The Wyss institute: A new model for medical technology innovation and translation across the academic‐industrial interface

Abstract The Wyss Institute for Biologically Inspired Engineering at Harvard University was formed based on the recognition that breakthrough discoveries cannot change the world if they never leave the laboratory. The Institute's mission is to discover the biological principles that Nature uses to build living things, and to harness these insights to create biologically inspired engineering innovations to advance human health and create a more sustainable world. Since its launch in 2009, the Institute has developed a new model for innovation, collaboration, and technology translation within academia, breaking “silos” to enable collaborations that cross institutional and disciplinary barriers. Institute faculty and staff engage in high‐risk research that leads to transformative breakthroughs. The biological principles uncovered are harnessed to develop new engineering solutions for medicine and healthcare, as well as nonmedical areas, such as energy, architecture, robotics, and manufacturing. These technologies are translated into commercial products and therapies through collaborations with clinical investigators, corporate alliances, and the formation of new start‐ups that are driven by a unique internal business development team including entrepreneurs‐in‐residence with domain‐specific expertise. Here, we describe this novel organizational model that the Institute has developed to change the paradigm of how fundamental discovery, medical technology innovation, and commercial translation are carried out at the academic‐industrial interface.

biomedical research. As a result, the boundaries between living and nonliving systems are literally breaking down.

The Wyss Institute for Biologically Inspired Engineering at Harvard
University 1 was founded in 2009 based on the belief that we have uncovered enough information about how Nature builds, controls, and manufactures from the nanoscale to the macroscale that we can now leverage these biological principles to develop new engineering innovations. We named this burgeoning field, "Biologically Inspired Engineering," to clarify how it differs from the more established disciplines of Bioengineering and Biomedical Engineering that continue to apply engineering principles to address biomedical challenges.
The Wyss Institute's mission is to discover the biological principles that Nature uses to build living things, and to harness these insights to create biologically inspired engineering innovations to advance human health and create a more sustainable world. Its foundation lies in the recognition that breakthrough discoveries cannot change the world if they never leave the laboratory. And thus, the Institute was designed to confront the challenge of translating technology advances across the academic-industrial interface, as much as it was created to catalyze the emergence of Biologically Inspired Engineering.
The Institute is similar to other academic research institutes in that it resides within the academic ecosystem of Harvard University. But the structure of the organization is specifically designed to overcome many of the challenges that in the past have held back technology innovation, intellectual property generation, and the commercialization of academic discoveries. This is crucial because these translation challenges continue to be a major stumbling block for universities and hospitals as they attempt to transition the discoveries their faculty and staff make into the marketplace where they can improve patients' lives.
In this article, we provide an overview of the organizational model we have developed to enable cross-disciplinary research collaborations, support technology innovation, augment intellectual property generation, and ensure efficient translation of discoveries into products that enter the marketplace in order to enhance human health.

