1 00:00:02,369 --> 00:00:06,273 >>NARRATOR: A vast expanse of liquid hope, 2 00:00:06,273 --> 00:00:10,377 the oceans are part of America's newest medical frontier. 3 00:00:13,614 --> 00:00:18,719 Its underwater organisms are teeming with potential cures. 4 00:00:20,254 --> 00:00:24,324 >>Sponges are providing real chemicals, real pharmaceuticals. 5 00:00:24,324 --> 00:00:29,296 >>About 70% of the drugs that we use now have their origin 6 00:00:29,296 --> 00:00:30,831 in some natural product. 7 00:00:30,831 --> 00:00:32,499 Most of them are plant-derived. 8 00:00:32,499 --> 00:00:35,836 So can you imagine how much more there is 9 00:00:35,836 --> 00:00:39,339 when two-thirds of the world is covered by water? 10 00:00:39,339 --> 00:00:42,543 The potential is unlimited. 11 00:00:43,877 --> 00:00:46,914 >>NARRATOR: The latest medical gold rush 12 00:00:46,914 --> 00:00:50,317 takes place beneath the waves. 13 00:00:50,317 --> 00:00:53,387 Marine creatures may hold the key 14 00:00:53,387 --> 00:00:58,425 to unlocking the secrets of our own biology. 15 00:01:00,193 --> 00:01:02,563 >>The horseshoe crab and its eyes 16 00:01:02,563 --> 00:01:04,097 are really quite remarkable. 17 00:01:04,097 --> 00:01:06,266 They become about a million times more sensitive at night 18 00:01:06,266 --> 00:01:08,235 than they are during the day. 19 00:01:08,235 --> 00:01:10,971 >>We've used that information to be able to get a better sense 20 00:01:10,971 --> 00:01:12,839 of how human eyes work. 21 00:01:19,680 --> 00:01:23,116 >>Aplysia fits the niche for a basic animal 22 00:01:23,116 --> 00:01:27,621 that can be used to study memory and learning. 23 00:01:27,621 --> 00:01:30,857 >>The compound that comes from a shallow water sponge 24 00:01:30,857 --> 00:01:34,061 can help to block the spread of cancer. 25 00:01:35,662 --> 00:01:39,266 >>NARRATOR: Scientists view this saltwater wilderness 26 00:01:39,266 --> 00:01:43,070 as a treasure chest of promise for human medicine. 27 00:01:43,070 --> 00:01:46,340 >>I still feel like I'm a kid in a candy store, 28 00:01:46,340 --> 00:01:50,010 because marine natural products are amazing. 29 00:01:50,010 --> 00:01:52,813 They have such potential to really be new drugs, 30 00:01:52,813 --> 00:01:56,617 and yet we have just scratched the surface. 31 00:01:58,952 --> 00:02:00,954 >>NARRATOR: The ocean's medical mysteries 32 00:02:00,954 --> 00:02:03,890 are as deep as its trenches. 33 00:02:03,890 --> 00:02:09,029 What breakthroughs have its sea life revealed? 34 00:02:09,029 --> 00:02:12,566 Are there cures that lie beneath the waves? 35 00:02:37,758 --> 00:02:40,961 >>Major funding for this program was provided 36 00:02:40,961 --> 00:02:42,796 by the Batchelor Foundation, 37 00:02:42,796 --> 00:02:45,465 encouraging people to preserve and protect 38 00:02:45,465 --> 00:02:48,468 America's underwater resources. 39 00:03:02,382 --> 00:03:04,651 >>NARRATOR: For centuries, man has looked to the oceans 40 00:03:04,651 --> 00:03:09,256 for organic remedies to alleviate human illness. 41 00:03:09,256 --> 00:03:15,128 In 1987, a chemical isolated from a Caribbean sponge 42 00:03:15,128 --> 00:03:20,033 was the first drug approved for treatment of the HIV infection. 