Appendix 11: Keithley Updated Comments

Source:

Current funding for temporal bone labs is derived from private donations and NIH R01 or other grant or contract mechanisms.

I propose that NIDCD, under renewable contracts and based on productivity, provide existing laboratories with "overhead" funding to maintain the collection and processing of human temporal bones.

Needs Assessment:

1. The greatest need for a temporal bone laboratory is trained personnel. The techniques for handling temporal bones are unique and require a great deal of skill. The anatomy is complex. It is important to maintain the people who are trained in those skills. It is also necessary to train new people who are familiar with molecular biological techniques to use these techniques on temporal bone samples.

2. The cost of collecting (dissection from cadavers) temporal bones has risen in the past several years. It now costs between $300 and $500 for 2 bones from one cadaver. This is an "overhead" expense that needs to be guaranteed if temporal bone research is to continue.

   Supplies are also needed, but these can usually be procured from other sources. For instance an individual with a specific scientific project that relates to temporal bones will or should have funding for that project and can provide the supplies for the project.

   The idea is that if there is an available source of temporal bones and personnel to process them, an individual or team of researchers can collaborate with a temporal bone laboratory and its personnel to investigate a scientific question. If the temporal bones are not available, individual researchers cannot easily put together the whole project.

3. A very critical need is the collection of normal temporal bones from individuals with "normal" hearing for their age. Without this normal tissue it is very difficult to establish normal values for protein expression or other measures other than anatomical structures.

4. In addition to the collection of temporal bones, other tissue that can easily be used for DNA extraction should also be collected from each cadaver.

General Ideas

Establish a collection program for the collection of tissues/temporal bones from individuals with congenital hearing loss and other forms of genetic hearing loss. The current collections contain few of these bones.

Here is an attempt at identifying meaningful reasons for studying temporal bone pathology and keeping the art alive.

There are very few cases of pathology from syndromic and non-syndromic hearing loss cases in which underlying genetics have been identified. The absence of pathology will always hamper efforts to treat the patient.

Still need to evaluate cochlear implant pathology.

When otologists are in a position to clinically utilize new technologies that evolve from stem cell, viral vector, and growth factor research, there needs to be the infrastructure still in place to evaluate the results of these technologies on the inner ear. Perhaps the first cases will be elderly people who have lost their hearing and are willing to be experimental subjects.

Training of Temporal Bone Researchers--Funding and Needs

1. Training grants could be offered to existing TB researchers to train young investigators

   1. Fellowship for US trained otolaryngologists

   2. For Ph.D. candidates (course work payment and stipend) so they would receive TB training in conjunction with another course of study such as neuroscience, molecular biology, molecular genetics, or medical sciences with a specialty in pathology. It is possible that developmental geneticists could be attracted to the inner ear as a system with many mutations and phenotypes.

2. In an effort to train existing researchers about the importance of temporal bone research, a conference could be given or a symposium at the ARO meeting with a focus on Animal Models--How well do they model the Human Condition? In this way the human temporal bone can be made to be the most important component of research, not just the dinosaur.

   Scientific issues would be:

   1. Comparison of structure between the human and various mammals used for hearing research, examining the differences in the structure/function relationships.

   2. Comparison of genes (mutations and knockouts) between mammals and humans. This can be related to phenotype in the different species.

   3. Comparison of protein expression and localization between humans and animals

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