| A N E W P AT H T O A CA DE M IC I N N OVA TI ON WI TH A TR A NS L A TI ON M I SSION
Companies tend to be optimized to generate intellectual property, protect its value, and develop products efficiently; however, as they are primarily focused on maximizing shareholder value, they often do not support pursuit of high-risk ideas that arise in their organizations. Difficulties in fostering innovative technology development are typically compounded in industry by most companies' unwillingness to change market direction and refocus operations due to the large capital investments they often have made for scale up and manufacturing of existing products in already well-defined market segments. In contrast, academia is a cauldron of innovation and creativity, but the focus is on publications with little focus or investment in intellectual property creation and its translation into useful products; thus, only few research advances have any direct impact on society at large.
The Wyss Institute was launched with a $125 million gift to Harvard University from Hansj€ org Wyss, which at the time was the largest single philanthropic gift in the University's history, and this was supplemented by contribution from Harvard as well. Based on our success within 5 years, our donor doubled his gift to $250 million. As a philanthropic entrepreneur who had been the CEO of a large medical device company, the donor shared this view and noted that "Big companies will not take risks. I try to convince my people to change directions, and they do not respond; it's like trying to turn a huge tanker. You academics do innovative things, but all you do is publish papers and make widgets. What I would like to see is an innovative startup in the world's greatest academic environment that will take risks and have positive near term impact on the world." As a result, the Wyss Institute has pioneered a new model that combines the focus on applications, intellectual property generation, and commercialization commonly found in a start-up with the creative freedom and flexibility of academia. The measures of success that were established when the Institute was formed included academic ones, such as international recognition for our scientific leadership, and recruitment of world-class faculty, students, and fellows. However, we are also assessed based on the patent portfolio we generate and our ability to develop productive corporate alliances, licensing agreements, and new start-ups. Having our bioinspired technologies being sold or productized to achieve near-and long-term impact is the ultimate measure of the Institute's success.
In traditional academic settings, graduate students, postdoctoral fellows, and young faculty are not commonly trained to patent the technologies they invent, and their career advancement is not linked to their success at reducing innovations to practice. This is one of the major reasons why academic research produces a huge amount of information and innovations that are potentially exciting, but they rarely leave the laboratory, resulting in little or no positive impact on our broader society. The Wyss Institute aimed from its beginning to address this gap.
Given this focus, one of our major goals was to create a rich environment that is specifically designed to support interdisciplinary research and intellectual property generation, as well as prototype development, testing and validation, thereby de-risking technologies both technically and commercially. Our belief was that in addition to generating stronger intellectual property, successful maturation and de-risking of technologies led by a multidisciplinary collaborative team of world-leading scientists and engineers would attract funding from both industry and government agencies that are focused on development of disruptive technologies (e.g., DARPA, IARPA, DoD, etc.), thereby increasing the likelihood that these innovations will transition to the marketplace. However, to accomplish this, we realized that we must build our community from the bottom-up, because all creative endeavors are based on people.
To achieve these unique goals within an academic setting, the Wyss Institute was set up to span all Harvard schools and departments, and not be confined within any one school. In fact, it became a nonprofit 501(c)3 corporation inside Harvard University with its own governance structure in 2013. The Institute's Board of Directors, which includes both Harvard and external members, is tasked with the overall governance of the Wyss Institute. Programmatic decisions are made by the Institute's Operating Committee, comprised of the faculty leads from each of the six enabling technology platforms described below, ensuring that faculty members are in control of the programmatic direction of the Institute. Through this governance structure, the Institute has been able to establish semiautonomous research and administrative operations, policies, and procedures that are both consistent with those of Harvard, while meeting the Institute's needs for flexibility and adaptability. Institute administrative staff are recruited with a strong emphasis on the fit with the Institute's entrepreneurial, collaborative, and service-oriented culture, which results in high-performing administrative teams similar to those more commonly seen in start-ups, which focus on advancing the Institute's mission by specifically meeting the needs of the Institute's faculty and researchers. Institute staff crisscross the university and partner institutions, and work collaboratively with staff at various Harvard schools to administer interschool academic appointments, manage research, ensure compliance, and oversee sponsored funds and finances. The Institute is not an academic appointing unit, so all of its faculty have academic appointments in their home institutions, and most faculty (except for new junior hires) maintain research laboratories at their home institution, while also conducting research at the Institute site. This is a subtle but important part of our recipe for success: faculty can create their own "empires" that reflect their own unique approaches in their home laboratories, but they learn that they need to pursue a different and highly collaborative approach, consistent with our more entrepreneurial culture, if they want to establish operations at the Institute site and become an active member of our community.
The Institute currently has more than 350 full-time staff members, including 20 core and 16 associate faculty members, and close to 40 scientists and engineers recruited from industry, who bring significant experience in product development from a broad range of medical and nonmedical markets into our community. Core faculty members are appointed for 3-year renewable terms, while associate faculty has 1year renewable appointments. Fellows and students from different faculty laboratories are brought together and co-located at the main Insti- The consortium is structured so that faculty and staff from all these institutions and diverse disciplines can work side by side at the Institute's sites. Although we primarily focus on medical challenges, we realized that there are many technologies that exist in nonmedical areas, (3D printing-based manufacturing, for example), which could add huge value for medicine, and there are biomedical technologies (e.g., synthetic biology) and approaches that could be equally valuable for nonmedical fields ranging from energy and manufacturing to data storage. Thus, our Institute's research areas include nonmedical pursuits focused on environmental sustainability, as well as more classical biomedical research challenges. Also adding to the richness and reach of the Institute are its strong collaborations with industrial partners who offer the understanding of markets and user needs to match the breadth of applications envisioned by Institute researchers. This constant flow of people between the Institute and its many collaborating partners helps to maintain a multifaceted exchange of information, ideas, and resources, while consolidating our focus on biologically inspired engineering across the Greater Boston region and beyond.  (Table 1) The Wyss Institute also breaks down the institutional "silos" by organizing its physical space into "Collaboratories." First, we do not provide faculty members with their own independent research laboratories. Instead, our "Collaboratories" define a cohesive, open physical footprint where fellows, students, and staff from different faculty groups, ATT members and other relevant Institute staff co-locate to work on a common high value project application or major platform area of the Institute, examples of which are described below. In addition, we built cutting-edge capabilities that are accessible by all members of our community. One example is our unique machine shop, which is unlike most found in academia (and likely none in a medical school) as it is staffed by experienced, full-time engineers and houses state-of-the-art manufacturing equipment that enables fast prototyping and construction of virtually any type of device from the microscale to the macroscale. We also can build using a broad range of materials including those that are approved by the FDA for various medical applications. These capabilities allow members of our community to innovate and iterate at a rate that is uncommon for academia, which greatly enhances our ability to meet and beat milestones on both government-and industrial-funded technology development projects.

