IRA FLATOW, host:
You're listening to TALK OF THE NATION/SCIENCE FRIDAY. I am Ira Flatow.
You know, if you've been swimming in your favorite lake this summer, I'm willing to bet that at some point you or members of your family came out of the water with a few unwelcomed guests hanging on. I'm talking about leeches. It certainly has happened to me. Leeches, despite their reputation, have been used for centuries for medical, medicinal purposes. You know, we've seen them in pictures, you know, on TV and in old movies with medieval doctors. Well, for the last 30 years, leeches have been making a comeback in medicine. The Food and Drug Administration now classifies them as medical devices and has approved them for use in microsurgery. And just yesterday the agency began discussing how to regulate the breeding, transport and sale of leeches.
This hour we're going to talk about why leeches are not just for beaches, why surgeons routinely use them now, and why a hospital in New York, Beth Israel Medical Center, will this October become one of the first American hospitals to offer leech therapy for osteoarthritis of the knee. Leeches treating arthritis. What's the connection? Well, it turns out that leeches may actually secrete morphine, a potent painkiller. We're going to talk about this morphine-leech connection.
Let me introduce my guests. Dr. Woodson Merrell; he's the founding executive director of Beth Israel's Continuum Center of Health and Healing. He's also assistant clinical professor of medicine at Columbia University's College of Physicians and Surgeons here in New York, and he's on the phone with us.
Welcome to SCIENCE FRIDAY.
Dr. WOODSON MERRELL (Beth Israel's Continuum Center of Health and Healing): Thank you. Nice to be here.
FLATOW: You're welcome. My second guest is Dr. George Stefano. He's director of the Neuroscience Research Institute at the State University of New York College at Old Westbury on Long Island. And he has found that some animals, including humans, produce morphine, one of the strongest natural painkillers, and he's now looking at these leeches and how they do what they do. And Dr. Stefano joins me by phone from his home on Long Island.
Welcome to SCIENCE FRIDAY.
Dr. GEORGE STEFANO (Neuroscience Research Institute, SUNY College): Thank you very much. Pleasure to be here.
FLATOW: You're welcome. Dr. Merrell, were you always interested in leeches?
Dr. MERRELL: No, actually I was never interested in leeches really till this article came out in the Annals of Internal Medicine back in November of '03. Up until that point I, like most people probably did and probably still do, think of leeches as kind of a discredited tool that had been used, you know, centuries ago and was not aware of its use in microsurgery. And then this article back in November a year and a half ago really awakened me to the possibility of using leeches. And as I've begun to investigate in the last year, it became clear that they have a real possibility not just in microvascular surgery but inflammatory conditions and particularly starting with arthritis.
FLATOW: Let's talk about what we know how they work in microsurgery. What does a leech do for you in microsurgery?
Dr. MERRELL: It does three things. It secretes particularly an anesthetic substance that actually numbs it, and most powerfully it actually secretes an anticoagulant that prevents blood from pooling in the veins of surgery, and it's been used for about 30 years for that very successfully. Many grafts actually will not make it without leech therapy.
FLATOW: And so are they now just regularly used in the hospitals everywhere?
Dr. MERRELL: No, not regularly at all. There are a few vascular surgeons, plastic surgeons; they're talked a lot about within the field mainly of plastic surgery, and it's probably a minority of plastic surgeons who will use them.
FLATOW: Have you always been open to alternative therapies like this?
Dr. MERRELL: Very much. I was actually raised with homeopathy and after I finished medical school at Columbia and residency, I went back to my roots and began training in these disciplines: acupuncture, herbal medicine, nutritional therapies. We're really at the state now where it's called integrated medicine, where conventional medicine is recognized and that many of these therapies, formerly considered alternative, actually have enough evidence basis to begin incorporating into conventional medical practice.
FLATOW: Now how--what is the leech connection to osteoarthritis? Why are you going to be using this come this fall?