43 00:03:20,033 --> 00:03:23,236 Toxins from a venomous cone snail 44 00:03:23,236 --> 00:03:27,674 offer relief to those suffering from severe chronic pain. 45 00:03:29,342 --> 00:03:33,013 Once again, the seas are proving to be 46 00:03:33,013 --> 00:03:37,684 a valuable resource for medical research. 47 00:03:37,684 --> 00:03:39,686 >>Over the last ten to 20 years, 48 00:03:39,686 --> 00:03:41,788 we've been doing more and more research in this environment, 49 00:03:41,788 --> 00:03:42,989 looking at the marine environment, 50 00:03:42,989 --> 00:03:45,959 looking at shallow waters, going into deep waters. 51 00:03:45,959 --> 00:03:47,994 And with our work, 52 00:03:47,994 --> 00:03:49,996 we're looking at things which are associated 53 00:03:49,996 --> 00:03:51,798 with invertebrates. 54 00:04:02,075 --> 00:04:04,678 >>NARRATOR: In Florida, a team of scientists 55 00:04:04,678 --> 00:04:06,913 at Harbor Branch Oceanographic Institute 56 00:04:06,913 --> 00:04:08,982 are testing sea sponges 57 00:04:08,982 --> 00:04:12,352 for their potential anticancer properties. 58 00:04:14,254 --> 00:04:17,591 >>Our main focus right now is pancreatic cancer, 59 00:04:17,591 --> 00:04:19,860 because it is the fourth leading cause of death 60 00:04:19,860 --> 00:04:21,194 of cancer in the U.S., 61 00:04:21,194 --> 00:04:26,299 and it is one of those that only has a 5% survival rate. 62 00:04:26,299 --> 00:04:29,836 So that means only 5% of the patients make it past five years 63 00:04:29,836 --> 00:04:31,505 of being diagnosed. 64 00:04:31,505 --> 00:04:34,274 So the drugs that we have right now are not very effective, 65 00:04:34,274 --> 00:04:37,410 and we desperately need new drugs for pancreatic cancer. 66 00:04:41,348 --> 00:04:45,652 Normally, the way it goes, we go on the sub, you get a sponge, 67 00:04:45,652 --> 00:04:49,289 the chemists make extracts and then we test different abilities 68 00:04:49,289 --> 00:04:52,092 that these compounds might have to fight cancer. 69 00:04:52,092 --> 00:04:53,994 >>NARRATOR: The Center for Marine Biomedical 70 00:04:53,994 --> 00:04:56,863 and Biotechnology Research at Harbor Branch 71 00:04:56,863 --> 00:04:59,900 houses invertebrate specimens that have been collected 72 00:04:59,900 --> 00:05:02,202 throughout the world's oceans. 73 00:05:05,372 --> 00:05:08,608 Explorers use state-of-the-art research vessels 74 00:05:08,608 --> 00:05:13,113 and manned submersibles to gather sea-dwelling creatures. 75 00:05:13,113 --> 00:05:15,682 >>So Harbor Branch has had the Johnson Sea Link submersibles, 76 00:05:15,682 --> 00:05:20,187 and they dive to 3,000 feet of seawater-- or 910 meters-- 77 00:05:20,187 --> 00:05:23,123 and they are fully outfitted with a work platform 78 00:05:23,123 --> 00:05:26,459 that allows us to collect different organisms. 79 00:05:31,331 --> 00:05:34,134 >>NARRATOR: Once an organism has been collected, 80 00:05:34,134 --> 00:05:36,703 chemists break down the specimen 81 00:05:36,703 --> 00:05:39,773 and begin the process of purification. 82 00:05:39,773 --> 00:05:42,843 After an extract has been isolated, 83 00:05:42,843 --> 00:05:44,711 scientists like Dr. Esther Guzman 84 00:05:44,711 --> 00:05:48,248 perform a series of tests to determine 85 00:05:48,248 --> 00:05:53,153 if the item shows activity against cancer cells. 