possible. These unconventional schools of thought represent potentially ripe fruit, waiting to be plucked.

Examples of plucked fruits do exist; but mainly from some years back:

• The concept of “jumping genes” pioneered by Barbara McClintock. Shunned by colleagues and left in isolation for decades, McClintock was ultimately vindicated in the early 1980s with a Nobel Prize. Her work on transposons was finally recognized as one of the momentous discoveries of modern biology. Even in the popular literature, McClintock stands as a symbol of dissent against an intolerant establishment.
• Peter Mitchell won the Nobel Prize in 1978 for chemiosmosis, which describes how cells transduce energy in the form of ATP. Like McClintock, Mitchell was for many years ridiculed as an eccentric iconoclast. Yet, because of his personal wealth, he could press on in his home laboratory. Eventually, his view prevailed, and this eccentric iconoclast became something of a scientific folk hero.

These two examples — crazy ideas turned received wisdom — are representative of the many ideas currently out there. Those two concepts managed to succeed, but the overwhelming majority of them have not succeeded — some surely because of their unworthiness, but others because, for the reasons mentioned above, they could not manage to attract the attention of the scientific community. They remain obscure. These high-risk ideas constitute low hanging fruit, well hidden in secret gardens, and insulated by high fences. Those fruits remain to be plucked.

Gathering this potentially rich harvest is a challenge not unlike that faced by venture capitalists. Those investors bet on a series of promising ideas, enabling each one to bridge across the dreaded “valley of death.” A significant fraction will fail, while others may succeed — some so magnificently (Amazon, Google, luggage-with-wheels) that the overall strategy ultimately wins.

For fundamental science, a similar risk-taking strategy can harvest some of the many promising ideas that now languish in obscurity. The IVS approach parallels the venture capital approach, except that the venture here is science, not business. We seek out low-hanging scientific fruits. We nurture them to maturity, taking them to the marketplace for fair competition with prevailing schools of thought. There, the path forward can be determined by merit, not by politics or sociology. The results can be just as powerful as those seen in the commercial sector. Even if in number they may be relatively fewer, those few successes could prove as far reaching as, say, discovering bacteria, or elucidating the structure of DNA.

Pursuing such a bold investment strategy for science requires an instrument unencumbered by past philosophies or conventional bureaucratic constraints. It requires fresh vision. We have worked diligently to create an effective instrument for nurturing those profound scientific breakthroughs. We need them now — for with each passing day, humanity’s problems grow ever more urgent.

The Institute has been created to incubate and nurture venture science in order to foster the kind of scientific innovation that shows potential for leading to scientific breakthroughs, or even scientific revolution. Although neither of these end goals can ever be guaranteed, the odds of meeting them can be substantially improved by following a set of operative principles that depart from the norm, as described here. These are the core principles of IVS operation.

1. The Institute will nurture challenge.

Resistance to change is natural. This is especially true for fundamental scientific change among scientists who have long dwelled in their fields. Ideas that challenge their perceived truths and associated professional standings may be dismissed or ignored, irrespective of actual merit. Proposals for change are resisted most strongly if the challenge is deemed serious. But the challenge may not succeed without getting the attention of the very scientists most attached to the issue under challenge. Therefore, the Institute will seek to bring the challenger and defender of a prevailing paradigm together to present their cases for and against the basis for the challenge. In this way, the Institute will nurture the challenge.

 

2. The Institute will avoid the temptation to specify research directions.

Breakthroughs cannot be legislated. Everyone wants a cure for cancer, a new source of green energy, and a cleaner environment. The temptation is to channel resources into those important areas. Julius Comroe’s now-classic book, Retrospectroscope, provides evidence that channeling does not work: he outlines the most significant breakthroughs in cardiovascular disease treatment and shows that all of them came from primary discoveries unrelated to the cardiovascular system. Thus, a legislated focus on clean energy will not necessarily bring the new scientific principles that lead to game-changing technologies. Relevant ideas may come from unpredictable sources. The laser came from the chance discovery of photon coherence; the transistor came from an unexpected feature of crystalline impurities. Hence, an essential principle for encouraging breakthrough science is to avoid any kind of top-down management of scientific direction.

 

3. The Institute will set up a peer-review system modeled after the court system.

Person A accuses company B of careless manufacturing practices that resulted in the death of a family member. The matter goes to court. The judge marches up to the podium, turns around to reveal his face… and who is he? He is vice-president of said company. This scenario, which the court system rightly seeks to avoid, is embarrassingly close to the operative mode of the current peer-review system. Subject experts, typically the field’s leaders, are recruited to judge their challengers. If the challenge succeeds, then those standing to lose most are the reviewers themselves. The outcome from this real-world conflict-of–interest scenario is as predictable as that from the hypothetical court scenario. Standard peer review may work well for incremental science; but for paradigm-shifting proposals it is the antithesis of what is needed for achieving the best result. Therefore, fair review requires reviewers who have nothing to gain or lose from the verdict.

