 Welcome to Think Tech on Spectromosi 16, Hawaii's weekly newscast on things that matter to tech and to Hawaii. I'm Cynthia Sinclair. And I'm Anna Jimenez-McMillan. In our show this time, we'll visit the April meeting of the Honolulu Science Cafe at Hasser Bistro for a talk about research on box jellyfish. The speaker was Dr. Angel Yanagihara of the Pacific Biosciences Research Center at UH Minoa. She called her talk the science of the steam. The Honolulu Science Cafe, there are many science cafes around the world, recently met downtown for a special talk by Dr. Yanagihara, one of the foremost researchers on box jellyfish. These are known in science as cubozoans. Cubozoans, of which some 50 species are found in tropical and temperate oceans around the world, are fatal. They take their name from their cubic body, which has long tentacles growing from the four corners. The tentacles have thousands of specialized cells that fire microscopic harpoons at more than 60 kilometers an hour. The harpoons carry spiny tubes that inject the venom. Tropical box jellyfish stings kill more people every year than sharks. Current estimates are about 500 deaths per year, but many others go unreported. 90% of these deaths are among young children in rural Filipino fishing villages. Dr. Yanagihara has traveled to these villages to study these incidents and help people deal with them. Dr. Yanagihara was born in Alaska and obtained her undergraduate degree at the University of Virginia and her PhD at UH for research on cellular ion channels. Her work on box jellyfish was triggered by a near fatal sting she experienced in an attack by a swarm of box jellyfish in Waikiki. That happened in 1997. The year she took her PhD, box jellyfish almost killed her. Now she wants to save others from their venom. She is now the director of the Pacific Nadaria Research Laboratory and an associate research professor with joint appointments at the UH Pacific Biosciences Research Center, the School of Ocean and Earth Science and Technology, SOEST, and the Department of Tropical Medicine at the John A. Byrne School of Medicine at UH, Jabsum. Dr. Yanagihara studies the biochemistry and the pathophysiological effects of the venom that box jellyfish inject into their victims. She has developed patented products, a spray and a cream under the name Sting No More to counter the venom. She is famous and considered one of the world's foremost experts on jellyfish. She was chosen as a Fulbright specialist to conduct her research in Thailand last summer and her work was the subject of a recent article in the prestigious journal Science. Her work is not without some controversy, however. Her unified field theory holds that box jellyfish venom contains proteins, including one called porin that puncture red blood cells and release potassium, disrupting the electrical rhythms of the heart. Her findings and the treatments she has based on them are the result of 20 years of research that her colleagues praise as thorough and imaginative. Among the five research groups in the world that study this subject, however, there are some that say other compounds in the venom are the real killers. Dr. Yanagihara acknowledges that jellyfish venom contain other toxins, including molecules that break down lipids and proteins, but her studies show that porins are the main and fastest killer. Resolving the debate will require more research on venom pathology and treatment plus funding, which would be easier to get if researchers could develop more accurate reports on the worldwide number of stings and deaths from these dangerous animals. Dr. Yanagihara is not unknown to think tech. We visited her at UH Minoa a couple of years ago where she gave us a tour of her laboratory and showed us her venom experiments firsthand. It was the kind of place where you would want to be really careful on what you touched. We have basically everything in this laboratory to go from keeping a live marine animal for a few days to purifying the venom, to doing the bioassays, to preparing potential inhibitors and treatments that can be tested for the ability to treat stings. This week we were doing some experiments with live animal tentacles and we tested some of the common things that are out there, the effect of shaving cream, hot packs and cold packs, as well as our own technology again. Here are tentacles in seawater and they're still alive. You see how they're pink? If you put them on your arm, you would be stung instantly. Yeah, this is blood agarose and these clear zones are where the venom has been injected and is slicing the red blood cells and that's why it's clear. If we take another piece of tentacle for instance, this one, and we lay it back on the blood agarose again, you can see right now it's contacting. If we go look under the microscope, you'll see that the niaday are discharging and after five minutes we will remove the tentacle and we do different treatment. So we see if our treatment reduced hemolysis or increased hemolysis and some of our treatments massively reduce hemolysis and some things make no difference or even make it worse. So this is a method that we invented. So it's a novel contribution on our part to the field. Part of the problem in this field is that there aren't enough studies, there are enough labs doing it and it has historically required human volunteers. So there's where the tentacle was. So you see that streak there? This other one to the right was in the incubator for five hours. Where I laid the tentacle, there's a track of the tiny stinging capsules. They're left stuck on the surface. Each of these tiny niaday are filled with the venom. So whenever a tentacle contacts your skin, many, many undischarged niaday are left there. So the