| T HE I N S TI TU TE ' S PLATFORM FOCUS A R EA S A N D I N I TI A TI V ES
The Wyss Institute's research and development efforts are currently organized around six enabling technology platforms and two crossplatform initiatives, 1 each composed of teams of institute faculty, students, fellows, and staff who develop the new cutting edge technological capabilities necessary to enable a new wave of bioinspired materials and devices. These eight focus areas provide the Institute and its collaborators with unique technical resources and state-of-the-art equipment, as well as a rich, open, interdisciplinary environment for the students and staff to learn how to translate ideas and discoveries into products with great clinical or commercial value. Interestingly, even the way in which we create these research platforms and initiatives is bio-inspired in that they are self-organizing, dynamic, and constantly evolving based on the shifting intellectual interests of our community members as well as the technical needs and challenges of the wider commercial marketplace.
Platform and project self-assembly at the Institute results from the free flow of ideas and interactions among faculty and researchers, as well as administrative and business development staff. It is amplified by a culture that welcomes exploration and taking risks, which allows our staff and researchers to pursue their "out of the box" ideas without the stigma and fear of potential failure. Through its philanthropic funds, the Institute has the ability to readily support such ideas at their nascent stage, without the need for internal grant applications that typically and kill cancer cells (Figure 4), which is currently being evaluated in a Phase I human clinical trial. 12 An injectable broad-spectrum infection vaccine is also being developed, as well as implantable biomaterials that concentrate and trap disease-related circulating T cells, which can be retrieved to gain insights into the mechanisms of action and toxicities of novel therapeutics. 13 Living Cellular Devices. The goal here is to re-engineer living cells and biological circuits to create programmable devices for medicine, manufacturing, and sustainability. An application of such devices is in the diagnostics space where synthetic gene networks composed "circuits" of re-engineered molecular components have been created to detect the genetic signatures of RNA viruses, such as Ebola and Zika, within one week after the causative agent is identified ( Figure 5). 14 On the therapeutics side, Institute researchers have engineered a genetically mutated version of erythropoietin with a weakened ability to bind to its natural receptor, thereby preventing binding to unwanted cell types and reducing potentially toxic side effects. 15 Other efforts focus on reengineering of probiotic microbes that can act as sentinels of infection or as therapeutic factories when ingested and grown inside our intestines.

| T HE I N S TI TU TE ' S TECHNOLOGY T RA N SLA TI ON M ODE L
We map all of our translational activities, from idea conception through early technical development to further technical de-risking, business development, intellectual property protection, and eventual commercialization, onto a "Technology Innovation Funnel" 1 (Figure 9).
At the broadest part of the funnel, we harness the creative freedom of academia to generate a pipeline of new ideas and potential breakthrough technologies, focus these ideas, and move them towards Concept Refinement and Prototype Optimization in collaboration with end-users, clinicians, regulatory agencies, and industrial partners who help us to best understand the market needs and problems early in this process and to inform our approach to technology development.
Most researchers do their most creative work in the "spaces between grants" because government funding often supports only the startup valuation when these projects spin out. This approach also allows them to hit the ground running with an experienced team already in place, thus greatly increasing their likelihood for long-term commercial success. Institute Projects that do not lead to a new startup are either eventually licensed, or they come to an end at the Institute.

The creation and implementation of our model of translation inside
Harvard's well-established academic environment has had its challenges.
The Institute had to find ways to develop its own unique approach to translation and creation of an entrepreneurial culture, while maintaining close connections to the rest of the university and respecting its policies.  Inc., and SlipChips Corp., and is a member of their scientific advisory boards.