 

4. Distractions will be minimized.

Envision Einstein, scratching his head at the patent office in Zurich as he daydreamed about subjects arcane such as relativity, Brownian motion, and the photoelectric effect. Einstein had time to think. In stark contrast, when a random selection of scientists working today are asked how much thinking time is available, responses range between “zero” and “very little.” There is no need to belabor the obligations that now inundate scientists, ranging from the drafting of multiple research-grant applications, to endless administrative reporting, to the preparation of an obligatory number of research papers (that few scientists will ever have time to read). Although breakthroughs may start by tripping over the unexpected, figuring out consequences that may follow from the unexpected cannot be done without uninterrupted thinking, and this requires time without distractions. Therefore, any system promoting scientific discovery must act to reduce the amount of time scientists are obliged to spend on extraneous distractions.

 

5. Investigator security will be addressed.

Stumbling on the unexpected poses a problem for today’s scientists. While dogged pursuit may bring fresh and even revolutionary understanding, deviating too far from the straight and narrow pathway carries the risk of jeopardizing research fundability; deviation therefore flirts with professional suicide. This insecurity-based fear of deviating from convention is therefore a powerful inhibitor of discovery. In an effective system for promoting scientific discovery, the investigator must have the freedom to pursue any interesting clues. Thus, any system expecting to foster breakthrough discoveries must provide the necessary freedom for scientists to deviate from the norm.

The IVS will base its operations on the principles outlined in Section 4 above. It will:

• launch promising, potentially revolutionary, schools of thought into competition with respective prevailing schools of thought
• avoid the temptation to manage science from top down, leaving investigators to determine what pursuits might be most significant
• select reviewers who have no obvious conflict of interest
• reduce unnecessary administrative burdens on investigators in order to preserve thinking time
• address issues that ordinarily inhibit investigators from entering controversial domains

These principles are taken as a constitutional foundation upon which the Institute operates.

Based on these principles, the working structure will drive toward a single goal: propelling the strongest transformative ideas into mainstream consideration, where they can be debated against the prevailing schools of thought. Competition will sharpen both points of view, setting the stage for the one that prevails. If the winning school of thought happens to be that of the challenger, then a field could be promptly turned upside down.

An effective way of launching promising alternatives into consideration is to offer them substantial support. For example, suppose the proponent of an alternative view of cancer etiology can show broad consistency with a substantial body of evidence; and suppose this approach has garnered at least a modest scientific following. One way of bootstrapping any such alternative approach is to open it to broader experimental investigation. Simultaneous pursuit of the same idea by multiple groups cannot be dismissed with a wave of a hand. The investment in the alternative line of thinking amounts to a bet that the alternative has a reasonable chance of prevailing. Supporting that bet with sufficient resources gives it a fighting chance.

Evaluation of these challenge proposals involves debates in which proponents of alternative schools of thought argue their cases against the respective orthodoxies. These debates can be carried out in writing and perhaps also orally — all posted on the web for interested parties to witness and perhaps also to comment. A panel of scientists judges the outcome. Panel members are close enough to the field to be able to evaluate the material, yet removed enough to avoid conflict of interest. Those challenge paradigms judged to be the most plausible and most potentially far-reaching are selected competitively for funding. This review procedure serves not only as quality assurance, but also as a defense against potential critics, assuring them that those chosen ideas have been carefully and thoroughly vetted.

Funding should be enough for, say, up to a dozen groups to carry forth on the same theme. Duration will need to be sufficient for building traction; yet it should be short enough to avert wasteful spending. Most critical is the multiplicity of efforts, for only if the mass exceeds critical will the challenge be impossible to ignore.

With such a funding program in place, promising challenge paradigms should quickly rise to competitive status (a process begun with the initial web debate). The sizeable body of scientists reporting on the challenge paradigm are difficult to ignore. Conference atmospheres will be immediately enlivened. Argued in a civilized manner, each paradigm’s strengths and weaknesses will soon become obvious, and the superior one should quickly emerge as the winner — potentially, a realized revolution. Instead of hanging on the vine to wither, the low-hanging fruit will have been expediently harvested.

The working structure of the IVS consists of an Executive Director, who reports to a Board of Directors. Beneath the Executive Director are a series of Associate Directors, each responsible for a particular aspect of the operation. Each Associate Director hires staff to assist with operations.

The Board of Directors periodically reviews operations and makes recommendations to the Executive Director for implementation. In developing those recommendations, the Board solicits advice from the Advisory Panel, comprising distinguished figures from science, industry and government, chosen for their experience and vision.