Dr. MERRELL: It's the result of two studies. The first one was done in an arthritis journal. It was really not that well-designed, but it was suggestive, and the second study was actually a randomized controlled study done with 50 patients at a clinic in Germany--very well-done study--showed clearly that the leeches--there were just four leeches placed around the knee. One treatment; significantly reduced pain more than the control, which is an anti-inflammatory patch that was put on for a week. There was significantly better pain control with the leeches, and over the course of actually three months in terms of functional ability, range of motion, mobility, the leeches therapy was much better than the conventional.
FLATOW: And what do you attribute that to?
Dr. MERRELL: Well, we really don't know. Dr. Stefano's work is trying to elucidate clearly anesthetic properties, the analgesic properties. It's not through anticoagulant properties; clearly it's an anti-inflammatory substances one of which we know is hyaluronidase, which may actually allow deeper tissue penetration of some of the substances that allow reduction of inflammation of the joint, but that really is a guess because we really don't know. There are hundreds--probably over a hundred, probably, peptides in the saliva of leeches that are just beginning to be elucidated, so there's a lot of work to figure out the mechanism.
FLATOW: Now, Dr. Stefano, you've been studying morphine produced by animals, which we don't normally think animals produce morphine.
Dr. STEFANO: Exactly.
FLATOW: Do you think that the leeches are making morphine here?
Dr. STEFANO: Well, right now just from the studies that we've performed, we know that the leeches contain morphine. But if you put this field in the perspective with a morphine view or an overriding envelope, what you have is that morphine is one of the oldest medicinal compounds that humans have used; it goes back thousands of years.
FLATOW: So we don't normally think that animals make morphine.
Dr. STEFANO: No, we don't, but what we're finding out today is that indeed they do, and they can produce it at very low levels. As a result in the past, given the technology it's been very hard to detect. But what you can do in trauma and things associated with trauma is that all of a sudden the endogenous morphine levels increase dramatically, and this happens in invertebrates, you know, such as the leech. We use mussels routinely in our lab. We've also--what really makes the story extremely credible, years ago we cloned an opiate receptive--that's like a lock mechanism that looks for morphine as the key--we cloned this receptor and it only responds to morphine. It does not respond to opioid peptides like metenkephalin, betaendorphine, so what we think is we have this entire new signaling family. We do we find this receptor? So far we found it on neural tissues. We found it on immune tissues. We found it on vascular tissues. And what is it doing? It's doing the same thing that worries people with substance abuse. It downregulates these tissue's ability to become excitatory and to respond.
Now take that little blurb of information that covers 87 papers that I've written on it and other people have written--now you put this in perspective of what this little animal is using, and now you have a molecule that not only numbs the individually locally, and that's just want you want--locally; you don't want to numb the whole organism. You want to numb them locally and at the same time downregulate the immune response. So morphine coming from a leech--if we can demonstrate that--morphine coming from a leech is a perfect way to achieve a great meal for the leech because it's doing what morphine normally does. It downregulates tissues. And morphine, by way of this receptor that we've cloned called a mu3 receptor--Patrick Cadet in my lab did that--what we've done is demonstration--would you believe--as a result of hitting this receptor, it releases nitric oxide, a well-known vasodilator compound. So by the leech killing the sensation of pain, it creates an environment to take its own meal in. So a leech is working on the host basically by communicating with the host's already existing system.
FLATOW: So 1 (800) 989-8255 is our number. So you're saying that since the receptors are built into our bodies, we must have some reason to have them there.
Dr. STEFANO: Right, and we're making endogenous morphine.
FLATOW: Do you think we ourself are making it?
Dr. STEFANO: Absolutely.
FLATOW: And where would we find--I mean, what part of the body would be making it?
Dr. STEFANO: Right now we have those papers in review.
Dr. STEFANO: I would love to say more, but you know, scientists are very cautious people.
FLATOW: We only like those kind of scientists.
Dr. STEFANO: OK. Well, you have one on the phone, that's for sure.
FLATOW: Well, let me get to the part--critics of yours have said, you know, that your experiments are faulty about the morphine in the leeches, that maybe there's morphine in the food that you're feeding the leeches.
