1 00:00:01,110 --> 00:00:04,159 How does a sea snail catch a fish? 2 00:00:04,183 --> 00:00:06,706 I mean, it's a snail, so it's slow, 3 00:00:06,730 --> 00:00:09,645 and the fish is not. 4 00:00:10,110 --> 00:00:12,149 But yet, this happens. 5 00:00:12,817 --> 00:00:15,419 Hidden under the sand is a cone snail. 6 00:00:15,443 --> 00:00:18,230 And that orange thing you see is kind of like a tongue. 7 00:00:18,254 --> 00:00:20,071 We call it a proboscis. 8 00:00:20,095 --> 00:00:24,975 It uses that to track and subdue this unsuspecting fish. 9 00:00:26,046 --> 00:00:28,022 In this predator-prey interaction, 10 00:00:28,046 --> 00:00:31,395 these are clearly not your garden variety escargots. 11 00:00:31,419 --> 00:00:34,482 These are assassins of the sea. 12 00:00:35,102 --> 00:00:38,045 And their weapon of choice is venom. 13 00:00:38,069 --> 00:00:42,332 Venom, like the venom you find in venomous snakes and scorpions, 14 00:00:42,356 --> 00:00:46,935 these sea snails, they use their venom to subdue fish, worms 15 00:00:46,959 --> 00:00:48,240 and other snails. 16 00:00:48,264 --> 00:00:49,716 And the venom of these snails, 17 00:00:49,740 --> 00:00:50,904 it's not just one thing, 18 00:00:50,928 --> 00:00:54,577 it's actually a cocktail of toxic molecules 19 00:00:54,601 --> 00:00:59,132 that are packaged and delivered through a false tooth called a radula. 20 00:00:59,156 --> 00:01:02,133 You can think of the radulas as hypodermic needles. 21 00:01:02,157 --> 00:01:03,323 Now, no need to worry, 22 00:01:03,347 --> 00:01:05,599 these snails are practicing good needle habits, 23 00:01:05,623 --> 00:01:08,122 because each radula is only used once. 24 00:01:08,146 --> 00:01:11,249 Now from your own knowledge about venomous organisms, 25 00:01:11,273 --> 00:01:15,151 and the keep-you-up-at-night fish-killing video that I just showed you, 26 00:01:15,175 --> 00:01:18,944 you might think that venom is dangerous and all bad. 27 00:01:18,968 --> 00:01:20,865 Well, yes and no. 28 00:01:20,889 --> 00:01:22,815 A more accurate way of thinking of venom 29 00:01:22,839 --> 00:01:27,426 is to think of it as both a supervillain and a superhero. 30 00:01:27,450 --> 00:01:30,966 In my lab, we study the evolution of venom in these sea snails 31 00:01:30,990 --> 00:01:32,514 as a force for good. 32 00:01:32,538 --> 00:01:34,093 Sounds like a stretch, 33 00:01:34,117 --> 00:01:35,712 or maybe even snake oil, 34 00:01:35,736 --> 00:01:36,909 but actually, 35 00:01:36,933 --> 00:01:39,688 while there are snakes involved, the product is legit. 36 00:01:39,712 --> 00:01:42,156 One reason the venom product is so successful 37 00:01:42,180 --> 00:01:47,337 is that it transforms a physical warfare into a biochemical one. 38 00:01:47,361 --> 00:01:51,535 Where usually the predator-prey interaction is one of brute force, 39 00:01:51,559 --> 00:01:53,736 venom takes it to a molecular scale. 40 00:01:53,760 --> 00:01:55,879 And it's not size that matters, 41 00:01:55,903 --> 00:01:58,006 but the mixture of your venom arsenal. 42 00:01:58,030 --> 00:02:00,561 The chemistry of the toxins in your arsenal 43 00:02:00,585 --> 00:02:04,030 is what's going to enable David to conquer Goliath. 44 00:02:04,054 --> 00:02:07,411 And in our scenario, David is clearly the snail. 45 00:02:07,435 --> 00:02:10,578 Another feature of venom that makes it so successful 46 00:02:10,602 --> 00:02:14,836 is that the toxins work with the precision of a Swiss Army knife. 47 00:02:14,860 --> 00:02:16,059 And so these toxins, 48 00:02:16,083 --> 00:02:19,875 they come for strongholds that help an organism to function. 49 00:02:19,899 --> 00:02:23,434 So they target blood, brain and membranes. 