86 00:05:53,153 --> 00:05:56,623 >>Sponges cannot do much other than being in their little site, 87 00:05:56,623 --> 00:05:59,226 so that makes them nice little chemical factories, 88 00:05:59,226 --> 00:06:02,229 because everything that they want to do, 89 00:06:02,229 --> 00:06:05,198 whether it's grow or expand 90 00:06:05,198 --> 00:06:08,201 or attract another sponge to reproduce, 91 00:06:08,201 --> 00:06:11,538 they do this by releasing things into the water. 92 00:06:11,538 --> 00:06:14,507 That little sponge, as innocent as it looks, 93 00:06:14,507 --> 00:06:17,677 it's making some very heavy chemicals. 94 00:06:17,677 --> 00:06:20,881 If you put, for example, a drop of perfume in a glass of water, 95 00:06:20,881 --> 00:06:22,415 you're going to lose that smell. 96 00:06:22,415 --> 00:06:26,620 So think about how potent the signals of a sponge are, 97 00:06:26,620 --> 00:06:29,456 because they are releasing it in more than a glass of water; 98 00:06:29,456 --> 00:06:31,291 they are releasing it to the sea. 99 00:06:40,500 --> 00:06:42,168 >>NARRATOR: One of these "chemical factories" 100 00:06:42,168 --> 00:06:44,504 is the Caribbean barrel sponge. 101 00:06:46,473 --> 00:06:49,276 It contains a compound called manzamine A, 102 00:06:49,276 --> 00:06:52,379 which has drawn a lot of attention from scientists. 103 00:06:53,947 --> 00:06:56,483 >>We've shown recently it can help to block 104 00:06:56,483 --> 00:06:57,851 the spread of the cancer. 105 00:06:57,851 --> 00:07:00,887 >>If you think about pancreatic cancer, 106 00:07:00,887 --> 00:07:02,656 the reason it's very aggressive 107 00:07:02,656 --> 00:07:04,190 is that normally when it's detected, 108 00:07:04,190 --> 00:07:07,093 it has already migrated to another organ, 109 00:07:07,093 --> 00:07:09,296 so it has already metastasized. 110 00:07:09,296 --> 00:07:11,364 Manzamine A stops that process. 111 00:07:11,364 --> 00:07:13,767 One of the characteristics of cancer cells 112 00:07:13,767 --> 00:07:16,503 is that they don't need this cell-to-cell interaction. 113 00:07:16,503 --> 00:07:19,039 They actually thrive on their own, 114 00:07:19,039 --> 00:07:21,474 and that might be one of the characteristics also 115 00:07:21,474 --> 00:07:24,811 that can lead to this spreading to another organ. 116 00:07:24,811 --> 00:07:27,747 And if you put manzamine A in their midst at low doses, 117 00:07:27,747 --> 00:07:30,684 it kind of returns the cell-to-cell interaction. 118 00:07:30,684 --> 00:07:33,186 It also prevents the cells from migrating 119 00:07:33,186 --> 00:07:36,089 from one organ to another. 120 00:07:38,058 --> 00:07:40,260 >>NARRATOR: In addition to manzamine A, 121 00:07:40,260 --> 00:07:42,696 another sponge extract that shows promise 122 00:07:42,696 --> 00:07:46,666 for cancer therapies is discodermolide. 123 00:07:46,666 --> 00:07:49,536 Initially developed as an immunosuppressant, 124 00:07:49,536 --> 00:07:54,441 discodermolide, which comes from a Bahamian sea sponge, 125 00:07:54,441 --> 00:07:57,344 functions similarly to Taxol, 126 00:07:57,344 --> 00:08:00,513 a pharmaceutical commonly used to treat patients with ovarian, 127 00:08:00,513 --> 00:08:03,350 breast or lung cancer, 128 00:08:03,350 --> 00:08:07,020 as well as patients with AIDS-related Kaposi's sarcoma. 