Future Board members will be appointed in consultation with the major donors. Ideally, the Board will comprise a mixture of seasoned, respected individuals from science and industry, all of whom recognize the value of operating on the fundamental operative principles (Section 4). Rotations may occur after overlapping periods to assure continuity. New members will be selected with input from all grantees, who should be in good positions to judge which candidates might be most committed to the principles espoused herein.

Details of the administrative operations are elaborated next, and schematized in the figure.

 

Invitations to submit proposals: Administrators broadly advertise the program, casting the net as widely as possible. Announcements contain unambiguous guidelines as to what kinds of applications are welcomed and what kinds are not. Applications must address big issues.

 

Pre-proposals: Required pre-proposals narrow the field. They discourage full proposals that fail to address major fundamental issues in science. At the same time, they provide feedback, which can help promote a shift of the scientific culture to one that becomes receptive to, rather than suspicious of, unconventional approaches.

 

Proposals: A proposal must detail the problems with the prevailing school of thought and present an alternative; it must offer detailed evidence and/or reasons why this alternative might be superior. The proposal must also include a brief outline of how to proceed initially as well as a rough budget needed to carry out that work. The material must be presented in a way that is understandable to non-experts. A limited number of letters from scientists in support of the proposed idea also could be included with the proposal.

 

Initial Screening: Proposals will first be screened for potential significance. A panel of three reviewers from outside the applicant’s field, reviewing independently, will assume responsibility for this initial gate-keeping function. Applications dealing with issues of very narrow significance, or of obvious flakiness, will be declined. Split votes warrant discussion and re-voting; a majority vote will prevail. Written comments from the panel of reviewers will be provided to the applicant. Applicants receiving a negative decision may provide written challenge. In this case, a panel of out-of-the-field scientists chosen from the reviewer pool will reconsider the gate-keeping decision and decide one way or the other, with no further recourse for the applicant. Admitted applications will move to the review stage.

 

Reviewer Pool: Since the IVS review principles differ from those of ordinary research-grant-application reviews, special care is exercised in choosing reviewers. Experienced “generalists” are desirable, particularly those who command the respect of the scientific community. An important qualification is willingness to entertain promising ideas that may seem radical. Well-suited reviewers may be those who, themselves, have posed major challenges to prevailing paradigms, for they likely understand the obstacles faced by challengers, and may therefore be especially able to judge the merit of challenges in other fields. Recent retirees may be especially suitable. The Institute can capitalize on their long experience, perspective, and mature judgment.

A pool of qualified reviewers currently exists. The list can be amended and vetted through an evaluation process set up to assure that reviewer candidates have the proper qualifications and outlook. Cronyism should not be a serious concern because the proposals to be evaluated will generally lie outside the reviewer’s immediate field. Hence, nominating a friend to assure favorable future consideration should prove ineffective.

 

Reviewer Recruitment Incentives:  Quality reviewers are not easy to recruit; everyone is busy. Yet, having reviewers with suitable outlook, experience, and devotion can make or break the program. Since reviewing can require substantial commitments of time, incentives have been put in place. One simple incentive for future consideration is to shape the position into a special honor. Another incentive, used to date, offers compensation. Meaningful compensation puts pressure on the reviewer to invest seriously in the review rather than considering it yet another burden on a busy agenda.

 

Proposal Review: A panel of five to seven open-minded scientists (to date, fewer) hears the challenger and defender in an impartial setting. The first phase of the debate is written. The panel receives the proposer’s arguments and evidence and invites written responses from the field’s leading defendants. (Defendants’ responses may be signed; this promotes responsibility, and lends confirmation of his or her leadership position in the field — an incentive for their participation.) The proposer then responds in writing to those skeptics. This written debate is made available on the internet for interested members of the community to digest and consider.

In examining both sets of arguments, panel members may have questions. They could concern the applicant’s proposal and/or the defenders’ comments. Any questions that arise will be promptly communicated and promptly answered — either in writing or through video conference — the answers made available to all relevant parties and posted on the Internet. This process should quickly clear up questions whose answers might make a major difference in the evaluation.

The panel may then move to evaluation; or, if it feels the need for amplification, it may request oral debate, either as a forum or by video conferencing. Again, such debate should be made available to the public on the Internet, drawing attention to the challenge. Indeed, the vetting process itself may be considered the first stage of public alert to the possibility of meaningful challenge to the status quo. Fierce community debate would be a sure sign of progress, for, as Claude Bernard put it, “Controversy is the lifeblood of science.”