red blood cells are having holes pierced in them. The hemoglobin's seeping out and so there's a clear zone. So you can see both where the niaday were left on the algorose, just physically left there as well as the clear zone of the activity. This assay looks at one particular one which we find to be the worst offender and to be necessary and sufficient for causing death in a mouse or in a piglet and presumably in the human being. So that's why our technologies have all been dedicated towards inhibiting this particular activity. In any event, here is the footage we took of her most interesting talk at the Science Cafe. The specialized structure that defines the phylum, Nidaria, are niaday. And this little graphic animation shows what's been reported to be the fastest known cellular biological event which is the discharge of the penetrant niaday called nematocysts. And these tiny microscopic capsules will discharge at bullet speed and bullet force a hollow tubule which basically acts like a hypodermic needle and these are hundreds to thousands of these per linear centimeter of contact with the tentacle. So one doesn't have a venom that is just topically applied but is forcibly injected. And in some cases up to a millimeter or deeper into the skin. Within the phylum Nidaria, there are a number of different classes. Tonight we're going to talk about class cubozoa and cubo you readily would see box. So these animals all have a box like body shape. They don't have the radial symmetry that you might be used to thinking about with jellyfish, the moon jellies, et cetera. So they have four corners and from each corner is what's called a pedalia. And then from that is one tentacle in the case of the crudities and up to 15 tentacles in the chirodropids. These particular families then all together comprise about 40 different species of box jellyfish. Not all of which are lethal stingers. And in Hawaii we are fortunate that our main problem if you will is this alatina, alata in the alatina date. And that animal has the four corners and one tentacle. And reviewing over 20 years of case stories I think that one could potentially attribute deaths of three individuals over that period of time. But it's nothing like the deaths of the notorious chirodropids. From the standpoint of impacts this shows you the number of these cubozoa in various parts of the world. You can readily see that they're mostly tropical and subtropical. But the Caribbean, US and between Mexico and South America has quite a diverse number of species of cubozoa. In Hawaii we have three to four arguably. And then you see the most intense distribution of biodiversity of cubozoa in this Indo-Pacific region. Within the US waters Puerto Rico is also afflicted with various cryptidids. This is a stings of a young woman who contacted me after a horrible case of mismanagement. And this really pointed me early on into the importance of eventually addressing first aid. These hotspots in red are over 20 deaths. And when I first began to look into this I thought it was probably about equally distributed between the Philippines, Thailand and that the reports of deaths in Australia actually having visited Australia many times now one sees wonderful public health outreach. So there's beautiful signs in Darwin in all of the affected areas. You go to the beach and there's a glorious 10 foot tall sign with robust Australians wearing their stinger suits from head to toe and telling you the picture of the box jellyfish and then they have a vinegar pole stocked to the max with full bottles of vinegar. So basically they are way ahead of the curve as far as public health information, outreach, education and just changing the culture. The real tragedies seem to be in the Philippines and each of these numbers represents at least 12 deaths. So unfortunately with the complete maritime culture and the fact that most of these areas that are heavily impacted by this chirodropid the most lethal family of jellyfish are marginalized what they call fisherfolk. So over 7,000 islands comprise the Philippines and in these coastal zones many of these places are cashless societies where there is essentially no income and they're bartering, et cetera. So you can imagine then access to modern care even if it were possible to save lives would be futile. So when we went out to visit the sites of some of these deaths it became readily apparent to me that the heavy lift here was going to be in the public health outreach and educations and this is a story that you might have seen just last year it's a child whose mother is Filipina and she was growing up in Italy and had just won a junior Olympic swimming competition and went home with her mother for a holiday and she ended up being stung by a box jellyfish. The boat handler advised first aid. The first aid that he used was gasoline. So he poured the gasoline on the child and the child died. When we've interviewed again over 600 fisherfolk and other barangay workers, gasoline is one of the common answers and how this has become sort of ossified in the public domain is you can imagine if you're a fisherman off at sea what do you have? Not very much but hopefully you do have enough gasoline to get home but you can imagine the level of pain that a box jellyfish sting would cause you that you would think to use gasoline. So an adult man who gets stung and is desperate for some remedy, trying gasoline, if they happen to survive the gasoline they attribute the survival to the gasoline. So this is the lack of evidence based first aid. The same sort of thing we see with the Friends television show about urine. So people got stung at the beach in New Jersey, they recommended to each other that somebody needed to urinate on the person