Episode 10: A Creature, Who Gets A Bad Rap, Shows Tremendous Promise In Wound Care

Hello and welcome to The Better Biome Podcast, where we explore the universe within.

We're your hosts, Dr. Nicole Beurkens —

And Kiran Krishnan.

And on today's show, we're talking with Dr. Ron Sherman about using Biotherapies to improve human health. Dr. Sherman earned degrees in Entomology and Medicine, before going on to study Tropical Medicine at the University of London. Long interested in maggot therapy, he initiated the first clinical trials of maggot therapy for wound healing in 1990, during his fellowship in Infectious Diseases. Dr. Sherman joined the faculty at UC Irvine to study maggot biochemistry, where he also produced medicinal maggots for therapists throughout the western hemisphere. Dr. Sherman was a founding member of the International Biotherapy Society and the BioTherapeutics, Education and Research (BTER) Foundation in those roles. He has developed scores of biotherapy educational programs for therapists, patients, and the public at large.

He is credited with obtaining FDA marketing clearance for the first live animal [ph 'So' 0:00:59.9] regulated, and continues to advocate for other medicinal animals as well. Dr. Sherman retired from the University of California in 2008, but still teaches, conducts research, and shares his medicinal maggots with other therapists. In order to minimize conflicts of interest, he chooses to provide his biotherapy work and teaching pro bono. He earns his living in an unrelated field, working 1 or 2 days per week for the Orange County Health Department, providing medical care for uninsured HIV/AIDS patients. Such a pleasure to have you with us, welcome to the show, Dr. Sherman.

Thank you for the invitation.

This is such an interesting topic and we can't wait to dive into this. We're pretty sure that there is not very many other podcast episodes on this topic, so this is really exciting, but I'd love to start out by just having you share a bit about your journey of how you came to be interested in biotherapies, particularly maggot kinds of therapies and the work that you're doing today. How did your journey take you to this point?

Well, as you mentioned, my undergraduate work was in entomology. I then went to medical school at UCLA, where I met a plastic surgeon who was writing a dissertation on maggot therapy. He asked me to join him because I had the entomology experience. I became so interested in maggot infestation on wounds, called myiasis, and maggot therapy, that I started to collect maggots from patients that I would see over the years. I pursued a training in international health and parasitology because that was really my interest in medicine, and I also saw it as an underserved area. During my training as an Infectious Disease Fellow at the University of California, Irvine, I had the opportunity to conduct independent research. So I chose that opportunity to design some clinical trials of maggot therapy to see if it would be appropriate and useful, even today. You see, as an infectious disease consultant, I was seeing a lot of requests for antibiotics on wounds, on diabetics, for example, who have had serious limb-threatening wounds to their feet, patients with hardware, artificial joints put in that become infected, and these were often antimicrobial-resistant organisms. So they would ask for the newest and the best antibiotics, more antibiotics, [ph "3-phase' antibiotics'' 0:03:55.8] when what they really needed was removal of the dead, infected tissue, what we call debridement. So I thought this was really an opportunity for something new to treat these patients and an opportunity to do the first clinical trials, prospective clinical trials of maggot therapy. It was really the success of those trials and the realization that there was nobody at that time working in this field. That made me pursue that track, so that's why I joined the faculty at the University of California to study the biochemistry of the secretions of the maggots, as well as try and provide maggots themselves to therapists around the country who were interested in applying it to their own patients.

I have a two-part question for you: The first one is, you mentioned earlier when you first started that you started by isolating maggots that people came in with that were already present on their wounds, right? So the question is, number one: Explain to people, because a lot of our audience may not know exactly what a maggot is. We've all heard of it, we think of it as something disgusting, it's maybe in the garbage, at some point, if you leave garbage out for too long. So what exactly is a maggot? And then the second part of it is: How do they get into people's wounds, naturally? Where does that infestation come from, if that's the right word to use? And then another part of the question is: Is there some empirical or cultural evidence that there are cultures that have been using this kind of therapy naturally for years, hundreds of years or thousands of years. Has this happened in the natural world?