Dr. STEFANO: We don't feed the leeches food. We get the leeches from Leeches USA, and when we absolutely clean and wash the animals completely and Leeches USA doesn't even feed them. So when we get the animals, they're clean, they're washed; we take every precaution to make sure there's no contamination in the instruments, no contamination in the columns we use to extract and to look for this material. We take a whole slew of what we call safety measures and controls to make sure that this isn't coming from somewhere else. Right now we can say that the leech contains morphine. We do not know at this moment if the leech has the ability to make it. And that's what we're testing.
FLATOW: Where would it get the morphine from then?
Dr. STEFANO: Well, usually leeches have a first blood meal. So it'd be an equally interesting story if the leech in its first blood meal when it's a small organism can get this blood and then conserve and somehow store morphine. There's a number of hypotheses than can, you know, fall into this category, and again, I'm just being cautious at this time.
Dr. STEFANO: Because all we did was find it in the animal.
FLATOW: Right. Dr. Merrell, when you do your leech therapy on the knees of your arthritis patients, how do they react when you tell them you want to put leeches on their knees?
Dr. MERRELL: Well, now we're going to begin this in October. We're actually putting the protocols together now, and we're recruiting patients and we'll begin our first patients as a pilot clinical use in October, probably the first 20 or so. Then from that point, we'd like to actually do a formal study. Right now Dr. Dobos and some of the group from Germany are applying to the NIH to have a multicentered trial that we hope to be a part of, so we want to get our clinical experience going to get a feel for, first of all, can we duplicate his result? Will we find that it works as well as that study showed?
FLATOW: Well, but you're going to have patients to try it out on, right?
Dr. MERRELL: Abso--we have more patients that we can treat right now, so we're developing the criteria in terms of who we shouldn't treat. For example, people with bleeding disorders should clearly not have leeches put on them. Sometimes there's an oozing of blood; people with anemia. So we'll actually develop criteria in terms of who should be excluded and who we're going to treat at the beginning.
FLATOW: 1 (800) 989-8255. Let's see if we can get a call or two in here. Let's get Jerry from Ft. Myers, Florida. Hi, Jerry.
JERRY (Caller): Hi. Thanks for taking my call. I was wondering if blood-borne pathogens are an issue with this treatment.
Dr. MERRELL: Yeah, that's a very important point, and I think that all plastic surgeons pretreat just like dentists will do for people with heart murmurs with antibiotic before and after dental procedures. Aeromonas is a bacteria that seems to be a normal inhabitant of the saliva of the digestive system of the leeches, as humans have hundreds of species of bacteria in their system and mouth as well. So this organism can produce a local infection and we're going to at the beginning probably going to have to treat every patient with a couple doses before and after of an antibiotic just for one day, a one-day course to protect against this. Seems to be difficult, and I don't know if Dr. Stefano has found this to eliminate, completely sterilize the leech to remove all signs of bacteria within them.
FLATOW: Let me remind everybody that this is TALK OF THE NATION/SCIENCE FRIDAY from NPR News. Talking about leeches this hour with Dr. Woodson Merrell and Dr. George Stefano.
Do you want to respond to that, Dr. Stefano? Is it hard to clean them out so there's nothing--no pathogens in there?
Dr. STEFANO: Well, there maintained in an extremely sterile environment, so that usually minimizes it, and I think Michel Salzet in France at the University of Lille--he's demonstrated that these animals actually produce a whole slew of antibacterial compounds.
Dr. MERRELL: Right.
FLATOW: Willie in Sacramento, welcome to SCIENCE FRIDAY.
WILLIE (Caller): Hi, Ira. Great show. That's for the opportunity. I actually have personal experience with leeches. In fact, in February of this year I had a microsurgery where they took a pedicle from my forearm and they transplanted it right on top of my Achilles tendon, and what happened was that my foot--what I called--got a congestive ankle failure where there was so much excessive blood that nothing could basically undo the congestion, and what they did was they actually flew these leeches from New York City that was bred for this purpose, and my reconstructive surgeon actually put 18 leeches on my--around my ankle area, and in fact, the leeches were the only reason that I actually saved what they call the flat, and it was just an amazing, amazing feat of what these little critters could do. So I really have a renewed sense of appreciation for them, and I think the doctors know much more about this.