so they did so and the person got better. So then they attributed that to the application of urine. Is there any evidence for that? Is it helpful or harmful? So we went and developed assays that were models of tissue, human tissue that we could sting and then apply various first aids including urine and gasoline, et cetera. Our efforts at the bench are to do rigorous science to have statistically powered, well designed experiments. We spend years doing, then we can bring that data to the public and we can provide some information that could lessen human suffering and deaths. Coming back to our interviews of coastal folks, we ask them how confident do they feel in treating box jelly stings? And you can see the honesty here. There's basically 85% were either very uncertain or had no idea. The most certain group we found were the men, the fishermen, and they were about 50% confident that gasoline was your go-to answer. But amongst the coastal health workers, 85% were very uncertain. And so this really showed us the need for our work in this field. So I invested the last four years on this topic to do first aid research basically using both a tissue model and an animal model and human case retrospective studies to really dig in deeply and to be able to publish rigorous results. The most common area for stings is basically right offshore of these areas, the ponds. And this is where I go to collect the jellyfish. And this is a beam of the Kapahulu groin out at the 300 foot drop. I'm at the surface and here's one of these animals coming up. You see it's glistening white because it's filled with gametes. It's either a male or a female. So they're coming in purposefully to spawn. They're very strong swimmers. They're not just floating. It's not being driven by a current. They're actually swimming against the current. We scuba divers were out there and we got dragged diamond head. But we couldn't keep up with the box jelly. So they're really strong swimmers. So the take away lesson then if you had to run out the door right now would be to rinse the tentacles off with vinegar and then soak the limb in hot water. 45 minutes actually is even better. And that applies to all of these. It's interesting that biochemically these venoms are very heat sensitive. So it's not the same as boiling. You don't have to be in scalding water. It doesn't take very high heat. They're nowhere as heat resistant as our human proteins are. So we can use that to our advantage. All the marine proteins that ever been looked at in all of the venomous fishes, et cetera all have been shown to be effectively reduced in their activity by hot water. So this is a really remarkable attribute about them as well. And actually it kind of harkens back to the Hawaiian moon calendar. Because during that Kaloa phase one isn't supposed to be out at night in the ocean. Exactly. And that is when they come up. So that's their trigger to come to the shore to spawn once a month. Exactly. Within the geological time and animal life on the planet because they were king of the hill for so long they basically had to outdo one another for the venom. They overshot the mark. There is no animal that is resistant. One could say though, for instance turtles because of the thickness of their esophagus, et cetera alimentary canals, they are capable of ingesting even the most lethal of the bokshelly. But the venom itself is cytolitic on all animals. It's interesting because we've reared some in the lab just to see how many days things take. And when they get to a certain point on the little tentacle arms they have a couple of nigh day. And then when they release and it's juvenile medusae then they do have the same authentic nigh day that we find in the adults. And part of the sea lice phenomenon could be the sudden circulation of the juvenile medusae. Sensitivity and allergy these are things that get bandied about. But actually it isn't anything like beastings where one can be sensitive or have an allergic reaction. Having said that, the dose it's a dose dependent outcome. And for those who have thinner skin children and elderly women and children they're more at risk but I wouldn't use the word necessarily sensitive. Want to know more about Dr. Yanagihara and her work on bokshellyfish and their deadly venom? See pbrc.hawaii.edu Want to know more about her anti-venom products? See stingnomore.com And now let's check out our ThinkTech schedule of events going forward. ThinkTech broadcasts talk shows live on the internet from 10 a.m. to 5 p.m. on weekdays. Then we broadcast our earlier shows all night long and on the weekends. And some people listen to them all night long and on the weekends. If you missed a show or if you want to replay or share any of our shows they're all archived on demand on thinktickawaii.com and YouTube. For our audio stream go to thinktickawaii.com slash audio and we post all our shows as podcasts on iTunes. 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Remember you can watch ThinkTech on Spectrum OC16 several times every week. Can't get enough of it just like Anna does. For additional times check out oc16.tv. For lots more ThinkTech videos and for underwriting and sponsorship opportunities on ThinkTech visit thinktechhi.com. Be a guest or a host, a producer or an intern and help us reach and have an impact on Hawaii. Thanks so much for being part of our ThinkTech family and for supporting our open discussion of tech, energy, diversification and global awareness in Hawaii. And of course the ongoing search for innovation wherever we can find it. You can watch this show throughout the week and tune in next Sunday evening for our next important weekly episode. I'm Cynthia Sinclair. And I'm Anna Jimenez-McMillan. Aloha everyone.