Hearing loss restored through gene therapy, app-controlled hearing aids, and synthetic biology takes off.

12 May 2014

Once upon a time, prosthetic augmentation of a failing sense of hearing took the form of devices the size of a paperback book hung around one's neck and smallish headphones pumping amplified sound into the wearer's ears. As technology progressed and the sizes of components shrank to sub-surface mount form factors (for illustration please note the sizes of the 603 and 402 components) hearing aids shrank in size until they could be custom molded to fit snugly into one's ear canal. All of the benefit with very little of the mass or weight. Hand in hand with the miniaturization of this technology came the problem of how to adjust and control such a device. For example, hearing aids like my grandfather's have a single dial to control the volume operated by twisting one's fingertip. Mind you, that dial only controls the volume and power state (i.e., on or off) and no other aspects of the diminutive units' operation. Perhaps borrowing the Bluetooth radio functionality of cochlear implants, the latest generation of hearing aids can be slaved to the user's iPhone and adjusted minutely with an app. Former pastor Dick Loizeaux was field testing a latest generation hearing aid in a busy New York City nightclub, and used the app to favor one microphone in each unit over another, turn up the gain on the forward microphones, filter out the bass in the music, and use the directional functionality of one of the hearing aids to hold a surprisingly coherent conversation with someone else at the club. In addition, by slaving the hearing aids to one's phone the user is able to run calls directly into them as if they were a Bluetooth earpiece or headset. The apps even have graphic equalizer functionality, so you can fine-tune how things sound on the user-side of the hearing aids. Fascinatingly, the costs of these new hearing aids (the units mentioned by name in the article cost $2kus and $3kus, respectively) are slightly less than half what my grandfather's hearing aids cost apiece. Some days, I just love the technology curve.

One of my chief concerns, however, is relative lack of security of Bluetooth as a technology, but that's outside of the scope of this post. Besides, .ronin can discuss it better than I.

In the summer of 2014, just a few months hence, a new application of gene therapy is slated to begin clinical trials. Following positive experimental results in laboratory mice that had their hearing damaged through the administration of extremely powerful antibiotics and subsequently partially restored, a new bioengineered virus will be used to attempt to reverse acute deafness in humans. A gene called Ad28.gfap.atoh1 controls the development and regeneration of hair cells in the inner ear which are responsible for converting pressure waves in fluid into electrical impulses that are interpreted by the brain. The virus (probably a type 35 adenovirus with an inability to replicate in vivo) contains new copies of the Ad28.gfap.atoh1 gene; the procedure will involve surgical administration of the virus directly into the inner ears of patients that have lost almost all of their hearing but who also still have functional auditory nerves. Interference with any residual hearing is a concern, so the members of the test group will have as little hearing left as possible. Restoring hearing lost from chemotoxic damage is a fairly imporant and interesting thing these days because most cases of it are due to exposure to extremely powerful and dangerous antibiotics, which unfortunately are becoming more and more necessary due to outbreaks of bacteria resistant to most of the commonly used antibiotics more and more often. It seems as if advances in synthetic biology are taking place faster than we can keep track of them. In recent years we've seen the creation of artificial chromosomes, bacterial DNA written from scratch, and the synthesis of novel nucleotides found nowhere in nature. It's the last advance that's of particular interest at this moment - bacteria whose genomes incorporate those synthetic nucleotides are now alive and well in the lab. The synthetic nucleotides, named d5SICS (or 'X') and dNaM (or 'Y') add two more letters to the A, C, T, and G of DNA on Earth. A bioengineered strain of the bacterium e.coli was exposed to plasmids that contain snippets of DNA that include a single X-Y base pair (be careful, let's not confuse the new base pair with X or Y chromosomes (great... first some programmers think it's cute to use ambiguous variable names, and now we're going to have the same problem with gengineers. What could possibly go wrong?)). The e.coli cultures sucked the plasmids into their internal environments and incorporated the synthetic genetic material into their DNA without seeming to notice the third base pair. Even more interestingly, the new X-Y base pair appears compatible with e.coli's DNA replication mechanisms, meaning that as long as the bacteria has a ready supply of the d5SICS and dNaM nucleotides those base pairs will be copied along with the A-G and T-C base pairs when the bacteria reproduce through division. The next logical step involves figuring out how to write brand new genes that use the third existing base pair. Engineering organisms that normally synthesize d5SICS and dNaM alongside guanine, cyotisine, adenine, and thymine to make the organisms self-sustaining (so that external supplies of the new nucleotides are not required (thought that would make a handy control mechanism over the organisms...)) seems like another supporting step in the process of practical synthetic biology.