ECM - a light based tissue

Brian Ward ex CEO of NZ Bio and the development of an extracellular matrix scaffold. ECM = E = MC^2 its a light-based tissue

As I had spent approximately six years working in the field of extracellular matrix and wound healing I had developed considerable expertise in understanding the properties of extracellular matrix proteins. Dr Brian Ward came to Industrial Research Limited and he wanted to develop an intact extracellular matrix wound healing product similar to that produced overseas called SIS porcine submucosal intestinal membrane. The competing product Brain used when he was a vet in treating wounds in pets. We initially explored both calf stomach and sheep stomach but quickly realized that the calf stomach was very difficult to work with so we quickly shifted our focus on sheeps rumen. These were large. I considered the biological function of a stomach as a bag that performed absorption. I then decided to look at the use of osmosis to facilitate the processing of the tissue. When water was placed on the inside of the tissue and a salt solution was placed on the outside of the tissue the fluid flow occurred in the direction of normal stomach absorption. This rapidly softened the epithelium and muscle layers from the extracellular matrix material. The muscle was readily removed with a gel knife and the epithelium was also easily removed. Such a simple osmotic process lead to a great outcome. However, when the tissue orientation was switched with respect to osmotic flow the tissue became dehydrated. So this did not appear to be simple osmotic flow after all. What was going on was not obvious at the time and something that I did not understand for some considerable time. Hindsight is a beautiful thing and having time to look back over past projects to see why thing worked well and why the certain thing did not go well has been helpful in refining and developing an experimental process. This also helps you evaluate your knowledge growth from how you viewed the technology at the time of the work versus at a later date.

My other major contribution to the production of the ECM product was related to the removal of the epithelial layer. Brian's Dad had developed a machine made with two circulating tyres that were on top of each other and that spun around in equal and opposite directions. Brian's Dad was putting the ECM with epithelium up on a board and trying to pass it in between the two tyres. The tissue just balled up and no evidence of the epithelium removal was observed. Brian, his Dad and I discussed the issue and then I asked to have the piece of tissue and the board. I wrapped the tissue over the end of the board so that it was symmetrical and then pushed it in between the two tyres and out the other side of the tyres came a clean ECM product. The proof of concept was obtained. The nature of the rumen is that it contains symmetrical pockets that can be cut open and a template board slipped into the pocket in order to fit neatly inside the rumen. This was done in order to facilitate the removal of the epithelial layer.

One of the funny things Brian attempted in order to remove the epithelial layer was the use of a mould and a water blaster. It tore shreds off the tissue and it blasted it everywhere. It got stuck in the bushes outside the laboratory. This approach appeared to be only useful for fertilizer production. So that was one avenue that we quickly dismissed as a dead end. I wonder if he still has the template.

I was asked by Brian if I would like to come and join the company and this was something I discussed with my wife and others that I trusted. The decision was made to stay at IRL due to the high risks associated with a start-up company. Looking back now, that was a big decision but I still think I made the right decision. Family life is based in Wellington so the move North to Auckland that Mesynthes did would have placed a strain on my life that I would not have been willing to take so I would have had to leave if I had joined. Still, did miss out on a fun ride by the looks of things. It is great to see where they have got to in the years since those early days with international distribution into the USA and FDA approval and reimbursement of the products. The team have done a great job and they moved from Wellington to Auckland to be able to expand and obtain the skilled workforce needed to grow as a company. I feel proud to have had a small but significant part to play in the early stages of Aroa development. It is good to see what can happen when good people get together and are allowed to be creative and solve challenging problems using a biological understanding of biological tissue. Brian gave me the vision and let me have the freedom to create the process. I do not follow literature methods as that is a constraint. I come from first principles and use evolutionary approaches to adapt technologies to solve real-world problems.

Later on, in my career, I looked back at this work and considered the directional flow of water through the stomach. It appeared that the stomach was alive even after it had been taken out of the animal. What was going on seems to be too strange but I can only suggest the following. I think the tissue itself is capable of splitting water on the side of the stomach or there is some kind of directional pumps that takes water through the system. It is a facilitate flow in a directional manner. I have been considering absorption for some time and I thought it would be interesting to think about what happens when you light a candle. Obviously, the wax melts and then it becomes volatile and the wax mixes with oxygen and a chemical reaction occurs that breaks bonds in the wax, which produces light and heat and carbon dioxide. Interesting how light is produced by breaking bonds. Does that mean that the bonds that hold atoms together are made of light? That got me thinking more about what is light. Electromagnetism and the duality of light. After a lot of studies and some insight, I considered light to be able to hold atoms together in molecules. So when a candle is burned it was releasing those electrons in the bond and making new molecules and in the process releasing photons of light which is part of making new bonds of lower energy. The spectrum of light produced is related to the differences in the electronic configuration of electrons in the wax compared to the carbon dioxide. So if breaking bonds produces light, does this occur when our enzymes break bonds in our stomach and intestines during digestion? It would be pretty cool if internally we were producing light through bond breakage. It may be that this light is not at a wavelength that our eyes can see as this is such a narrow region of the electromagnetic radiation spectrum. However, it would suggest that an intact digestive tract would not be an issue for the transfer of light from the digestive tract to inside the tissue and into the portal vein. Some people may think this is a strange idea but a leaky gut is a bad thing. As we carry around so many bacteria in our digestive tract it may be a smarter biological process to transfer light from one side of a membrane to another. The thickness of tissue in the digestive tract is very thin and it contains windows that are essentially see through. Why do we have windows in our houses? It is to let the light in and to look outside. This may be the same reason why there are windows in our intestinal tract.

So is water split and transferred through the stomach as light. This is again not that silly an idea. If you consider what bonds are made of and how light appears to be produced from matter so that we can see it. You only need 4.8 eV to split water into hydrogen and oxygen. The stomach is acidic so there are more hydronium ions present. Does this make it easier to split the photon of light from the acidified water? When we eat food we appear to release heme breakdown products in both the urine (yellow) and faces (brown) which could be involved in water recovery. Water is a precious commodity so not recovering it is a bad idea in evolutionary terms. I, therefore, think it is possible that there is sufficient energy in the tissue to split water and transfer the water as the light from one side of the tissue to the other. What wavelength of light this relates to I am at this stage unsure but the placement of photodetectors on one side of the tissue could be used to determine if such an event is occurring.


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