50 00:02:23,458 --> 00:02:26,037 Whether it's snail venom or snake venom, 51 00:02:26,061 --> 00:02:28,537 they each have components that can do things 52 00:02:28,561 --> 00:02:30,593 like cause your blood to clot, 53 00:02:30,617 --> 00:02:32,403 what we call "hemotoxic." 54 00:02:32,427 --> 00:02:36,467 Or they cause neurons in your brains to not function normally, 55 00:02:36,491 --> 00:02:37,951 what we call "neurotoxic." 56 00:02:37,975 --> 00:02:42,411 Or they have toxins that will poke holes into the membranes of your cells, 57 00:02:42,435 --> 00:02:45,708 causing them to rupture and, basically, explode, 58 00:02:45,732 --> 00:02:47,439 what we call "cytotoxic." 59 00:02:47,463 --> 00:02:49,693 Cellular explosion, people. 60 00:02:49,717 --> 00:02:52,653 Now, if that is not all powerful and all present, 61 00:02:52,677 --> 00:02:53,944 nothing is. 62 00:02:53,968 --> 00:02:55,564 Now a little about me, 63 00:02:55,588 --> 00:02:57,999 and why I'm so obsessed with venom. 64 00:02:58,579 --> 00:03:00,347 I grew up in New York City 65 00:03:00,371 --> 00:03:03,387 with forced access to the Natural History Museum. 66 00:03:03,411 --> 00:03:04,799 I say "forced access," 67 00:03:04,823 --> 00:03:06,289 because I'm one of five kids, 68 00:03:06,313 --> 00:03:09,894 and my parents used museums as a form of childcare. 69 00:03:10,253 --> 00:03:11,452 There were two rules: 70 00:03:11,476 --> 00:03:12,737 Don't lose anybody 71 00:03:12,761 --> 00:03:15,087 and meet Mom and Dad at the African elephants 72 00:03:15,111 --> 00:03:17,483 at 5:30, when the museum closes. 73 00:03:17,507 --> 00:03:23,138 Those totally unsupervised days running through the halls of the museum 74 00:03:23,162 --> 00:03:25,974 were full of adventure and exploration. 75 00:03:25,998 --> 00:03:28,569 And that's how I feel when I'm studying venom. 76 00:03:28,593 --> 00:03:30,307 It's a scientific adventure. 77 00:03:30,331 --> 00:03:35,587 We're boldly exploring this entity that connects nature and humanity. 78 00:03:35,611 --> 00:03:37,817 Another reason that I'm obsessed with venom 79 00:03:37,841 --> 00:03:39,585 is because of its duality. 80 00:03:39,609 --> 00:03:43,252 When you inject the components of a venom arsenal into an organism, 81 00:03:43,276 --> 00:03:45,633 it can kill or it can cure. 82 00:03:45,657 --> 00:03:48,299 At a molecular level, several things can happen. 83 00:03:48,601 --> 00:03:51,704 You saw one thing, paralysis in the fish. 84 00:03:52,134 --> 00:03:54,666 Now that was happening because the toxins in the venom 85 00:03:54,690 --> 00:03:57,927 were attacking how the fish's cells communicate with each other, 86 00:03:57,951 --> 00:03:59,982 preventing it from swimming away. 87 00:04:00,006 --> 00:04:03,334 Are there other things that I would like to use venom to attack? 88 00:04:03,760 --> 00:04:04,926 For sure. 89 00:04:04,950 --> 00:04:06,768 And one of those is cancer. 90 00:04:06,792 --> 00:04:08,848 Cancer tumors are cells. 91 00:04:08,872 --> 00:04:10,031 And like all cells, 92 00:04:10,055 --> 00:04:13,228 they communicate with themselves and their environment around them. 93 00:04:13,252 --> 00:04:15,434 So we would like to find venom components 94 00:04:15,458 --> 00:04:19,354 that are very good at disrupting how the tumor cells communicate. 95 00:04:19,378 --> 00:04:24,188 Similar to how the venom disrupted how the fish cells communicated 96 00:04:24,212 --> 00:04:26,291 and the fish couldn't swim away. 97 00:04:26,315 --> 00:04:29,654 In my lab, we study cancer as a channelopathy. 98 00:04:29,998 --> 00:04:33,405 What this means is, basically, we're looking for venom components 99 00:04:33,429 --> 00:04:37,231 that will target channels that are overexpressed in tumor cells 100 00:04:37,255 --> 00:04:38,540 versus normal cells. 101 00:04:38,564 --> 00:04:41,085 The cancer that we're most focused on right now 102 00:04:41,109 --> 00:04:42,442 is liver cancer. 