Valerie Gray Hardcastle
Institute for Health Innovation
Northern Kentucky University
I agree that novel tool use is connected to significant conceptual and theoretical advancement in science. Indeed, I believe that technological advancement is the primary limiting factor in neurobiological theory development. But how it is connected can differ depending on the specifics of the case. Sometimes novel tool use drives hypothesis-generation; but sometimes it drives hypothesis-testing. What I present below is a textbook case of How Science Works in the old-fashioned sense: researchers working to find the right tools to peel the lid off a black box to support a previously developed hypothesis. (This is a summary of some of the work my co-author Matt Stewart and I describe in chapter 5, “A Different Role for Tinkering: Brain Fog, COVID-19, and the Accidental Nature of Neurobiological Theory Development.”)
Tool development is a fundamental aspect of the neuroscientific trade. And theories are just another tool that neuroscientists utilize when poking about in the brain. They are a utensil, just like a microelectrode, with which we use to probe our grey matter. I illustrate this perspective by recounting a recent discovery of COVID-19’s impact in the brain.
COVID-19 has been billed as a respiratory illness. This description is not entirely off the mark, as SARS-CoV-2 is primarily transmitted by breathing in the virus from the air, and it does indeed bind with the epithelial tissue found in lungs. However — and the import of this point was originally missed in the first few months of the SARS-CoV-2 outbreak — epithelial respiratory tissue is found outside the lungs. Respiratory tracts do more than support breathing; they also remove waste brought into the body along with the air we need to function. For example, in addition to smelling the world around us, the epithelium in the upper nasal cavity make mucus, which traps dust, pollen, dirt, and other unwanted particles breathed up from the nose, and then sweeps this mucus to the back of the throat to swallow down as our own internal garbage disposal system.
A similar process occurs in our lung epithelium. It also produces and secretes mucus to trap pathogens and debris within the airway, and then sweep the trapped debris across the airway tract to the back of the throat, where it too is swallowed down. But the nasal passages and the lungs are not the only epithelial respiratory tissue in our bodies. Our middle ear and mastoid also have a respiratory function. The mastoid bone is lined by modified respiratory epithelium, and, just like our sinuses, the mastoid produces mucus and, in conjunction with the middle ear, sweeps ear detritus trapped in the mucus through the Eustachian tube to the back of the throat for swallowing.
We know that SARS-CoV-2 can infect the epithelial respiratory cells in the lungs, which causes shortness of breath. We know it can infect the epithelial respiratory cells in the sinuses, which causes the loss of smell. It therefore stands to reason that SARS-CoV-2 could affect the epithelial respiratory cells in the ear too. And if it can infect the mastoid, then perhaps it could also impact the central nervous system in analogous fashion to what happens between the nasal cavities and olfactory bulb projections.
Significant numbers of COVID-19 patients report sudden hearing loss, vertigo, or tinnitus among their symptoms. We also see longer-term effects on the auditory system for patients, including earaches, vertigo, loss of hearing, and, importantly, tinnitus. Problems with hearing or dizziness generally reflect a challenge in the inner ear, but tinnitus is a central phenomenon, for its sufferers perceive sounds when they are not present, and sound perception requires the involvement of auditory neurons.
To test the hypothesis that SARS-CoV-2 can infiltrate the auditory system, one must examine the inner ears and brains of COVID-19 patients. But doing so presents immediate technological challenges, for there is no way to do this non-invasively in live patients. At the same time, there was no good way to do this in deceased patients either; due to restrictions by the Center for Disease Control and Prevention (and common sense), routine autopsies cannot be performed on the brains of deceased COVID-19 patients because they use instruments that generate wicked aerosol spray.
A new approach was needed — a different way to access brains that did not utilize contemporary instrumentation. This was the challenge that confronted Dr. Matthew Stewart, the otolaryngologist on the research team investigating this idea. He needed to devise a way to access human brains that would not risk infecting himself or others with SARS-CoV-2. Stewart and others had a pretty good story that could explain why some COVID-19 patients had auditory symptoms; they just needed to find proof of its truth. Notice that, in this case, hypothesis-testing is driving tool development.
To cut to the end of the chase, Stewart used old 1930’s pre-electric surgical tools for autopsy. And he discovered that decedents who had died from complications of COVID-19 exhibited a very strong positive result to the PCR test for SARS-CoV-2 in their ears.
But there is more. Stewart and others also had good reason to suspect that SARS-CoV-2 was infiltrating epithelial tissue in the inner ear. But to confirm this suspicion, they would need to determine whether so-called ACE2 receptors, which SARS-CoV-2 binds to, are present in the tympanic cavity. The natural approach would be to use electron microscopy, but that was problematic because the bones our ear are among the hardest in our bodies, and the decalcification process required to soften them enough to be able to slice them for microscopy examination normally takes ten months – much too long in the race to figure out COVID-19. But once again, Stewart adapted techniques from another era used for other purposes. In this instance, he harked back to his undergraduate chemistry lab and adapted the old techniques used to decalcify rocks. Here again, we see theory driving tool innovation and not the other way around. The desperate need to uncover the sequelae of COVID-19 drove tool use.