Caltech Fund Helps High-Tech Innovation Navigate “Valley of Death” Between Laboratory and Real World Applications

Caltech is a community filled with brilliant minds and good ideas. But sometimes it takes more than good ideas to generate world-changing technologies. Indeed, there is a well-known gap between the lab and the marketplace known as the “valley of death,” in which high-risk but potentially high-reward research can languish for want of someone to take a chance on it.

To bridge that gap, Caltech’s Rothenberg Innovation Initiative (RI²) was created in 2009 under the guidance of Larry Gilbert, the founding father of tech transfer at Caltech, and funded by the late Caltech trustee Jim Rothenberg and his wife, Anne Rothenberg.

RI² provides competitive grants for early-stage research that could one day lead to marketable technologies that are likely to benefit society. Each RI² award provides up to two years of support, with up to $125,000 in funding per year, to help researchers “de-risk” their innovations, according to Fred Farina, Caltech’s chief innovation and corporate partnerships officer and head of the Office of Technology Transfer and Corporate Partnerships, or OTTCP, which oversees RI² with Vice Provost Kaushik Bhattacharya. The goal is to help technologies mature beyond the conceptual stage to the point that it is attractive to venture capitalists and other investors.

Originally known as the Caltech Innovation Initiative, the program was renamed in 2017 to honor the Rothenbergs. The Rothenbergs had committed an additional $15 million to ensure the program’s ongoing success in March 2015, just before Jim’s sudden death in July at age 69.

“It means a lot to our family that Caltech is so committed to RI²,” says Daniel Rothenberg, Jim and Anne’s son, who is also an active supporter of the RI² fund. “Caltech has some of the brightest minds, and it is nimble enough to fund projects and see them through. That’s why my dad fell in love with the concept of RI² and supported it. Today, we’ve had great success thanks in part to the many people who have taken it far beyond our early ideas and even farther beyond the expanded funding our family committed a couple years ago. We want to push to the point where all Caltech faculty and staff have the ability to see their home-run ideas come to fulfillment.”

Projects previously funded by RI² include research by Sarkis Mazmanian, the Luis B. and Nelly Soux Professor of Microbiology and a Heritage Medical Research Institute investigator, who showed a connection between bacteria found in the human intestinal tract and disorders of the central nervous system, such as autism spectrum disorder, Parkinson’s Disease, anxiety, and depression. RI²2 support allowed Mazmanian to test oral treatments in proof-of-concept animal trials that ultimately attracted venture capital funding, enabling the founding of Axial Biotherapeutics with $19.15 million in funding at the end of 2016.

Caltech faculty can submit one idea per year to the program. Applications are reviewed by a committee consisting of Caltech faculty, members of OTTCP, and members of the venture investment community. Proposals are required to be simple: a maximum of four pages with answers to 12 brief questions, including what the project will be, what milestones can be achieved with RI2 funding, the unmet need in the marketplace, and commercialization plans for the technology.

What makes it work so incredibly well is that “it is the least bureaucratic process that any faculty member has to deal with in terms of raising money for their research,” says Richmond Wolf (MS ’94, PhD ’97), former director of Caltech’s Office of Technology Transfer. “What we are looking for is high risk super high return ideas that otherwise might not get funded. We don’t ask that you’ve done two to three years of research already. We ask that you dream about science and engineering that can change the world and yield economic benefit.”

The committee is tasked with deciding which promising ideas will receive funding. The RI² program receives more than 20 proposals every year, of which about a third are funded.

For 2018, eight projects received RI² funding:

• a new method for figuring out which antigens are being targeted by the immune system’s T cells. The method—developed by David Baltimore, president emeritus and the Robert Andrews Millikan Professor of Biology—could identify whether those T cells are misfunctioning, potentially leading to autoimmune diseases;

• a system for diagnosing many diseases from just one blood draw, using single-cell messenger RNA profiling of the immune system. The system was created by Sisi Chen, senior research scientist, and Matthew Thomson, assistant professor of computational biology;

• a wearable band invented by Wei Gao, assistant professor of medical engineering, to provide noninvasive monitoring of stress and depressive disorders by tracking changes in sweat;

• a low-cost wearable “smart patch” that measures the physiological stress on athletes and patients suffering from chronic health conditions, developed by Axel Scherer, the Bernard Neches Professor of Electrical Engineering, Applied Physics and Physics;

• a project by Professor of Chemistry Brian Stoltz to develop anticancer drugs from bis-tetrahydroisoquinoline chemicals, natural compounds known for targeting the DNA in cancer cells;

• “Turnkey,” a technology that would provide frequency-agile optics on a chip for medical diagnostics, information technology, cybersecurity, and metrology, developed by Amnon Yariv, the Martin and Eileen Summerfield Professor of Applied Physics and Electrical Engineering;

• a project developed by Frances Arnold, the Linus Pauling Professor of Chemical Engineering, Bioengineering and Biochemistry, to engineer enzymes that create amino acids that do not exist in nature for use in pharmaceuticals and as catalysts;

• and an ultra-portable three-stage ozone-assisted nano-filtration (ULTRON) device for off-the-grid wastewater treatment, created by Michael Hoffman, the John S. and Sherry Chen Professor of Environmental Science, and Kai Liu, postdoctoral scholar.