129 00:08:08,388 --> 00:08:11,958 >>Taxol is one of the major drugs used to treat cancer, 130 00:08:11,958 --> 00:08:15,628 and it was isolated from a yew tree. 131 00:08:15,628 --> 00:08:19,366 The way Taxol works is that it freezes 132 00:08:19,366 --> 00:08:21,968 or hyper-stabilizes tubulin. 133 00:08:21,968 --> 00:08:24,904 Tubulin is a protein that is in all your cells. 134 00:08:24,904 --> 00:08:26,606 and it helps to give cells shape. 135 00:08:26,606 --> 00:08:30,110 It is very necessary when the cells are going to divide. 136 00:08:30,110 --> 00:08:32,445 When you put Taxol in a cell that is dividing, 137 00:08:32,445 --> 00:08:34,814 the cell can no longer align itself, 138 00:08:34,814 --> 00:08:36,883 and so these cells will die. 139 00:08:36,883 --> 00:08:38,785 There are certain tumors that do not respond to it, 140 00:08:38,785 --> 00:08:41,388 and there are certain tumors that become resistant to it. 141 00:08:41,388 --> 00:08:45,725 Discodermolide is about the same potency as Taxol, 142 00:08:45,725 --> 00:08:48,128 but it is still effective on cells 143 00:08:48,128 --> 00:08:49,896 that have become resistant to Taxol. 144 00:09:02,342 --> 00:09:05,645 >>NARRATOR: Researchers at Harbor Branch 145 00:09:05,645 --> 00:09:08,148 are also looking for chemical agents that can target 146 00:09:08,148 --> 00:09:10,650 malignant cells efficiently 147 00:09:10,650 --> 00:09:15,021 without suppressing healthy body systems. 148 00:09:15,021 --> 00:09:17,123 >>One of the major problems that we have 149 00:09:17,123 --> 00:09:19,659 with cancer treatments or with chemotherapies 150 00:09:19,659 --> 00:09:22,095 is that you tend to kill normal cells 151 00:09:22,095 --> 00:09:25,131 as much as you're killing cancer cells. 152 00:09:26,466 --> 00:09:29,469 >>NARRATOR: A sponge found in Bahamian waters 153 00:09:29,469 --> 00:09:32,439 contains a compound that may help reduce 154 00:09:32,439 --> 00:09:37,577 patient side effects through cell selectivity. 155 00:09:37,577 --> 00:09:40,480 Leiodermatolide, its chemical extract, 156 00:09:40,480 --> 00:09:43,583 shows greater activity against cancer cells 157 00:09:43,583 --> 00:09:45,452 than healthy cells. 158 00:09:45,452 --> 00:09:47,754 >>Having this selectivity-- that it kills 159 00:09:47,754 --> 00:09:51,591 6,000 times more cancer cells than normal cells-- 160 00:09:51,591 --> 00:09:53,993 is that then you will have less side effects, 161 00:09:53,993 --> 00:09:57,530 because in certain senses you are weakening the patient 162 00:09:57,530 --> 00:09:59,999 while you are trying to kill the cancer. 163 00:10:02,068 --> 00:10:04,337 >>NARRATOR: The marine natural products from Harbor Branch 164 00:10:04,337 --> 00:10:06,773 are in various stages of testing. 165 00:10:06,773 --> 00:10:08,341 Getting drugs approved 166 00:10:08,341 --> 00:10:10,443 by the U.S. Food and Drug Administration 167 00:10:10,443 --> 00:10:12,445 is a lengthy process, 168 00:10:12,445 --> 00:10:15,715 one that can take years before the public can gain access 169 00:10:15,715 --> 00:10:18,852 to novel compounds such as these. 170 00:10:19,953 --> 00:10:23,256 However, cancer biologists like Dr. Guzman 171 00:10:23,256 --> 00:10:26,926 are still optimistic that sponges will one day 172 00:10:26,926 --> 00:10:31,631 provide better medicines to treat pancreatic cancer. 173 00:10:43,943 --> 00:10:47,714 They are living fossils. 