Ruben Morones-Ramirez: Yes, the key points of the work are—I like to divide them in three. The first one is the basic science that we did to unravel how silver acts on bacteria. The next two points were that once we found the mechanism of how bacteria works which was through enhancing permeation of the cell or augmenting the permeability of the cell and provoking within the cell a redox reaction or an oxidated stress within the cell, we were able to potentiate antibiotics in two different ways. One if the permeability of the membrane increases then you can get a lot more antibiotics to come in and if you have an oxidative environment within the cell you can then enhance the antibiotics as well. And we were able to both enhance the antibiotics and also an important result that we show in the paper is that we senstitise bacteria that was previously resistant to antibiotics. What does this mean—which we treated bacteria that needed a lot more antibiotics than the wild type to have any effect and then we were able to get the bacteria to be sensitive again to the silver...?
Geoff Candy: Now this is clearly a hot topic in the medical community at the moment, multi drug resistant bacteria particularly Gram-negative bacteria which has an extra layer around it as far as I understand it, that makes it more difficult to treat with antibiotics. Now the research helped with that as well, as far as I understand it.
Ruben Morones-Ramirez: Yes, another core result about the research is that the negative bacteria as you mentioned, has an outer membrane that protects the cell from antibiotics, so antibiotics that are quite bulky chemically. Unfortunately vancomycin for example does not have an effect on bacteria. However after treatment with silver and implementing the permeability of the cell, you can have vancomycin which was not effective against those kinds of bacteria, to be effective again, so we get a new arsenal of antibiotics to fight this kind of bacteria.
Geoff Candy: The one drawback, and we've seen silver being used as an antimicrobial for many years now going back in antiquity, but often from what I've understood, a lot of it has been topical. The research looked at the ways it can work inside the body as well. How toxic is this as an element?
Ruben Morones-Ramirez: Yes, as you mentioned, we treated mice - we injected the antibiotics and we did toxicity studies, very thorough regarding first to see how toxic it was just to see if the mice would survive and so the concentrations at which some mice started to die was 210 and the amount that we used was 15. So there's a very long range between toxicity and what we used. The other thing is we did blood work which is usually looking at the blood of the mice and looking at a lot of the analyses that we like to see if the liver was ok and some other concerns and we thought that the mice were doing fine.
Geoff Candy: How much silver are we talking here?
Ruben Morones-Ramirez: If you do a calculation for a human being to do the concentration that we reported on the paper, you need about 250mg of uptake which is about - the Tylenol pills are usually about 100mg so half a pill of silver, and then we can have the other half to do the antibiotics.
Geoff Candy: How do you envision this kind of discovery working within the pharmaceutical industry?
Ruben Morones-Ramirez: I envision it in many different ways. There is a lot more work that has to be done regarding toxicity and regarding for example, pharmacokinetics is not the same thing to uptake antibiotics orally or injected is very different. We did an experiment with injections but I believe that we might even be able to take antibiotics and then have maybe a glass of water, with a little bit of silver which is in ionic form. So you wouldn't even have to couple with the antibiotic, so you take the antibiotic and you take a glass of water with silver or maybe even have it injected with a solution where you have the antibiotic and ionic silver which is soluble in water and you can inject the antibiotic together which is what we basically did in our study.
Geoff Candy: I suppose the big question on the minds of people involved in the silver industry is where we're going to see new uses for the metal coming from because clearly for a very long time the primary use for silver in industry was the photographic industry and that clearly has come down a lot. In terms of silver's use within medicine, within pharmacy have we just scratched the surface of its potential uses within the medical community?
Ruben Morones-Ramirez: If you do a little bit of calculations of how much 200mg per person and if you extrapolate it to how many people get infected per year, it's not very much—probably about a year you will use maybe about 200,000kg of silver, so I don't know if that's a lot or a little, but that's more or less how much you would use, and then you can always do afterwards—I know with photography you do recycling of silver, so you always get it back. So I don't see that much of a problem. Maybe we can replace that use of silver that was used for photography and it's not used in that way anymore...
Geoff Candy: But in terms of the uses for silver within medicine, are we just beginning to understand how its working and what its potential uses are?
Ruben Morones-Ramirez: Yes I think there is a lot of potential for this metal. It's a very special metal because I used to work with silver during my PhD where we also did some work on antimicrobials and we also did a report that silver in its Nano-particle form can be used to treat HIV and to treat HIV infections. So there are a lot of medical uses that I think need to be explored and right now in my lab we're doing a lot more work to treatment of infections and this permeability enhancement on bacterial cell walls, can be used for many other things, so I think we're just scratching the surface.
Geoff Candy: How far away are we from actual practical commercially viable uses of silver within antibiotics? Clearly we're already using them in plasters and bandages and that kind of thing, but at an ingestible pharmacological level, how long would it likely take before we would see the results of this kind of research coming onto the pharmacy floor?
Ruben Morones-Ramirez: These questions I always like to answer in two different ways. One way is that here in Mexico where I'm living, we use silver for a lot of medical uses, and I know in India they use it a lot too. But we usually use it as a natural antibiotic whereas a natural disinfectant for example there's a product here called Microderm that you put a few drops of silver into a bath of water and you submerge fruit that grow on the ground to sterilise them like for example strawberries or lettuce and so we use silver a lot. You can go to Stortford GNP and you can buy silver—they sell it to you as a natural antibiotic. As humans we consume silver in small amounts obviously, but we already consume silver in many different countries and sometimes in many different ways. Now there needs to be a little bit more of a formal toxicity study and see how silver basically interacts with the body pharmacokinetically and so due to all these factors I believe in two to five years we can see. . .if everything goes correct...
Geoff Candy: Which is always a big if in things of this nature, but good luck to you—I hope it really goes well and it's going to be something we follow with interest.