 

Decisions: The challenge paradigm need not be proven better than the prevailing one, only to be of reasonably high potential to be proved better. Hence, the panel’s decision should not be taken by the public as an on-high pronouncement on which of two competing schools of thought is correct — a scenario that carries the danger of inciting backlash. The decision to fund is merely an evaluation of potential. Each panel member will award two scores, with higher numbers indicating higher quality: 1 – 10 for potential impact and 1 – 10 for the strength of evidence, and hence the likelihood of success. The two scores will be multiplied to obtain the total score, which will range from 1 to 100. Reviewer scores will then be averaged over the panel. A single outlier might invite additional panel discussion and possible re-scoring. In order, to diminish the possibility that a single biased reviewer could tilt the result unfairly, any reviewer’s total that remains more than one standard deviation from the mean will be removed from consideration, and the remaining scores will be averaged to obtain the final panel score.

All applications are scored in this manner.  Funding generally begins with the highest score and continues until available funds are exhausted, although the Board reserves the right to make final decisions.

 

Funding amounts and durations: To ensure that a critical mass of supporting results can be accrued, each selected theme must come with a commitment to fund multiple research teams; otherwise, the idea is unlikely to take hold no matter how promising it might be. The review panel might suggest the appropriate funding level for the applicant, as well as for the overall effort. As a rough guideline, some ten to 12 standard-size grants would be reasonable. For example, funding of a dozen groups at, say, $500K direct costs per year per group would amount to $6M; with overhead included, the level could rise to, say, $8 -10M. Smaller amounts should suffice for theoretically oriented research, such as mathematics and theoretical physics – with grand totals amounting to perhaps only $1 – $3M. Larger amounts might be needed for projects requiring expensive investments such as super-colliders or ventures into space. Special consideration is given to the applicant, who is, after all, the main driving force.

As for duration, a reasonable minimum would be five years, similar to MacArthur Fellowships and Royal Society Fellowships. Five years should be long enough to determine whether the challenge is making headway. The five-year grant comes with the understanding that success in gaining substantial influence on the field would significantly enhance a project’s likelihood of receiving follow-on funding, to continue any necessary buildup of momentum. Advance knowledge of this opportunity for follow-on funding should help entice otherwise reluctant investigators to enter into the high-risk arena with the understanding that the funding period can be extended by substantial progress. The merit for this extended-period funding will be evaluated similarly to that for the initial-period, except the technical portion of the application must contain a report of progress. Evaluation is not based solely on the number of publications and/or journal-impact factors because these are not necessarily measures of influence; rather, it is based primarily on more direct signs of increasing influence on the field, which may be best judged mainly by interviews with the fields’ scientists, though increasing citations in the field will not be ignored.

 

Selection of participating investigators: The investigator responsible for the grant, hereafter referred to the “lead investigator” or LI, is one of the multiple participating investigators. As the main driving force, he/she may help select the other investigators to participate. It is important to guard against applicants feigning interest in the challenge merely to obtain funding. A good judge of this issue is the LI, who may have first-hand knowledge of scientists who genuinely value the proposed approach, and who has much to gain by identifying those who are genuinely interested.

Nevertheless, some checks and balances are necessary to avert cronyism, or even the appearance of cronyism. A reasonable approach is for the lead investigator to nominate other participants. Each nominated participant will draft a five-page outline of his or her proposed plan, along with a budget and justification. An IVS-assigned program manager for the collection of teams and the LI reads these applications and discusses their strengths and weaknesses. The IVS administrator then decides on funding, with the advice and consent of the LI. If the number of participating groups is too small, then additional five-page applications will be solicited. These will undergo similar vetting. The topic will generally be kept open for substantial periods until the budget allocation has been exhausted, the expectation being that promising initial results and public discussion will inevitably attract additional qualified investigators.

 

Coordination, Reporting, etc.: The burden of reporting must be kept to a minimum to preserve the investigators’ time for thinking. On the other hand, periodic checks for progress are necessary, and should these checks reveal that the money awarded to any one group is not being spent effectively, or should the research direction shift thematically, the administrator will have the capacity to terminate funding and direct it instead to another group. Such action will follow a probationary notice, with final action taken by a high-level board. It is understood that a result that disagrees with the proposed idea is not a reasonable basis for discontinuation as long as it provides additional insight

For maximizing visibility, coordination among participating groups is important, and it is the LI and the program manager’s responsibility to coordinate this effort. Meetings twice per year could be effective vehicles for sharing data, and discussing future strategies.

With the critical mass of activity achieved through this program, challenge ideas with real potential are expected to quickly rise to the status of competitive paradigms. Challenge and prevailing paradigms then become rivals, vigorously debated at meetings and argued in the literature. Such debate will inevitably sharpen both sides’ arguments, building inexorably toward a winner. In this way, the IVS process should considerably accelerate scientific progress with significant breakthroughs leading in some cases to major paradigm shifts.