103 00:04:42,466 --> 00:04:44,808 And that's because since the 1980s, 104 00:04:44,832 --> 00:04:47,537 the death rate of liver cancer has doubled, 105 00:04:47,561 --> 00:04:49,942 and it's an emerging threat in the US. 106 00:04:49,966 --> 00:04:52,260 In a screen in which we had cervical, 107 00:04:52,284 --> 00:04:55,483 neuroblastoma, prostate and liver cancer cells, 108 00:04:55,507 --> 00:04:57,998 we found a compound from a terebrid snail 109 00:04:58,022 --> 00:05:01,315 that seems to attack liver cancer cells, 110 00:05:01,339 --> 00:05:05,022 and only liver cancer cells, and none of the others that were tested. 111 00:05:05,046 --> 00:05:08,490 And then, when we took this compound and we injected it into mouse models 112 00:05:08,514 --> 00:05:10,507 that were expressing liver cancer cells, 113 00:05:10,531 --> 00:05:13,766 it significantly inhibited the growth of the tumors. 114 00:05:13,790 --> 00:05:16,006 We're not quite sure how this works yet, 115 00:05:16,030 --> 00:05:17,895 we're still investigating the mechanism 116 00:05:17,919 --> 00:05:20,673 and how we can make this compound more effective, 117 00:05:20,697 --> 00:05:22,640 so you can't rush out to the pharmacy 118 00:05:22,664 --> 00:05:26,847 and order up a killer snail liver-cancer therapy treatment. 119 00:05:26,871 --> 00:05:28,109 Not yet. 120 00:05:28,450 --> 00:05:30,283 Basically, what we think is happening 121 00:05:30,307 --> 00:05:33,823 is that the compound is blocking a specific channel, 122 00:05:33,847 --> 00:05:36,609 prohibiting the transmission of a specific chemical 123 00:05:36,633 --> 00:05:38,846 that leads to downstream signaling 124 00:05:38,870 --> 00:05:43,132 that enables the tumor to multiply and draw blood to itself. 125 00:05:43,156 --> 00:05:46,133 What we're doing in studying the components of venom 126 00:05:46,157 --> 00:05:48,848 to find treatments for human diseases and disorders, 127 00:05:48,872 --> 00:05:50,156 is not new, 128 00:05:50,180 --> 00:05:52,950 it's what we call natural products drug discovery, 129 00:05:52,974 --> 00:05:54,784 and it's been happening for centuries, 130 00:05:54,808 --> 00:05:56,990 and in cultures all over the world. 131 00:05:57,014 --> 00:05:59,474 Venoms are not only giving us cool new compounds, 132 00:05:59,498 --> 00:06:02,284 but they're also giving us new ways of thinking 133 00:06:02,308 --> 00:06:05,185 about how we treat human diseases and disorders. 134 00:06:05,521 --> 00:06:07,267 And I'll give you three examples. 135 00:06:07,291 --> 00:06:10,117 The first is from killer snails, of course. 136 00:06:10,141 --> 00:06:14,037 And so the first drug from these snails that is on the market 137 00:06:14,061 --> 00:06:16,863 is called ziconotide, or Prialt, 138 00:06:16,887 --> 00:06:20,989 and it's used to treat chronic pain in HIV and cancer patients. 139 00:06:21,013 --> 00:06:23,790 Prialt is a nonaddictive pain therapy. 140 00:06:24,227 --> 00:06:28,185 Three magic words when you think about how we're treating pain currently. 141 00:06:28,209 --> 00:06:31,550 We're using things that have a huge cost of addiction. 142 00:06:31,574 --> 00:06:32,743 So think of morphine 143 00:06:32,767 --> 00:06:35,609 or think of any of your favorite opioid out there. 144 00:06:35,633 --> 00:06:36,895 What the snails have done 145 00:06:36,919 --> 00:06:41,332 is they've shown us a way to treat pain without the addiction, 146 00:06:41,356 --> 00:06:42,506 which is huge. 147 00:06:43,055 --> 00:06:46,364 The next example comes from the Brazilian pit viper. 148 00:06:46,388 --> 00:06:49,776 From these snakes, we've derived a compound called captopril. 