Sure. I hope my brain is able to remember all those questions. Maggots are really the larva stage of the fly. So a butterfly larva would be called a caterpillar, but the fly's larva is called a maggot. My life would be a lot better if we called them caterpillars also. For many species of flies, the adult female will lay her eggs on the host's substrate, whatever the larvae will eat. For certain flies, they feed on dead tissue. Maybe dead organic matter out in nature or out in the garbage can, vegetable matter. For some flies, particularly the blow flies, which is a small group of flies, their larvae feed on animal matter that's dead. Let me rephrase that: For the blow flies, many of their larvae feed on animal matter. And for a few species, only dead animal matter.

So they're nature's recyclers, if you…

Correct. And out in nature, they usually deposit their eggs on a dead body. They detect that dead body by the odors. And sometimes, they can't tell the difference between a dead body and a dead part of a live body. So when they deposit their eggs on a wound or on gangrene of a live vertebrate host, that condition is called myiasis. Maggots living on a live host. I'm trying to remember and segue to your next question, which was?

Well, the second part was, for the people that come in with maggots in their wounds, is it just that they're not caring for the wound? The fly happened to sit on the wound and lay eggs in a relatively short amount of time, I would guess? And then the next part is: Is there any empirical evidence of this kind of therapy being used in cultures in history?

So when a wound is infected or dead and draining, it smells like a dead body. That's why the flies will lay the eggs on it. The larvae will hatch from those eggs, they secrete their digestive enzymes, they don't have teeth, they don't bite off pieces. They basically dissolve the tissue, the dead tissue, by secreting their digestive enzymes, and then suck those juices up. For some species, their digestive enzymes are only capable of dissolving dead tissue, not live tissue. So they are particularly useful from a medical standpoint. That's been observed by some groups, probably for thousands of years. There is evidence that the Mayans did that and that the native people in Australia also used larvae. Not strong evidence, not a lot of evidence, but there are some writings that exist. In Europe and North America, there were some observations, primarily by military surgeons who noted that soldiers fallen in the battlefield with wounds that were infested with maggots actually had much, much better outcomes and survived their wounds, compared to those whose wounds were not infested.

In fact, during the American civil war, confederate soldiers captured by the North and left in Hospitals without dressing changes and without the care that the Northern soldiers were receiving, whose dressings became infested with maggots also did better than the soldiers who got good medical care at that time, which meant clean dressings. So we have that kind of evidence, but it wasn't until a former military surgeon himself, William Baer, who after World War I became the first director of orthopedic surgeons at Johns Hopkins, who intentionally prepared maggots, placed them on children with serious bone infections and demonstrated that maggot therapy was really working.

So if it's a bone infection, they're placing it deep into the wound, into the body.

What William Baer and others after him basically did was remove the infected bone surgically, but there were not good antibiotics. These wounds often succumbed to other infections or they were unsuccessful at removing all of the infection from the bone so they would put the maggots into this deep wound after resecting the dead, infected bone, allowed the maggots to control the remaining infection. They observed that these wounds filled in with healthy, what we call granulation tissue, it's red, rumpy, bumpy tissue filled with good blood vessels, and filled in those wounds much faster than if they had simply cleaned the wound or debrided the wound with the maggots, or worse yet, done nothing at all.

It's interesting because this is such a disconnect for people, talking about this. And I'm sure this is something you bump up against in your work, right? We think about maggots, we think about these things as being dirty. Like, "Oh, keep things clean, keep these off of you." And you're saying that actually, wounds and things in medical situations, when we keep them really clean, sanitize them, use the antibiotics, they actually don't do as well as when we put these things that we think of as being dirty or gross in these wounds, and they miraculously help healthy tissue grow and just get rid of the dead tissue. I think that's a real disconnect for people, isn't it.

It is a disconnect, and I've given a lot of thought as to why that is. First, let me say though, that I don't want to imply that modern techniques of sterility and hygiene are not good. The case I described was in the 1920's, 1930's where we really didn't have the antimicrobials or the understanding of medicine that we do now. But clearly there is a disconnect between our cultural perceptions of maggots and hygiene and that's been an issue that I've had to overcome. It is cross-cultural as well. I've looked into other cultures, and their perception of flies is also often dirty, filth, death-related. That's really because of the context that we come into connection with flies. These flies are on dead bodies, the maggots are feeding on the dead bodies. The dead bodies stink. It's not really the larvae, it's not the maggots that smell bad. It's not the maggots that cause the death, but they are associated with the garbage can, with the dog poop in the backyard or the dead body in the field. So we draw these connections, but they're not the right sequence that death and destruction and infection and rotting came first, and it's actually the maggots that are cleaning it up.