A Board of Directors guides the Institute and ensures that administrators adhere to the foundational principles outlined herein. A relatively small Board, say up to five or seven members, ensures that the group is in fact a working group rather than a figurehead group. Candidates for the Board should present evidence of their commitment to the principles espoused here, as well as a commitment to expend the time required to keep the Institute properly functional.

An Advisory Panel helps guide the Board of Directors. It meets periodically to consider pending IVS issues, and otherwise advise the Board on matters of policy and operation. The Panel will be augmented and revised periodically by the Board.

The Executive Director is the Institute’s chief administrator. Appointed by the Board, the Director assumes responsibility for day-to-day activities of the Institute, including the hiring of senior personnel. He or she reports to the Board. Like Board members, the Director should be a person with demonstrated commitment to the principles espoused herein as well as demonstrated evidence of administrative capability.

Associate Directors take responsibility for various phases of the operation, and report to the Executive Director.   Associate Directors could, for example, take responsibility for proposal review, fiscal matters, communications, legal issues, etc.

Program Managers take responsibility for administering funded grants. They need not be scientists but should at least be science-savvy, and should be chosen based on their openness to fresh ideas and their managerial competence. Program managers report to an Associate Director. Each one might manage one or more multi-group grants. Their role is not only to administer funds, but also to assist investigators in dissemination and coordination, with the understanding that their primary goal is to help expose the new school of thought to the mainstream scientific community as effectively as possible.

Program Managers will ultimately be judged by the success of the grants they administer, i.e., by the fraction of those grants that have sparked revolutionary change. Hence, they should be naturally incented to work cooperatively with the participating investigators, who have much the same goal. This commonality of purpose should help forge a properly symbiotic and effective working relationship.

Staff will be needed to support the activities of the people above.

Ultimately, the number of personnel required at full operational activity is estimated to be several hundred (fewer per grant dollar than government granting agencies).

The steady-state budget is considered first, after which the budget for the ramp-up period is considered.

A. Steady-State Budget

For projecting an appropriate annual budget to fund research that challenges the status quo, a possible guideline is to establish a meaningful fraction of the budget for more traditional research. One percent seems a realistic minimum. The annual budgets of NSF and NIH total on the order of $40B. Adding the annual budgets of EU, Asia, and other countries brings the worldwide total to probably about $100B. If defense agencies are included, the figure will be higher. Hence, a 1% guideline implies an IVS annual budget of $1B.

An alternative guideline starts with an estimate of the number of thematic challenges that might merit funding. Any such estimate may be suspect, however, because no relevant data exist. Even in their own fields scientists are sometimes unaware of meaningful challenges — the reason being that the fields’ leaders have little motivation to advertise them. Thus, challenges are usually well-kept secrets. Working scientists harboring their own challenges to the status quo will often “come out of the closet” only after retirement because of the present threatening climate.

Nevertheless, some estimate is possible. The initial round of IVS pre-proposals revealed several dozen serious challenges to convention. These challenges must represent a fraction of those throughout science’s many diverse fields, for the call for pre-proposals reached only a limited number of scientists.  Thus, a reasonable estimate of the number of meaningful challenges may be on the order of several hundred. Funding 100 themes in the steady state would require an annual budget of $1B ($1M per research team times 10 teams per theme times 100 themes).

From these two sets of considerations, a steady-state annual budget on the order of $1B seems a reasonable target.

The budget must include administrative costs, which should be relatively modest fraction of the amounts awarded. A rough estimate of steady-state running costs, including facilities, personnel, equipment and supplies is 3 to 5% of the grant budget. NSF administrative costs, by comparison, run at 5%.

This budget will be funded by interest earned from a permanent endowment. The total annual amount drawn for spending on grants and administration should ensure no diminution of the principal, so that the IVS can continue in perpetuity. Hence, the amount spent may vary somewhat from year to year. 

B. Ramp-up Period

Currently in its foundational period, the IVS is now entering the period of resource buildup.

The duration of this ramp-up period will depend on the amount of money available to spend during this period. It is understood that the principal will build in stages, and that early on, some of the accruing principal will need to be used to fund projects and operations. Here we provide an illustrative example of five-year ramp-up plan, understanding that the plan is merely illustrative. 

