An Ode to Philanthropy
More than 30 years ago, several researchers reported that chickens and quails could naturally recover from noise-induced hearing loss. This recovery is based on the activation of stem cells that reside in the bird’s inner ear. About seven years ago, we became interested in the amazing regenerative potential of the avian inner ear. At that time, we were mainly banging our heads against a wall, aiming to make potential inner ear “replacement cells” from mouse and human stem cells, but the efficiency, purity, and quality of the cells were not improving despite investing many years of work.
We decided to use single-cell RNA sequencing, a very new method back then, to characterize the cells in the chicken inner ear and to measure changes in almost 20,000 individual genes in individual cells as they respond to hair cell loss. This led to a modestly starting but constantly progressing research program culminating in multiple significant publications. Here is a link to a short blurb I recently wrote for the Hearing Health Foundation summarizing our successes thus far.
This progress did not come automatically. A soft-money-funded research lab cannot afford to build a team (“team chicken”) with at least three dedicated researchers and use expensive state-of-the-art technology. Luckily, I could excite several postdocs to work on the avian inner ear. Mirko Scheibinger obtained a 2-year scholarship from the German Science Foundation; Daniel Ellwanger, a bioinformatician who had just graduated, decided to take risks and join a basic biology lab. A colleague at OHSU, Peter Barr-Gillespie, started collaborating, and we owe a lot of insight and help to troubleshoot isolating avian cells and brainstorming. Then, two additional postdocs, Amanda Janesick, and Nesrine Benkafadar, joined the team, which then accumulated enough knowledge, experience, and team spirit to perform an amazing 1.5-year data acquisition experiment. They conducted countless surgeries on chickens, isolated cells, and checked for quality, again and again – until we were convinced that our single-cell data acquisition works and that we get meaningful results. If it were not for this pioneering group, we would not have made the scientific discoveries of recent years.
Now, this endeavor was expensive. I mentioned that we started with a postdoc fellowship and several additional fellowships, but they did not allow us to expand. I submitted countless grant applications to the NIH, which were all turned down by reviewers stating that “this is a waste of money – chicken work was previously well supported, but nothing came out of it.” Appeals to the program officers at NIH, reminding them that 99% of previous funding went to mammalian research, which – frankly – also had not produced great insight into hair cell regeneration, did not work. NIH would not touch this with a 10-foot pole 3-5 years ago.
However, the Hearing Health Foundation and donors to the Stanford Initiative to Cure Hearing Loss (SICHL) saw the potential, and they helped us to provide salaries to postdocs, allowing us to run dozens of single-cell RNA-seq experiments (at $10,000 a pop). The Hearing Restoration Project (HRP) of the Hearing Health Foundation gave us a scientific home for monthly brainstorming sessions with colleagues at other institutions and a more sustained funding model. Without philanthropic support, we would have been dead in the water, and our avian model system would not be as advanced as it is now. Finally, the NIH woke up, and we are now well-funded to move this work forward. I am not bitter about NIH and the reviewers who initially did not see the potential of this work – NIH is the institution that allowed us to expand further and to accept new postdocs and graduate students into our team chicken: Austin Huang and Lyn Miranda Portillo. We are actively searching for an additional postdoc to join the team! Philanthropy made all this possible.
We are deeply grateful to our donors for their generous support of our SICHL initiative. Your contributions have been instrumental in advancing our research and bringing us closer to our goal of curing hearing loss. We could not have done it without you!