The carbon monoxide story. Part 1.0 "So ... Can You Use It to Cure Something?"
Carbon monoxide story continued from here.
It started with an interest in measuring bronchial* tone. The trachea* and the bronchi are not just passive tubes: they actively constrict and dilate. If they bronchi constrict too much (bronchospasm), they would obstruct gas entering and leaving the lung, making it difficult to breathe and causing wheezing and whistling noises in the lung. If we were to measure how bad the bronchospasm was, or the effectiveness of drugs in relaxing the bronchi, we would need to be able to measure their diameter. No one can do that. The best we can do is estimate the resistance to air flow which is not a very precise measure.
In the early 1990’s I had a little self-funded informal lab staffed by volunteers. The younger set was made up of my friends’ kids Arie Robicsec, Josh Rucker, Alex Veseley, Ron Somogyi, David Preiss, among others. I also had a crucial helper who could do/make anything: George Volgeysi. He was a brilliant, inventive semi-retired biomed engineer that had worked at Hospital for Sick Children where he produced brilliant inventions. Now he worked with me to spruce up obsolete equipment we bought on the internet or inherited from labs that were discarding them because they didn’t work or were obsolete.
I had this idea of using the changes in diameter of the trachea as an index for changes in bronchial diameter. The idea was to fill the cuff of an endotracheal tube with water, place the endotracheal tube in the trachea of an anesthetized dog. The tubing used to fill the cuff was then attached to a column filled with water. When the trachea contracted, it would squeeze the cuff and push the water up the column. When it dilated the water would flow back into the cuff. Initially we measured changes in the heights of the water column. Then George made a side port to the column and hooked it up to a pressure transducer. The more sensitive the pressure transducer, the wider we made the tube holding the column of water. As such we were able to measure large changes in diameter of the trachea with tiny changes in the height of the water. This way we could say that the pressure on the trachea remained constant despite its change in diameter. The changes in diameter would be a precise, reproducible way of measuring the tone in the bronchi.
Eventually we determined that the tracheal diameter could change by up to 1 cm—and we could measure that in 0.01 cm increments. We used this assay to totally understand how the trachea (and the bronchi) responded to many stimuli, including irritation of the nose, smell (opening a bag of potato chips in the room!), and different aspects of breathing. We also discovered that the trachea had stereotyped responses to changes in the CO2 concentration of the blood. We tested all these in order to designate the standard conditions for testing the effects of drugs. We had one more issue to sort out: the trachea responded to large breaths, rapid breathing AND to changes in CO2. Since breathing changed CO2, to identify the effects of breathing alone we needed to devise a way to keep the CO2 constant regardless of breathing. We did. It was simple but as far as we could tell no one ever did that before. About 2 years later a well known researcher from Harvard published a very similar method in the Journal of Applied Physiology. Fortunately, 3 weeks before that, we had submitted our idea to the Canadian and US patent office.
Yes, our work on bronchial tone was a true “first” and pioneering work. It was useful and had great potential. And yes, we published some of it in excellent journals. But, other than my mother and my students, no one seemed to care. No one read the publications. No one asked us about the work. No one stopped by at our posters at conferences—no one. No granting agency would give us a cent so I had to continue to use my family’s income to support the work.
One day I was on the subway with my son Arie, who was an undergrad at U of T. In frustration, I lamented about the lack of interest in this wonderful important work. Maybe it was because I wasn’t a real scientist, and neither were my crew. My son Arie then said: “Well, is there some other application of these methods that people would be more interested in, like instead of testing things, maybe curing something?”
I said sure, it had all sorts of applications. He said “like what?”. I said, “like…accelerating the elimination of carbon monoxide from the lung.” He said “so…?”
Read More in Part 1.1
Dictionary:
Trachea: the main breathing tube from the back of the throat going into the lungs. It then branches into bronchi, which keep branching, generation after generation, and after about 17 generations of branching it ends in little sacs: the alveoli.
Alveoli: little sacs that air enters. There is a network of tiny blood vessels in their walls. This blood comes from the rest of the body. The carbon dioxide produced in the body diffuses out of the blood vessels and oxygen is taken up. The blood circulates back to the body, bringing oxygen and taking up carbon dioxide.