• Year 01
  Initial quarter: hiring personnel, setting up physical facilities, refining strategies for disseminating grant opportunities and for reviewing. Second quarter: advertising opportunities broadly, hiring additional staff, preparing for round of reviews. Third and fourth quarters: receiving and reviewing proposals, with the goal of funding 40 themes before the end of the year. Estimated cost for one quarter’s funding of (40 themes) x ($10M/year/theme) = $100M. Thus, a projected budget, including administrative costs, just over $100M.
• Year 02
  Continue funding of first 40 grants, as well as review and funding of 30 additional proposals over the course of the year. Thus, 40 grants funded for a full year ($400M), plus 30 funded for, say, on average, one-half year ($150M), plus modest administrative costs,  totals slightly more than $600M.
• Year 03
  Continue funding 70 themes ($700M), and add half-year cost of another 10 themes ($50M) plus modest administrative costs, totaling approximately  $800M.
• Year 04
  Add half-year cost of another 10 themes, yielding a total of a little under $900M.
• Year 05
  Add half-year cost of another 10 themes, yielding a little under $1B. This is close to the steady-state budget, which, covering 100 full-year grants at $10M, plus 5% admin, totals $1.05B.
• Additional years
  Replace expired grants with a combination of renewals and new grants.

Maintain budget of approximately $1B, and perhaps seek additional investments if the Foundation’s program is shown to be particularly effective. 

For a substantial investment of this nature, program evaluation is obligatory.  The criterion for success is simple: how many meaningful breakthroughs or scientific revolutions has the program spawned? This should be the sole criterion for success, and if the answer is few or zero, then the program should be seriously revamped. Nevertheless, as the only experiment of its kind, breadth, and magnitude in the history of science, it can be expected that something profound about human nature and/or science would be learned from failure.

How can one determine the number of scientific breakthroughs and even revolutions? Certainly, this cannot be done by the usual standards of counting peer-reviewed published research papers. A more effective approach is to compare the prevailing paradigm at the time of initiation of funding with the prevailing paradigm at the time of evaluation, thereby determining the extent of shift. This could be done through examination of the literature and through interviews with members of the relevant scientific community. In some cases, the shift should be obvious by inspection — the discoveries of prions and ulcer-causing bacteria H. pylori, for example.

At what stage should the evaluation be conducted? Considering the duration of the ramp-up period, and the time required for revolutions to unfold, a reasonable time might be five to ten years following the onset of thematic funding. By that time many of the projects will have matured, and ample time will have elapsed for determining whether the program has succeeded. At that point, decisions could be made about the need for and nature of changes in the Institute’s approach to accelerating the advance of science.

Three endeavors should be considered in the future to help foster the Institute’s progress toward its goals: (i) an educational component; (ii) an in-house research component; and (iii) a parallel entity to support development of technologies emerging from these discoveries.

(i) Today’s high school and college systems teach students to accept textbook material as ground truth. Building on those ground truths, graduates go on to solve scientific problems. If those “ground truths” are valid, then their solutions may be correct; if they are not valid, then the “solutions” may mislead — as demonstrated in the pre-Galileo era. The IVS is based on the presumption that many “generally accepted” truths are not necessarily valid. The IVS promotes the pursuit of new truths. Hence, the all-accepting, acquiescent, culture emerging from the current educational system is at odds with the questioning culture the Institute aims to foster.

The IVS proposes that an appropriately designed alternative college-education model can provide the basis needed to more effectively train future scientists:

• The IVS Academy will focus on applicants who have demonstrated motivation for, and sincere interest in, science. Achievement in science is not a prerequisite.
• It will educate those students broadly. Current educational programs at the university level create narrow super-specialists. Those individuals are poorly equipped to solve most problems: unless the solution to a problem happens to lie within one’s narrow window of expertise, the best solution might be missed. Broad education grounds students in diverse disciplines including the creative disciplines, equipping them to look broadly for the optimal solutions.
• The IVS system educates students to question assumptions. A proposed student exercise will teach students to objectively evaluate even broadly accepted scientific principles. For example, the student may choose Bernoulli’s principle. He/she will trace the origin and rationale for this principle, review all objections (dissenters exist for almost all scientific principles), evaluate the worth of those objections, and draw conclusions as to the level of confidence we can have in the principle’s validity. Performing this exercise for several foundational principles will teach the student that not all principles can be automatically accepted as ground truth; their domains of validity need proper evaluation.

Educating motivated students to be broad and inquisitive will prepare graduates for careers that fit squarely within the IVS framework. Graduates will be equipped to tackle the most challenging problems of science. This educational program might begin modestly and evolve over time, perhaps into a university or an international academy of scientific scholarship. Its operating principles could constitute a badly needed model for other universities to follow: current educational systems are under attack; the proposed system might serve as a creative response. Some change is evidently needed, and the IVS educational model could serve as the focal point for that change.

