Scientific Processes
Scientific Processes at Human Scale
The Scientific Processes section highlights cultural issues involved in the practice of science and offers a couple of recommendations for the future. The goal is to assess how the structures that support basic science activities and translational research efforts can be improved. The text below draws heavily on and includes excerpts from two freely available articles published by the Institute:
Translational Research: From Biological Discovery to Public Benefit (or Not) (2014)
Percubator Concept (Academic Percolation <---> Business Incubation)
A percubator is an environment where academic percolation and business incubation occur together, back and forth, short-term and long-term, without artificial walls of separation, and where investigators are enabled to use their knowledge to rapidly move their discoveries to the public. A percubator is a partnership between academia and business that incorporates the best of both to responsibly but urgently translate research findings into useful interventions.
Importantly, the program corrects a fundamental engineering problem present in most translational research systems - inefficient bi-directional movement of individual researchers between academic and commercial silos.
Some might argue a percubator blurs an important distinction between basic science and private sector activities, but this is not accurate. Academia is a scintillating environment where investigators can ponder and question nature irrespective of an immediate utility - it’s a percolator of ideas, inventions and biological discoveries, a place where one can ‘wonder if and wonder how’. In contrast, companies focus primarily on applied science, taking early concepts from the percolation phase and incubating them through early testing, and then into the competitive world of the marketplace and clinic.
The goal of a percubator is not to meld these two modes of thinking together; rather, it is to remove the barrier that separates them and allow free and unfettered movement of investigators between the two, anticipating that it will be synergistic to do so and even necessary in some instances, especially considering the arduous path from laboratory to the public.
Development of a drug or medical device is not a linear and unidirectional movement of a single idea, but is an iterative and parallel movement of many related sub-ideas and sub-projects occurring at various points and in different directions along the translational vector. Repetitive cycles must be performed; from percolator to incubator and then back to the drawing board (percolator) again to solve this problem or that. A translational system of ‘academia discovers over here and then biotech or pharma commercializes over there’ is not ideal. A percubator will allow these activities to occur in one place, under the long-term and sustained direction of one individual, and will augment the methods that are currently in place.
A percubator program offers two important elements to facilitate translational research; direction and drive.
Direction - The primary goal of a percubator is to fully engage investigators in long-term and creative translation of their discoveries to benefit the public: “I think this application has great market potential and is ready for corporate development - that one is best developed through an L3C (low profit limited liability company) - those two are going to be important five years from now and need to percolate more – and this one is risky and has a limited market, but I am going to try to commercialize it anyway, the science is interesting and it could help patients.”
Drive - Once direction is established the success of a translational endeavor then shifts to the motivation of the participants involved. Pride of inventorship, a desire to make scientific progress and to be recognized for doing so, and a longing to help patients are strong motivations in themselves, but are not always sufficient for this arduous undertaking. A percubator also harnesses the clarion call to the entrepreneur, one of the most potent forces of the human psyche. To many of them the ‘fire in the belly’ is the creation of new commercial life; seeing, believing in, and growing an entity that meets a need, with the freedom to pursue unique directions and the operational control to turn-on-a-dime as conditions warrant in order to make progress. The process is thrilling, motivating and difficult all in one, much like parenting a young child and nurturing them along. To disregard or diminish this particularly important element within a translational system is imprudent - we do so at the peril of the public we seek to help.
A primary problem in today’s system is not that there are too many entrepreneurs involved, but that there are too few. Most universities, government science agencies, and private sector companies are chock-full of invention reports and patent applications generated by employees, 99% of which will never be brought to the public or patients owing in part to the ‘discover in this silo but commercialize in that one’ mentality that rules the biomedical research enterprise.
Moreover, it is typically only the 1% of inventions with the most obvious short-term commercial value that are picked up by companies or investors, since a path to profitability is clear and likely. The other 99% of inventions are neglected and die on the vine. But the history of science and medicine are replete with examples of critical advancements that ‘everyone (industry, investors) knew would never work,’ but which then did work and generated great value for the public and patients.
The other 99% is where a percubator can play a critical role as the discovers and creators, bursting with inventors’ pride and in an environment that supports binocular academic-industry endeavors, can percolate and incubate ideas short- and long-term, sometimes publishing the findings in scientific journals and other times driving a new concept all the way to the marketplace.
Of course, a percubator needs to function in an ethically sound manner. Specifically, such programs should not involve investigators or administrators with regulatory roles or policy duties. Rather, the environment is meant to support inventors, creators, and discoverers in bringing their own efforts to the market and patients, in the bright sunshine of full disclosure of activities, and with strict ethical limits on involvement in the process once a drug or device reaches clinical testing and patients.