174 00:10:47,714 --> 00:10:50,583 Horseshoe crabs are curiously resilient 175 00:10:50,583 --> 00:10:53,553 and unassuming creatures whose unique biology 176 00:10:53,553 --> 00:10:57,824 has captivated the interest of man for decades. 177 00:10:57,824 --> 00:11:00,760 More closely related to spiders and scorpions 178 00:11:00,760 --> 00:11:04,230 than to true crabs, ancestors of horseshoe crabs 179 00:11:04,230 --> 00:11:07,967 existed 350 million years ago, 180 00:11:07,967 --> 00:11:11,504 long before the age of dinosaurs. 181 00:11:13,006 --> 00:11:14,674 In the 1900s, 182 00:11:14,674 --> 00:11:17,443 horseshoe crabs were commonly used in the farming industry 183 00:11:17,443 --> 00:11:22,849 as crop fertilizers and as feed for livestock. 184 00:11:22,849 --> 00:11:24,584 By the mid-1970s, 185 00:11:24,584 --> 00:11:27,120 commercial fishermen began using them as bait 186 00:11:27,120 --> 00:11:29,689 for eel and conch fisheries. 187 00:11:29,689 --> 00:11:32,091 But it's the crab's "blue blood" 188 00:11:32,091 --> 00:11:36,396 that revolutionized the medical industry. 189 00:11:36,396 --> 00:11:40,533 >>They have a special chemical in their blood 190 00:11:40,533 --> 00:11:42,936 that's used to detect the presence of bacterium. 191 00:11:42,936 --> 00:11:46,639 >>That bacterium assay is used to screen everything 192 00:11:46,639 --> 00:11:50,944 that goes into a human being and to test 193 00:11:50,944 --> 00:11:53,046 the sterility of all the machines that are used 194 00:11:53,046 --> 00:11:56,883 to deliver such products, like IV fluids. 195 00:11:56,883 --> 00:11:59,319 >>NARRATOR: And that's not the only factor 196 00:11:59,319 --> 00:12:03,189 that makes horseshoe crabs of interest to modern science. 197 00:12:03,189 --> 00:12:06,426 Dr. Barbara Battelle from the University of Florida's 198 00:12:06,426 --> 00:12:10,630 Whitney Lab for Marine Bioscience in Marineland 199 00:12:10,630 --> 00:12:14,601 focuses on the animal's distinct visual system. 200 00:12:14,601 --> 00:12:17,003 >>Well, it has ten eyes-- 201 00:12:17,003 --> 00:12:20,173 two compound eyes that are just like fly eyes. 202 00:12:20,173 --> 00:12:23,810 These are the big eyes that you see on the sides of the carapace 203 00:12:23,810 --> 00:12:25,945 or the upper part of the animal. 204 00:12:25,945 --> 00:12:27,814 And the photoreceptors are very large, 205 00:12:27,814 --> 00:12:31,551 among the largest in nature, so in experimental preparation, 206 00:12:31,551 --> 00:12:33,553 they're really very useful. 207 00:12:34,887 --> 00:12:37,223 >>NARRATOR: Horseshoe crabs have roughly 208 00:12:37,223 --> 00:12:39,892 1,000 photoreceptors, or light-sensitive cells, 209 00:12:39,892 --> 00:12:41,327 in each compound eye, 210 00:12:41,327 --> 00:12:45,164 compared to the millions found in human eyes. 211 00:12:45,164 --> 00:12:47,800 >>There are many people that have reduced vision, 212 00:12:47,800 --> 00:12:50,136 and we don't have an explanation for it. 213 00:12:50,136 --> 00:12:51,571 Why is vision going down? 214 00:12:51,571 --> 00:12:54,040 How does that happen? 215 00:12:54,040 --> 00:12:55,842 Well, in mammals it's difficult to study, 216 00:12:55,842 --> 00:12:58,211 because our eyes are complex. 