(ii) A second initiative is an in-house research unit. Current research institutions and institutes are ill equipped to accommodate scientists pursuing unconventional approaches. Those scientists are often treated as pariahs, shunned by traditional scientists and sometimes forcibly ejected from their ranks. An example is the late Halton Arp, a controversial astrophysicist trained at Harvard and Cal Tech, whose questioning of the “Big Bang” theory terminated his access to the telescope he had been using, forcing a move abroad to continue his research. Another example is Ignaz Semmelweis, an aspiring young Hungarian physician in the pre-antibiotic era, who found that the simple act of handwashing before conducting internal examinations in the obstetric ward could save many lives. Semmelweis offended his colleagues, lost his position, and finally died in an insane asylum. Yet another example is Jacques Benveniste. Once a respected French immunologist, Benveniste became the target of worldwide ridicule when he found evidence that water could store information. Though he lost his laboratory, multiple groups have confirmed his results.

An in-house laboratory could constitute a think tank, where scientists cross-fertilize each other’s ideas and pursue what they think important. It could serve as a suitable place for graduates of the training program (subsection i, above) to pursue their creative ideas. The laboratory might function as did the legendary Bell Telephone Laboratories, where gifted scientists and engineers working in an open atmosphere succeeded in creating scientific breakthroughs that spawned earth-shaking inventions, ranging from the transistor to the laser. The in-house laboratory could function similarly.

(iii) A third initiative would garner support for emerging new technologies. The transformative research supported by the IVS intends to produce breakthroughs in fundamental science. Many of those scientific breakthroughs will spawn ideas for technological advances spread over a wide industrial base. Developing those technologies will need support. While venture capitalists typically prefer investments likely to produce short-term gains, product ideas coming from revolutionary science may be riskier and may therefore require longer-term investments that venture capitalists are reluctant to pursue. We envision a vehicle for funding those long-term investments: the “Institute for Venture Technologies,” or IVT.

Distinct from the IVS, the IVT could be a for-profit institution. Investors could donate funds to set up the IVT in much the same way as they donate to the IVS. In the IVT, however, investors may eventually profit from the success of the funded ventures in the same way that venture capitalists may profit.

In this way, the IVT can be the natural complement to the IVS — the scientific investment’s practical fulfillment and realization. The two Institutes could be loosely linked, but administrative separation is critical in order to avoid the potential for the IVS to make funding decisions based on eventual profit potential. Any such prospect could compromise the very purpose of the IVS.

On the other hand, technological innovations spawned by the IVT could prove the IVS’s ultimate worth to the world. Those innovations could have impact on everyone. It goes without saying that the expected outpouring of new technology from the IVT could invigorate the world’s economic engine, and help solve humanity’s ever-increasing problems.

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Setting up these three additional programs will be major endeavors, best attempted after the IVS has matured and energies can be properly directed toward new endeavors. Waiting several years before considering the pursuit of these initiatives seems prudent.

Inevitably, the IVS operational plan will have shortcomings. We have considered some potential issues that may arise, and the solutions we envision to address them.

Resistance from well-funded scientists.

The Institute is not meant to replace current research-funding systems, but to complement them. Existing agencies worldwide are effective in funding incremental science, which is essential for progress. Some of those agencies wrestle with the funding of transformative science, and if those programs are effective, then many new revolutionary ideas may begin to launch. Those that mature successfully will be poised for the multiple-group support that is the heart of the IVS. Thus, the Institute might be viewed as a second-stage investment — more complementary than competitive.

Seen as funding crackpot ideas.

Grants awarded for pursuing topics that challenge current wisdom will inevitably arouse public suspicion. It has happened before. Any high-risk program cannot help but fund some topics that may seem by current standards as too far “out of the box.” Those most vulnerable to attack can sometimes be the ones that carry the highest potential.

The key counter-argument is that a system of checks and balances restricts the number of crank ideas that make it through the initial screening. All proposals are as vetted as thoroughly as reasonably possible, first by scientist-administrators and then by a review system that mimics the jury system. It guarantees that the opposition will be adequately heard, and then puts judgment exclusively in the hands of qualified third parties who have no stake in the outcome. Crackpot ideas should rarely if ever make it through the door.

Seen as too narrow. Why not diversify the types of programs offered?

Many other program types could be considered; for example, providing small grants for speculative ideas, and assisting young people with innovative ideas to gain career footholds. However, such programs lie more naturally within the purview of existing granting agencies, and the IVS should not compete.

Of the possible programs those agencies could offer, a sorely needed one would seed young people with transformative ideas into junior faculty positions. Such aspirants are now routinely passed over because they are deemed too risky to ensure future funding. To solve this problem, the Royal Society has developed their 5 + 5 year fellowships, which transition into tenured faculty positions. A program modeled after this one might invite transformative proposals from people at the postdoctoral level. Those selected would be given a letter of assurance that if they can secure a tenure-track position at a research university, their research group’s full running costs including salaries and overhead would be covered for a duration of 5 + 5 years. Provided they win tenure, the respective university would in turn agree to take over their support at the termination of the grant period. Programs of this sort have worked successfully in the UK and Europe, and could jump-start creative young scientists who wish to pursue approaches that diverge from the mainstream.