149 00:06:49,800 --> 00:06:52,879 Captopril is used to treat high blood pressure, 150 00:06:52,903 --> 00:06:55,403 and captopril is a breakthrough drug. 151 00:06:55,427 --> 00:06:57,577 But not only in and of itself, 152 00:06:57,601 --> 00:07:00,529 but because it advanced a whole class of drugs, 153 00:07:00,553 --> 00:07:02,609 what we know as ACE inhibitors, 154 00:07:02,633 --> 00:07:06,133 which are the most commonly [prescribed] for treating hypertension 155 00:07:06,157 --> 00:07:07,585 and heart failure. 156 00:07:07,609 --> 00:07:11,387 The last example is from the Gila monster. 157 00:07:11,411 --> 00:07:15,332 And this is a really exciting example of understanding the ecology 158 00:07:15,356 --> 00:07:16,705 of these organisms, 159 00:07:16,729 --> 00:07:19,037 and pairing it with efficient drug discovery. 160 00:07:19,061 --> 00:07:21,125 And Gila monsters are binge eaters. 161 00:07:21,149 --> 00:07:23,537 So when they bite into a large meal, 162 00:07:23,561 --> 00:07:26,955 they release things in their venom that lower blood sugar. 163 00:07:26,979 --> 00:07:30,892 So what's the drug that you think we found from the Gila monster? 164 00:07:30,916 --> 00:07:35,116 A compound that is used to lower the blood sugar in diabetic patients. 165 00:07:35,140 --> 00:07:37,188 Now these are three marvelous examples, 166 00:07:37,212 --> 00:07:39,260 but we've just scratched the surface. 167 00:07:39,284 --> 00:07:42,077 There's so much more venom out there for us to study. 168 00:07:42,101 --> 00:07:45,673 In fact, we think that 15 percent of all the animals on the planet 169 00:07:45,697 --> 00:07:46,880 are venomous. 170 00:07:46,904 --> 00:07:48,594 And I think this is a low estimate, 171 00:07:48,618 --> 00:07:51,959 given the fact that we haven't surveyed all the animals on the planet. 172 00:07:51,983 --> 00:07:54,630 But nature seems to have found something that she likes, 173 00:07:54,654 --> 00:07:57,853 and she's repeated it over and over and over again, 174 00:07:57,877 --> 00:08:00,615 leading to the vast array of animals that we see around us 175 00:08:00,639 --> 00:08:02,576 and all throughout the tree of life. 176 00:08:02,600 --> 00:08:06,156 So whether we're talking about my fave, killer snails, 177 00:08:06,180 --> 00:08:07,449 or jellyfish, 178 00:08:07,473 --> 00:08:10,228 or the larvae of butterflies and moths, 179 00:08:10,252 --> 00:08:12,863 or platypus or slow lorises, 180 00:08:12,887 --> 00:08:15,887 whether by sea, land or air, 181 00:08:15,911 --> 00:08:18,633 you're sure to encounter a venomous creature. 182 00:08:18,657 --> 00:08:20,069 Remember when I told you 183 00:08:20,093 --> 00:08:24,188 that venom can be both a superhero and a supervillain, 184 00:08:24,212 --> 00:08:25,768 and you doubted me? 185 00:08:25,792 --> 00:08:26,974 Mhm. 186 00:08:26,998 --> 00:08:30,086 We're in a race to harness all of this venom goodness 187 00:08:30,110 --> 00:08:33,110 before we lose the vast majority of animals on our planet. 188 00:08:33,134 --> 00:08:34,840 It's a holistic process. 189 00:08:34,864 --> 00:08:39,426 You can't have the therapeutic treatments without having the animals. 190 00:08:39,450 --> 00:08:41,085 And you can't have the animals 191 00:08:41,109 --> 00:08:42,856 without having their ecosystems. 192 00:08:42,880 --> 00:08:44,539 So for me and the snails, 193 00:08:44,563 --> 00:08:47,318 what it means is we have to save the oceans. 194 00:08:47,342 --> 00:08:49,739 And because venomous animals are found everywhere, 195 00:08:49,763 --> 00:08:51,778 we basically have to save the planet. 196 00:08:51,802 --> 00:08:53,548 So do it for the venomous animals, 197 00:08:53,572 --> 00:08:55,491 if you don't want to do it for yourself. 198 00:08:55,515 --> 00:08:56,682 And who knows, 199 00:08:56,706 --> 00:08:59,992 some day, snail venom might just save your life. 200 00:09:00,952 --> 00:09:02,102 Thank you.