It seems that they're doing a couple of different things, the maggots in the wound. You mentioned earlier that there is some empirical evidence that they've been useful in battle and people with open wounds and so on, so it seems like maybe they're doing two things: They're removing the dead tissue, which is important for the wound healing part, but it seems like they may also may be preventing infections in the wound itself. So they're offering a kind of a layer of protection against opportunistic bacteria that may look to take advantage of an open wound and create an infection.

Research actually shows that they're doing three actions: They are dissolving the dead tissue, they are killing bacteria, I should say microbes, because it's not just bacteria. They've been shown to kill certain harmful fungi and recently shown to actually have antiviral activity as well. But there is a third action that's interested me a lot for years, and that's the growth-stimulating activity of the maggot from an evolutionary standpoint, from a what-makes-sense-about-the-world standpoint. I sort of understand why these creatures that live in dead bodies filled with infection need to be able to feed, and need to be able to protect themselves against all the microbes. I've never really understood the why, about why they would be helping to heal a body that is living when they don't normally live in that context, number one, and how is that to the benefit of the maggots anyway, which will be finished feeding in two days and leave the host? I don't understand why, but I do know that there is lots of clinical evidence in terms of observations and some studies, as well as laboratory evidence that the maggots are doing that function as well.

Maybe that's an accidental function of theirs, right? Maybe that's a co-evolution where our cells respond to the presence of the maggots removing the dead tissue in a way, looking at that as a stimulus to increase the growth of new tissue. But yeah, it's a fascinating area to think about.

I would totally agree with that. I think maybe it's not so much the intent [inaudible 0:17:28.7] with the maggots that's leading to the wound healing, but rather the natural response of the vertebrates, of the humans that follows with healing, not just because it's clean, not just because the bacteria are removed, but maybe in response to the physical stimulation over the wound that we already know causes the release of cytokines, can cause maybe some local electrical stimulation that ultimately, though, results in angiogenesis, in the development of new blood vessels, in the migration of cells faster over the supportive tissue and so forth.

What I love about this part of the conversation is that it really speaks to these unique mutualistic relationships that we develop with various types of organisms throughout the course of human evolution, really. When you study the microbiome as we do quite a bit, you see that, you see that microbes do things for us that seem a little bit altruistic, and you think well, why would the microbe do that? They're not doing it for us. There is some side benefit for them and our system just happens to count on those signals or metabolites or whatever it is that they're producing, to use that for an action. For example, there are microbes that increase your tendency to be more social, right? Why does a bacteria care if you're more social or not? It cares because it wants you to go and spread itself throughout the community, right? But then we've taken those cues to become more social and it stimulates us to act in a certain way. So I think that's absolutely fascinating. Can you talk a little bit about how maggots control bacteria? What are their mechanisms to prevent infections and clean up the space?

As I mentioned, the maggots feed by dissolving the dead tissue and sucking it up. With that dead tissue, that infected dead tissue, they're sucking up a lot of bacteria as well. It's been shown for decades that there is antimicrobial action going on in the gut. By the time the food arrives at the hindgut, all the bacteria have been killed. We still believe that since there is also antimicrobial activity going on in the wound, that these same factors are being secreted along with the digestive proteins, some antimicrobial proteins or biochemicals, let's be more broad there, that are nonetheless still active in the wound, outside the maggot's body and killing bacteria. So now we've got ingestion, we've got antimicrobial killing through these chemicals. What chemicals? At least one has been isolated and characterized to the molecular level. It's related to the [ph 'defensing' 0:20:44.7] group. It's a small protein that's been named Lucifensin that basically punches holes in the bacterial wall. It looks like there may be some other molecules, lipid molecules that also have activity but they have not been characterized in detail yet. So that's yet to come.

Let me get my train of thoughts to answer your question more fully: Clinically, several researchers have been able to describe a decrease in the number of pathogens on the wound as a result of the maggot therapy, as well as a decrease in the population size of those organisms, those species that remain. Some other researchers have looked specifically at antibiotic-resistant organisms such as MRSA, Methicillin-resistant Staphylococcus aureus. And they have been excited and published on the fact that the maggots kill those as well. It's not really such a surprise though because the mechanism of action is very much different from the antibiotics like Methicillin, Penicillin and so forth. It's an entirely different mechanism with this hole-punching, and that explains why they are so effective, even in the multi-resistant bacteria group.