In summary, a percubator is a strategy to enhance translational activities that fully integrates the free thinking mentality of academia with the productive drive of the private sector in order to ensure that no stone is left unturned in efforts to help the public and patients.
Translation of Biological Research (or Not)
Advances in biology are occurring at a breathtaking pace today, from genetic insights facilitated by the Human Genome Project and next generation DNA sequencing technologies, to global nucleic acid and proteomic expression measurement using new high-throughput methods. Certainly, the basic science ecosystem is productive and this portends well for the myriad new applications that will benefit mankind; drugs, vaccines, devices, and related economic growth – or perhaps not – in stark contrast to the generation of fundamental biological knowledge are inefficiencies in applying this information to real-world problems, especially those of the clinic. While investigation hums along at light speed, translation often does not. The good news is that obstacles to progress are tractable. The challenging news, however, is that these problems are difficult.
To ensure proper communication it is necessary to agree upon definitions, especially in translational research since much of the jargon that touches upon the field is used inexactly, with varying connotations and interpretations.
As a Process – Translational research is thought of broadly as the progression of a new scientific insight or discovery into a useful product, medicine, or other societal interventions. The endeavor covers all areas of science, from biological to physical to social, and essentially any effort to create public benefit from studies utilizing the scientific method fit into this category.
As a Science – Investigations can be divided into two categories that are relevant to translational research: basic and applied science. Basic studies seek fundamental knowledge, are nondirected, and are driven by curiosity and by a desire to understand a physical or biological system. The fundamental knowledge generated is an end unto itself. In contrast, applied research is a focused and targeted effort that seeks a specific goal, a solution to a problem.
One distinct area of translational research in need of assessment is the so-called silo problem.
When one asks investigators about challenges in translating new research advances into applications, a frequent complaint is the difficulty in traversing the various components of the system; disciplines and subdisciplines in academia, the laboratory, the clinic, and the public and private sectors.
Certainly, there are many positive aspects emanating from scientific and medical subcultures; silos are not all bad. However, when the biological or clinical problem at hand requires a multidisciplinary approach or requires the synergy of more than one discipline, the translational system begins to show its weakness – instead of whirring along productively, the process becomes slow and ossified.
There is one aspect of the silo problem within academia that stands out as particularly pernicious, a concept akin to pouring molasses onto the process. Many in the research community agree the issue is especially problematic and needs to be resolved, and sooner rather than later. Others are harsher in their assessment – worst idea ever.
The concept is that an individual investigator can be either a basic scientist or an applied scientist, but never both – each person must stay in one silo or the other. An ingrained cultural academic credo accompanies this sort of thinking, often proclaimed loudly and in an authoritarian tone; “Everyone knows that basic scientists are highly superior to applied scientists since they are pure, noble, and unencumbered by the grubbiness of commercialization.”
What follows naturally is that doing applied science somehow lessens one’s ability as a basic researcher and that less knowledge and breadth of experience are preferable to more. A hyperfocus on one’s primary scientific interest within a silo is said to be the only way to succeed. Never mind that the actual evidence is contradictory to this assertion, as investigators who are the most entrepreneurial remain productive with respect to basic science, produce large numbers of high-quality scientific publications, and are often the superstars of their fields. And never mind that even the most theoretical of academic scientists and mathematicians typically participate in a wide range of activities: teaching, mentoring, fundraising, grant writing, and departmental faculty matters to name a few. Participating in applied science and commercialization at a modest level, or even as a consultant, is considered disqualifying by many, rendering one impure, on the dark side, and no longer capable of performing high-quality basic science.
To the uninitiated, the silo problem may appear as an amusing and somewhat silly aspect of human nature within the scientific community; that researchers like to encase themselves into a silo and tell everyone who will listen why their particular discipline is better than others. But to the initiated this is a grave problem. Self-imposed compartmentalization. A highly ingrained, dogmatic, and cultural ethos passed down from generation to generation – stay in your silo, all other work is inferior, and commercialization is uncouth to boot.
One outcome of this basic versus applied mentality, an insidious aspect, is that commercial and clinical applications become 'someone else’s problem.' For many academics, simply doing basic research, generating knowledge, and publishing manuscripts is sufficient. Their day is done.
But consider the effect of this scenario on the translation research process. The people who best know the intricacies of a particular line of scientific inquiry – the creators, the discoverers, and the inventors – the key holders of information, both theoretical and experiential, remain on the sidelines and do not participate significantly in moving their own discovery work to patients and the public, based on a premise that is patently untrue, that human beings cannot multitask.
From a first-principles engineering viewpoint, could there be a worse design flaw in today’s translational system? The role of the most important element, the creative individual scientist, the key driver of progress, is artificially diminished – their energy, drive, knowledge, and expertise dissipate away – and it is someone else’s problem.