217 00:12:59,746 --> 00:13:02,148 >>NARRATOR: In 1976, 218 00:13:02,148 --> 00:13:06,519 researchers from Syracuse University discovered 219 00:13:06,519 --> 00:13:09,188 that manipulation of an optic nerve that transmits signals 220 00:13:09,188 --> 00:13:11,958 from the brain to the compound eyes of a horseshoe crab 221 00:13:11,958 --> 00:13:16,095 mimics the visual function of circadian clocks. 222 00:13:17,930 --> 00:13:19,932 >>Circadian clocks are internal clocks 223 00:13:19,932 --> 00:13:23,269 that we have in our cells and in our brain 224 00:13:23,269 --> 00:13:26,172 that make us change our physiology, day to night. 225 00:13:26,172 --> 00:13:30,009 And we experience the effects of our circadian clocks 226 00:13:30,009 --> 00:13:32,879 when we travel across time zones. 227 00:13:32,879 --> 00:13:34,180 The circadian clock in your brain 228 00:13:34,180 --> 00:13:37,083 doesn't only control your sleep-wake cycle; 229 00:13:37,083 --> 00:13:40,787 it also controls how our eyes work. 230 00:13:42,989 --> 00:13:46,392 >>NARRATOR: In 1967, Dr. Haldan Keffer Hartline 231 00:13:46,392 --> 00:13:49,595 and his colleagues at the Marine Biological Laboratory 232 00:13:49,595 --> 00:13:51,564 in Woods Hole, Massachusetts, 233 00:13:51,564 --> 00:13:56,402 won the Nobel Prize for their work examining horseshoe crabs. 234 00:13:56,402 --> 00:13:59,739 They identified lateral inhibition, 235 00:13:59,739 --> 00:14:02,475 a visual process in animals and humans alike 236 00:14:02,475 --> 00:14:04,844 that enhances contrast, 237 00:14:04,844 --> 00:14:08,648 helping the eye to see borders and edges. 238 00:14:08,648 --> 00:14:12,051 Scientists at the Whitney Lab 239 00:14:12,051 --> 00:14:14,320 hope this species will provide even more clues 240 00:14:14,320 --> 00:14:17,724 on the basic mechanisms of vision. 241 00:14:19,392 --> 00:14:23,963 >>Oftentimes, our circadian rhythms degrade as we age, 242 00:14:23,963 --> 00:14:25,898 and it could be that some of the reasons 243 00:14:25,898 --> 00:14:28,000 for impaired vision as we get older 244 00:14:28,000 --> 00:14:31,304 is that the signals from the circadian clock are degrading, 245 00:14:31,304 --> 00:14:34,073 and the cells aren't getting the information they should get. 246 00:14:35,508 --> 00:14:37,977 >>NARRATOR: To test this theory, 247 00:14:37,977 --> 00:14:41,848 Dr. Battelle works with live specimens from her wet lab, 248 00:14:41,848 --> 00:14:43,349 where a skylight provides 249 00:14:43,349 --> 00:14:46,919 natural day- and night-time light patterns. 250 00:14:46,919 --> 00:14:49,622 Tissue samples from the compound eye 251 00:14:49,622 --> 00:14:53,459 are analyzed to detect any biochemical changes 252 00:14:53,459 --> 00:14:57,864 that occur in response to internal or external stimuli. 253 00:15:06,005 --> 00:15:09,542 >>We discovered a major protein in the photoreceptors. 254 00:15:09,542 --> 00:15:11,310 So a protein is the part of the cell 255 00:15:11,310 --> 00:15:12,979 that actually does the work of the cell. 256 00:15:12,979 --> 00:15:15,515 So we found a major protein 257 00:15:15,515 --> 00:15:17,617 that is changed in response to the signal 258 00:15:17,617 --> 00:15:20,420 from the central 24-hour clock. 259 00:15:20,420 --> 00:15:24,123 And we don't really know what that protein does yet, 260 00:15:24,123 --> 00:15:26,192 but we think it has a major impact 261 00:15:26,192 --> 00:15:29,262 on the way the photoreceptor cells function. 