So there are some amazing things that you're talking about in terms of problems that this type of therapy can address, people coming in with wounds that just won't heal, infections that are resistant to antibiotics. So the questions coming to me are: Why is this not more broadly used?

These are some serious problems that we face in hospital and outpatient settings all over. So if this is an effective tool for this, what's the barrier to this being used more widely as a solution?

I don't know exactly what the barrier is, I do have some observations, some theories. Certainly in Europe, maggot therapy is much, much more popular and in greater use. In North America, it's not used as much as I think it should be or could be. What do I mean by that? What's the evidence of that? Diabetes, as you know, results in damage to your immune system, damage to your neuromuscular system, and many people end up with these foot wounds that will not heal. They spread, they become gangrenous and they account for over 100,000 amputations per year in the US alone, just from diabetes. Now when we add pressure ulcers, traumatic wounds and so forth, the wound population, the non-healing, chronic wound population is expansive. But just focusing on these diabetic foot wounds that do not heal and result in amputations, that's over 100,000 a year.

What is the use of maggot therapy in the US? It is — I have to estimate that less than 2% of those patients who are getting amputations are given a trial of maggot therapy. The total use of maggot therapy in the United States is probably somewhere around 2000 patients, 3000 patients a year. Of course not all of those are even diabetics. Probably 50% of those are pressure ulcers, 40-50% another 40% at best are diabetic foot ulcers. Venous stasis ulcers and a wide variety of other wounds are being treated. So less than 2% of those patients that go into amputations are ever given a trial of maggot therapy. What does the published literature from trials and case studies show? In published studies of people with diabetic foot ulcers who have failed all other treatments and are scheduled for amputation but given a course of maggot therapy as a last resort, 50% or more of those patients healed their wounds and avoided amputation. Kaiser Permanente published a study a few years ago where 74% of their patients destined for amputations were given maggots as a last resort, either avoided amputation or were able to have a much more conservative surgical resection rather than the amputation that otherwise would have been done. So I feel that if we are not giving more of these patients, these patients that are getting amputations at least a trial of maggot therapy, we are failing them and failing to help save their limbs. That's one side of the answer to your question, the evidence that it really isn't being used to the full extent that it could. But you were also asking why it is not being used more. I told you that it's used much more commonly in Europe than it is in the United States. There is no substantial difference between diabetic foot ulcers and other wounds in Europeans versus the United States. And having done some of my training in Europe, I can tell you that there is no difference in the capacity, the capability of surgeons in Europe versus those in the US. They're just as well trained. They don't need maggots any more than we need maggots. But there is a big difference in terms of their medical technology reimbursement scheme, shall we call it? And how healthcare finances are designed and spent in Europe versus The United States. In The United States, we are a very procedure-oriented society. You get paid for the procedures that you do. Maggot therapy is not an expensive treatment at all. The cost of a bottle of maggots is somewhere on the order of $250-$300 currently. That's the cost of one tube of a chemical enzyme that also debrides wounds, and the median number of treatments for maggot therapy required to completely clean that wound is 1 2-day treatment. The enzymatic debriding agents generally take 8-12 weeks of use, daily applications and the cost is about $300 per tube, which might last a week. So the cost of supplies and nursing time is much greater, and yet that is reimbursed by insurance companies and reimbursement is more difficult to obtain for maggots. So what a lot of doctors tell me is that it sounds good, it looks good, but they can't survive doing maggot therapy and not getting paid for it.

You know, what's interesting with what you talk about with the diabetic wound care, as I understand, one of the big problems with the diabetics, and why their wounds, especially on the feet don't heal, is because the capillaries and the micro vessels really aren't supplying blood anymore to that area because of the diabetes itself, right? You mentioned the word Angiogenesis before. The fact that the maggots have the capability of healing the diabetic wound better than other techniques do, and the angiogenesis is present, is it also true then that the maggots are not only of course healing the wound, but then bringing about new blood supply to that part of the limb that wasn't there before?

I believe that's correct. I believe that one of the reasons that maggot therapy is successful at saving limbs that otherwise are felt, because of poor blood supply, to have no likely successive healing and therefore, they are scheduled for amputation is because of the improved oxygenation, the new vasculature that the maggots can bring to that. That was actually part of a clinical trial that I had intended to conduct a few years ago, but for various reasons, it was not funded.