Dr. MERRELL: I'd like to just comment on one thing. The caller points out the fact that they used quite a few leeches for this, and often for microsurgery they actually replace them, and for up to two days after they'll continue to use leeches because they really fill up; between five and 45 minutes they'll engorge with blood and that's it for them and they'll need new leeches. But in the study on arthritis it was just one application of four leeches, and that was it, and the effect lasts up to three months.
FLATOW: Three months for one application.
Dr. MERRELL: That's correct, and we really don't know the mechanisms for this, and some of what Dr. Stefano was mentioning I think is very important and maybe that their indirect mechanisms where there's up and down regulation in parts of the inflammatory system that allow the knee to be healed or it may be actually direct penetration of some substances into the joint. We're really not clear on that.
FLATOW: Could this be--I'm sorry. Go ahead.
Dr. STEFANO: Morphine sounds like the good candidate. We just published a paper in Medical Science Monitor where we ran the entire human generae(ph) on the microchip, and would you believe morphine downregulates all the pro-inflammatory-type signals? It's an amazing molecule.
FLATOW: Could any kind of arthritis--now you're working on one kind, right? Could other types of arthritis be, you know, treatable by this?
Dr. MERRELL: The article is done mainly on osteo, but we're looking at other kinds such as rheumatoid arthritis, psoriatic arthritis and more autoimmune arthritises that are more severe to see; those should be amenable to the treatment also. First, we're going to do the osteoarthritis and replicate the study that was done in Germany, but we look forward to expanding it to other forms of arthritis.
FLATOW: What about other inflammatory diseases? I mean, if you're basically--you know, I'm just guessing. Would that be amenable too?
Dr. MERRELL: It's--theoretically yes. I've not seen any research of anyone looking into that, nor anecdotal reports of people getting leeches where that was the case, although it historically has been used for that, which is why they did the study in the first place for arthritis. I think that for some of the mechanisms that Dr. Stefano's mentioning and some of the other anti-inflammatory substances that may exist within the saliva of the leech, it makes sense that it may have other inflammatory conditions, though at the moment there's not enough evidence to make a conclusion about that. It's certainly an exciting area of investigation.
Dr. STEFANO: Absolutely.
FLATOW: And how many animals do you think, Dr. Stefano, give off morphine or have morphine that they can exchange?
Dr. STEFANO: Well, so far the ones--I mean, if you are asking me individually?
Dr. STEFANO: I mean, so far the ones we've tested--they all have it.
FLATOW: All animals.
Dr. STEFANO: We've never found--let's put it this way. We've never found a leech that didn't have morphine.
FLATOW: What about other kinds of animals that might be of the same class?
Dr. STEFANO: Well, in other parasites...
Dr. STEFANO: ...we've done work with Greg Fricchione up at Harvard, and Bill Secor at CDC, and we found it in Dracunculus medinensis--this is a human parasite. It also appears to contain morphine. We've done it with Ascaris suum; that's a pig parasite in the intestine. It also appears to produce morphine. And with another parasite: Schistosoma mansoni also appears...
Dr. STEFANO: ...to produce morphine.
FLATOW: This is quite interesting. We're going to have to be following this with you gentlemen. I want to thank you both for taking time to talk with us.
Dr. MERRELL: Thank you.
Dr. STEFANO: Thank you.
FLATOW: George Stefano, director of Neuroscience Research Institute, State University of New York College at Old Westbury on Long Island. Dr. Woodson Merrell, founding executive director of Continuum Center of Healing and Health at Beth Israel Medical Center in New York.
FLATOW: And if you missed anything, surf over to our Web site at sciencefriday.com. You can podcast our SCIENCE FRIDAY broadcasts here, take them with you. Have a great weekend.
We'll see you next week. I'm Ira Flatow in New York.
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