Wyss directors share the unique aspects that make the Institute successful in new review article
By Lindsay Brownell
(BOSTON) — In the eight and a half years since it was launched, members of the Wyss Institute for Biologically Inspired Engineering at Harvard University have published more than 1,700 scientific articles, submitted over 2000 patents with 120 already granted, launched 20 new startup companies, and closed on 9 licensing deals. Their collective achievements have spurred hundreds of inquiries from industry, governments, universities, and other organizations worldwide seeking to learn about the unique organizational model upon which the Institute is based. “It was timely that we were asked by Bioengineering & Translational Medicine to write a review article outlining the Wyss model. We have learned a lot from successes and challenges alike as the Institute has developed from an idea on paper to a full-fledged scientific powerhouse,” says Wyss Operations Director Mary Tolikas, Ph.D., M.B.A., who co-authored the paper along with Wyss Administrative Director Ayis Antoniou, Ph.D., M.B.A., and the Institute’s Founding Director, Donald Ingber, M.D., Ph.D. The article appears in the journal’s August 2017 issue.
The Wyss Institute was founded in 2009 based on the belief that science has uncovered enough information about how Nature builds, controls, and manufactures that its biological principles can be leveraged to develop new engineering innovations to solve some of the world’s most intractable problems. This new approach has become known as “Biologically Inspired Engineering.” The Institute’s founders envisioned a research organization that combined fundamental research into Nature’s innermost workings, down to the nanoscale, with out-of-the-box thinking and a focus on translation, which could turn those evolution-tested ideas into useful new products, technologies, and approaches.
1/8 Fluorescent in-situ sequencing (FISSEQ) pinpoints the location of thousands of mRNAs at once in a slice of mouse brain, allowing scientists to determine both where they are and the sequence of bases that identify each one of them. Credit: Wyss Institute at Harvard University 
2/8 The SEM image on the left shows extracellular matrix material (yellow), red blood cells (red), immune cells (blue), and infectious S. aureus bacteria (green) deposits on a commonly used, supposedly non-stick Teflon surface implanted into S. aureus-infected mice. The SEM image on the right (colored purple) shows the same Teflon surface treated with the Wyss’ SLIPS coating within the infected mice, notably lacking cell or extracellular matrix material deposition. Credit: Wyss Institute at Harvard University 
3/8 The Wyss Institute’s Mobility Enhancing Soft Exosuit is a soft wearable robot made from lightweight and flexible materials that moves with the body to produce improved movement support. Credit: Wyss Institute at Harvard University 
4/8 This disk-shaped, biodegradable sponge contains growth factors and components of a cancer patient’s tumors that reprogram the immune system to attack cancer cells. It is now in clinical trials to treat melanoma. Credit: Wyss Institute at Harvard University 
5/8 Organs-on-chips, including a human lung model (right), offer a method to more easily visualize and study both healthy and diseased human organs, as well as evaluate their response to drugs, creating the potential for a lower-cost, faster alternative to clinical animal testing. Credit: Wyss Institute at Harvard University 
6/8 Wyss Institute scientists have embedded effective synthetic gene networks in pocket-sized slips of paper. An array of RNA-activated sensors uses visible color changing proteins to indicate the presence of a targeted RNA, capable of identifying pathogens such as antibiotic-resistant bacteria and strain-specific Ebola virus. Credit: The Wyss Institute at Harvard University 
7/8 Self-assembling nanocages built from strands of DNA (above) could one day deliver drugs, or house tiny bioreactors or photonic devices; a superresolution microscopy method developed at the Wyss Institute, DNA-PAINT (below) visualizes structures using short strands of DNA (yellow) labeled with a fluorescent chemical (green) to bind and release partner strands on the cages’ corners, causing them to blink. Credit: Wyss Institute at Harvard University 
8/8 3D printing techniques using “fugitive ink” (far left image) are being used at the Wyss Institute to create devices that mimic the function of human tissues and organs; in this case, the hollow, convoluted tubules found in the kidney (second from the left. The tubules are seeded with fully differentiated, living human epithelial cells (far right image), forming a functional, 3D architecture (second from the right) that can be used for drug testing and development. Credit: Wyss Institute at Harvard University
A crucial requirement for achieving that goal, however, was to address the pitfalls typical of academic institutions that delay or prevent breakthrough discoveries from leaving the lab. The Institute was launched with a $125 million gift to Harvard University from its namesake, Swiss entrepreneur and philanthropist Hansjörg Wyss, who wanted to see “an innovative startup in the world’s greatest academic environment that will take risks and have positive near term impact on the world.”