That's amazing when you think about it, because to me, what that means is that it also would reduce their risk for further wounds if they brought about new vascularization to that part of the limb. That makes it a functional limb at that point.

Indeed if the improved vasculature were to cover the whole area, that would be very true. We know that vasculature and oxygenation is increased locally, and we know that its effects last longer than the treatment itself, because that's been measured by a group in Germany. We don't know to what degree of the total limb that effect pertains. There's lots of research that still needs to be done in that regard.

I thought we'd broaden out a little bit and just have you talk a bit about the bigger picture of what you call biotherapy, biotherapeutic things, because maggots are a piece of that, and that's certainly your speciality area, but you have a broader interest in biotherapy in general, which goes beyond the maggots, right? Can you talk a bit about what that is?

What we call biotherapy is the use of live animals therapeutically. That may have started with leeches and bee venom and maggots, some of the older therapies, but then we realized that service animals, guide dogs have been used for years and years and it's well accepted as medical treatment. Then we opened our eyes even further and recognized that microbes are clearly an excellent example of living organisms. Maybe not animals in the classical sense, but living organisms nonetheless that can lead to healthier lives or actually fewer illnesses. These would include the bacteria, for example, but also the viruses that are parasites of pathologic bacteriophage. Now the field really includes all of those things.

From the entomology standpoint, beyond maggots, what else is really exciting for you in terms of biotherapeutics?

I am not looking at any other insects at this time, in terms of biotherapeutics. In the past, some other insects have been used therapeutically, probably the best-accepted one would be the mosquito which transmits malaria, and with that you have high fevers, which used to be one of the few things that would kill syphilis. So malaria therapy, initially administered through infected mosquitos, but altered administered through a syringe was actually a well-accepted treatment for syphilis 100 years ago.

That's fascinating. I want to understand a little bit more about how the maggot therapy works, right? You said it's a two-day therapy, so you've got a possibly infected, but certainly an open wound, a fresh wound, and then you're essentially taking about a bottle of those maggots and pouring them into the wound. You'll make it a little more elegant when you start to answer, and then the maggots feed and do what they do for a couple of days. At the end of those couple of days, are you going in and removing the maggots? Are they turning into flies and flying away out of the wound? How does this happen?

So what are the logistics, right? For maggot therapy. Let me first describe the lifecycle of the maggots and the flies to put into context what we do and why we do it. The female fly lays eggs, her eggs hatch, depending on species in maybe 12 hours. They immediately start to feed, and they'll feed for 3-4 days depending on conditions like temperature, the abundance of food, the type of food. Concerning the species of maggots that we use medicinally now, once they are finished feeding, their natural instinct is to leave the host. If they were out on a cadaver and continued to do what they do right there, the next scavenger to come along would eat what remains of the carcass and the maggots. If there were any maggots like that, they're long extinct. The blow flies that we work with are naturally, instinctively motivated to get as far away from that host, that carcass, as possible. Hide under a rock, under some dirt, whatever, because they are going to pupate, they're going to make like a cocoon, for a week or two before they turn into, metamorphose into a fly, an adult fly.

So the actual larvae stage, the maggot itself is moving.

Correct.

And how does the maggot move? >

The maggot crawls, like a worm by contracting and extending itself as it moves along, and it has some little tiny spines, little tiny sharp thingies, [inaudible 0:37:06.1], let's call them, in rings around its body, plus it has no teeth, but two modified mandibles that stick out forwards from its mouth, which are used like a mountain climber's little pick-axe, little hammer axe thing. So the maggot puts its mouth hooks onto the ground or onto the substrate and pulls itself forwards. They spend all of their time on the cadaver or on the wound during feeding, but then they will crawl away in that fashion out of the wound. I should add that we understand both the mouth hooks and these spines, as the maggot crawls about the wound, are actually doing a lot of the debriding work, the dislodging of the necrotic tissue and debris. That is one of the factors that the FDA used to justify the classification of maggots as a medical device and not a drug, even though the maggots are also secreting proteolytic enzymes.