Current granting agencies might consider establishing such programs. If there is no interest shown, then the IVS could consider developing them in the future as supplementary to its main venture program. At present, it seems prudent to remain sharply focused.

Won’t the Institute inevitably fall to the whims of special interests, which would divert the system to their desired ends?

Achieving continuing success in any program is a delicate matter, requiring careful vetting of those chosen to guide and direct the Institute. If sufficient attention is paid to the selection of these people, then the Institute should remain robust and relatively immune to those who would distort its intent for their own advantage.

The most critical choice is that of Board members, for they oversee the entire operation, including the selection of the Executive Director. To guard against domination by special interests, the IVS design calls for input from the stakeholders themselves. Thus, funded recipients will have some say in the people they feel will be most suitable in guiding the Institute according to its foundational principles. With input from those recipients, the major donors, with advice and consent of Board members, will make the final decision. This mechanism offers at least some immunity from distortion by special interests, which is a realistic concern.

Will the program really facilitate revolutionary breakthroughs?

Essentially, the program design nurtures revolution. The approach invests in serious challenges to the status quo and elevates the most substantive ones into competition with traditional views — a short step from community acceptance.

The review process, itself, also nurtures revolution. This happens in two ways: First, the open review format virtually guarantees that challenge paradigms will be widely discussed, even among the public; as a result, fields now moribund should soon come alive. The very act of being considered elevates the challenge paradigm into competitive status. Second, the review process facilitates the sorely needed transformation, from a culture that reflexively dismisses challenges as the whims of misguided cranks, to a culture that is more open to fresh thinking, even radically fresh thinking when data and logic compel. It restores the respectability of paradigm-challenging approaches, which should, after all, be the mainstay of science. Such cultural change will not in itself guarantee breakthroughs, but it cannot help but facilitate their emergence.

Taken together, these factors lend optimism that revolutionary breakthroughs will emerge, perhaps in significant numbers, and perhaps soon.

Can non-experts adequately judge the sometimes-arcane scientific arguments? Won’t they be deluded into funding off-the-wall ideas that have little chance of success?

In this era of complicated science, it is often held that only the field’s experts can judge the merit of proposals lying within their field. This is certainly true in some cases; in sophisticated technical matters particularly, non-experts have no way of judging a priori who might be right. This is the very reason why we invite the fields’ recognized experts to argue their defense in front of the panel. The debate should help make clear whether the defense is meaningful.

On the other hand, for fundamental scientific issues that are clearly thought out, non-experts should be perfectly capable of understanding. As Lord Rutherford once said, “If you really understand something, you can explain it to your grandmother.” The burden of communication is thereby placed on the proposer, who will be successful only if the arguments are presented clearly and logically. Although chosen panelists will be far enough removed from the field to avoid conflict of interest, they will be close enough to appreciate arguments that are cogently presented. Indeed, the MacArthur Foundation sometimes employs artists to judge scientists, and the system seems to work just fine.

Can a dozen groups that agree on the challenge of a field’s status quo be found?

If fewer groups are found, then fewer grants will be funded, and the unspent money can be used elsewhere. However, this scenario seems unlikely. Those who challenge are invariably in contact with others who support their challenge, and those supporters would require scant enticement to participate. The web-based debate will attract others; presentations at meetings still others; and additional participants will come from the Institute’s broad solicitation. A more likely problem is not too few but too many groups: deciding which of the many applicants are the most qualified may be more challenging than attracting enough applicants.

Won’t establishment defenders be difficult to recruit?

Experience to date shows moderate difficulty, with ultimate success. Defenders of orthodoxy often reflexively dismiss the challenger’s view. Here, such a dismissive approach will not succeed, for there is turf to protect. By declining any meaningful defense, the defender facilitates the uncontested awarding of handsome funding directed against the very foundation on which the defender’s career is based. This threat should constitute a loud wakeup call. A further point is that the defender may be flattered by being chosen as a scientific leader, certifying his or her position in the field. A final carrot is a meaningful honorarium offered in compensation for the goodly amount of time required to prepare a proper defense.

Isn’t this program awfully profligate in this period of economic uncertainty?

If bold science is to be fostered, then the mechanism itself needs to be equally bold. What’s at stake is the very future of the world, for a world without scientific leaps is a stagnant world, susceptible to decline.

In terms of return on investment, this program shows extraordinary promise. Scientific breakthroughs almost always generate new technologies, whose economic potential can be remarkable. Think of the laser, the X-ray machine, the television, the Internet, the wonder drug, the Xerox machine, etc.  These technological breakthroughs were unanticipated sequels to scientific breakthroughs, all made decades prior. The worldwide market for new technologies is practically limitless, and hence the return on investment in this program is likely to be extremely high.