To execute on Wyss’ vision, the Institute enlisted fourteen of the most brilliant, innovative, and entrepreneurial faculty from Harvard University and its collaborating institutions as its Founding Core Faculty members, each of whom retained their academic appointments at their home institutions while also conducting research at the Wyss. “This is a subtle but important part of our recipe for success,” the authors write. “[The faculty] 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 and become an active member of our community.”
One of the most important elements that the Wyss seeks to cultivate is cross-disciplinary collaboration, which it achieves in part simply as a result of putting people with diverse interests (synthetic biology, polymer plastics, robotics, inorganic chemistry, physiology, surgery, etc.) in close working proximity to one another. These scientific and engineering efforts were then complemented by the recruitment of close to 40 staff scientists and engineers to an Advanced Technology Team (ATT), each of whom bring years of prior experience in industry and product development to the Wyss community. These ATT members integrate directly into research teams and help them focus on applications, intellectual property generation, and commercialization using approaches more commonly found in a start-up environment. Their expertise in developing timelines and meeting milestones has enabled Institute researchers to innovate and meet program goals at a pace and focus rarely seen in academic settings. The Institute then brings in additional team members with experience in business development as well as entrepreneurs-in-residence to further bolster these efforts. In this manner, the Institute harnesses the creative freedom and flexibility of academia while maintaining a focus on translating its discoveries into technologies that can have positive near-term impact on the world.
The Wyss Institute’s research and development efforts are organized into six technology platforms and two cross-platform initiatives, each composed of faculty, students, fellows, and staff, that provide a rich, open, interdisciplinary environment. These eight focus areas span a wide breadth of fields: Adaptive Material Technologies, Bioinspired Soft Robotics, Biomimetic Microsystems, Immuno-Materials, Living Cellular Devices, Molecular Robotics, Synthetic Biology, and 3D Organ Engineering. “The organization self-assembled organically based on the people we were working with and their interests and passions. The concept of platforms and how ATTs would be integrated into our efforts were actually not in the original proposal, but over time it became clear that they were needed to move the Wyss’ mission forward,” says Wyss Founding Director Donald Ingber, who is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and the Vascular Biology Program at Boston Children’s Hospital, as well as Professor of Bioengineering at Harvard’s John A. Paulson School of Engineering and Applied Sciences. “The current platforms and focus areas, like all aspects of the Wyss Institute, are a reflection of our community’s priorities in the present moment, and if we are to continue to be successful, they will need to change in the future as our capabilities grow and evolve.”
Each translational activity that arises within the platforms is mapped onto a “Technology Innovation Funnel” that guides it from idea conception through de-risking and eventual commercialization in collaboration with end-users, clinicians, regulatory agencies, and industrial partners who contribute insights to inform its development into a viable entity. Technologies that pass successfully through the funnel are usually licensed to established companies or new start-ups that are spun out of the Institute. Some high-potential-value ideas that have significant interest from investors and strong intellectual property become “Institute Projects,” which receive additional financial support and access to other resources to further validate the technology technically as well as commercially, thereby giving them a higher likelihood of commercial success than is typical in academia. Some examples of companies that have completed that transition include Emulate Inc., ReadCoor Inc., Opsonix Inc., and SLIPS Technologies.
The continual growth, development, and migration of ideas, products, and companies out of the Wyss Institute to start life in the “real world” allows for a constant influx of new people and projects to take their place, allowing the Institute’s focus to evolve, keeping it vibrant. “What really makes the Institute successful is its people and the culture that has grown up around their shared passions and goals,” says Administrative Director Ayis Antoniou. “It’s a unique, cross-disciplinary environment where risky ideas are encouraged, new ideas are harnessed and incubated quickly, and every success and failure is accepted and turned into a learning opportunity that helps the Institute continue to grow and succeed.”