So back to the lifecycle and logistics of maggot therapy, I tell people that getting the maggots out of the wound is not a problem. They are self-extracting. They will come out of the wound on their own. What we need to focus on is how to keep them there until the therapist is ready to remove them all at the same time, and not having come out willy nilly on their own. So there are two basic methods right now of maggot dressings to accomplish that: The long time conventional method was to apply the maggots directly to the wound bed and cover them with a porous net fabric that allows air to get to the maggots, the dissolving tissue and infection to drain out of the wound so that the maggots don't suffocate and they don't drown. And they remove that in two or three days. There is another method that was recently developed where the maggots are supplied in a net bag so that they are completely contained. We called that contained or bagged maggots. That bag of maggots can be placed on the wound. Their secretions will get out. They don't have the same physical action on the wound, they can not get to all the nooks and crannies because they're stuck in the bag. So the treatment lasts a little longer, it is a little less effective, it is a little less efficient, it is a little more costly, but it has still been shown to be as or more effective than the treatments that are more conventional, the non-maggot treatments. Studies still show that it's very effective. A lot of therapists actually prefer to handle the maggots in the bag, what the germans call "Maggot Ravioli'' rather than what we call free range maggot therapy. The way my lab provides therapy is to impregnate gauze with the maggots so that when you apply free range maggots to the wound bed, you don't have to pour the maggots out of a bottle. You don't have to count maggots to get the right dose. The dosage is 5-10 mangos per square centimeter of wound. All you need to do is transfer the gauze pad, open it up and that is the predetermined concentration of the maggots for that wound size.

Fascinating. Another problem with wounds, obviously, is the pain associated with them. Is there any sort of analgesic effect from the maggots doing what they do, a pain-reducing effect?

There is no direct and immediate pain-reducing effect of the maggots. Most people have no wound pain and do not feel the maggots, because their nerves are damaged or destroyed. In those patients who have wound pain, the maggots can be felt after about 24 hours, and that crawling over the wound would stimulate these noxious stimuli, these damaged wound endings are going to cause them some discomfort or maybe frank pain. So I tell therapists not to tell their patients that the maggot therapy is painless. It's not painless if they have pain. But those patients who have pain, warn them that they may feel pain, give liberal access to whatever analgesics will be necessary during that time, and I always let my patients know that when their pain is not controlled, I will gladly remove the maggots immediately, the pain is not due to any damage. The maggots don't bite at the wound. They're simply crawling over damaged nerves, so as soon as we take them out, the pain ceases immediately. What is interesting and not a direct answer to your question, but very relevant is that the wound pain that patients who have pain had been having is often, I would say usually much, much less after the treatment is finished. It appears that some of that wound pain is probably due to the microbes, the pathologic microbes and their secretions, or the body's secretions of lysozyme and all the other antimicrobial molecules that we ourselves are producing through the release of our white blood cells. And all of that can now subside. The infection is gone and the painful wounds that I have treated in many others are no longer painful.

Fascinating.

It's incredible information. And I know you have a foundation that you've started to provide training information to anyone who is interested, to professionals who are interested. Can you tell us just a little bit about the foundation, the things that you do there?

Sure. The Biotherapeutics Education and Research Foundation, or The BTER Foundation, as we call it, was established in 2003, initially to provide information to patients and therapists so that they would know what kinds of modalities are available and what can be done. We are also interested in making sure that therapists are adequately trained so that they don't just grab some maggots from wherever and put them on and not really understanding how to make this most effective and most comfortable for the patients. We also do research in-house, as well as support research wherever we can, or the publication of research to get more information and a better understanding of all of the biotherapeutic modalities. We focus primarily on the treatments that don't have other organizations already supporting them. So for example, we don't do anything at all for guide dogs. That's well-established, there are organizations much larger and more financially stable able to help all of the cute animals. Most of our focus has been on the orphaned animals, if I could call them, the maggots and the leeches and the bee venom and so forth.

They're not so cute.

They're not so cute.

Yeah, so if somebody listening has a diabetic wound or knows somebody, a family member with it and from listening to this, they become interested in "Hey, I want to electively choose to try to get some maggot therapy in my wound", what's the best place for them to go?

They can certainly come to the website for our foundation. bterfoundation.org.

And they can find resources for where to get this kind of therapy as well.

Correct.

Yeah, the website is a wealth of information I highly recommend for those of you who are listening, who are interested in learning more to go check that out. You've got such great information there, and we really appreciate you spending the time with us today, this has been a fascinating conversation right up our alley, so we very much appreciate your time, thank you for being here.

Thank you.

And thanks to all of you for joining us for today's episode of The Better Biome Podcast. Tune in next week to continue with us as we journey through the universe within.