262 00:15:29,262 --> 00:15:31,230 >>NARRATOR: By controlling circadian input 263 00:15:31,230 --> 00:15:33,332 to the compound eye, 264 00:15:33,332 --> 00:15:35,635 lab tests revealed concentrations 265 00:15:35,635 --> 00:15:39,972 of the newly discovered protein, opsin 5. 266 00:15:39,972 --> 00:15:42,208 Although similar proteins are far more abundant 267 00:15:42,208 --> 00:15:44,210 during the night and day, 268 00:15:44,210 --> 00:15:49,048 opsin 5 molecules may still impact photoresponse. 269 00:15:49,048 --> 00:15:51,784 >>So we can see these proteins actually move around. 270 00:15:51,784 --> 00:15:53,886 They're in different places depending on the time of day, 271 00:15:53,886 --> 00:15:57,690 and that gives us some clue 272 00:15:57,690 --> 00:16:00,026 about how the photoreceptor is changing its sensitivity, 273 00:16:00,026 --> 00:16:03,629 day to night-- clock input, no clock input, and so forth. 274 00:16:03,629 --> 00:16:07,266 So it gives us a clue of what's going on inside the cell. 275 00:16:08,668 --> 00:16:10,670 >>NARRATOR: Studies indicate that light, 276 00:16:10,670 --> 00:16:14,674 as well as the animal's circadian clock, 277 00:16:14,674 --> 00:16:17,210 regulate opsin 5 differently 278 00:16:17,210 --> 00:16:20,713 than other photosensitive proteins. 279 00:16:20,713 --> 00:16:23,816 Experts suspect that changes in levels may underlie 280 00:16:23,816 --> 00:16:27,954 some the dramatic day-night changes in photoreceptors. 281 00:16:27,954 --> 00:16:30,223 >>The horseshoe crab and its eyes 282 00:16:30,223 --> 00:16:33,426 become about a million times more sensitive at night 283 00:16:33,426 --> 00:16:36,195 than they are during the day, and what's really interesting 284 00:16:36,195 --> 00:16:39,131 is that we found the same kind of protein 285 00:16:39,131 --> 00:16:42,168 in the photoreceptors of mammals. 286 00:16:42,168 --> 00:16:43,669 And that's the way 287 00:16:43,669 --> 00:16:47,006 the sort of comparative biology that we do works. 288 00:16:47,006 --> 00:16:51,110 We find something in a simpler organism, and then we ask, 289 00:16:51,110 --> 00:16:53,412 "Well, are we finding the same sorts of things 290 00:16:53,412 --> 00:16:56,148 in other organisms?" 291 00:16:56,148 --> 00:16:59,785 Basic mechanisms that go on in cells, regardless of species, 292 00:16:59,785 --> 00:17:01,087 are similar. 293 00:17:01,087 --> 00:17:04,056 And as we discover what this protein does 294 00:17:04,056 --> 00:17:06,225 in the horseshoe crab eye, then we can begin to ask 295 00:17:06,225 --> 00:17:08,528 more pointed questions about what it might be doing 296 00:17:08,528 --> 00:17:10,196 in our own eyes. 297 00:17:10,196 --> 00:17:11,898 So, if we can figure out how to make 298 00:17:11,898 --> 00:17:14,200 cells more sensitive to light, 299 00:17:14,200 --> 00:17:18,137 then the potential is that we can fix them. 300 00:17:28,114 --> 00:17:30,650 >>NARRATOR: Marine invertebrates 301 00:17:30,650 --> 00:17:33,252 are seemingly basic organisms. 302 00:17:37,924 --> 00:17:40,860 Yet their simplistic anatomies offer great insights 303 00:17:40,860 --> 00:17:44,797 into the way the human nervous system functions. 304 00:17:48,000 --> 00:17:52,004 The larvae of starfish help researchers understand 305 00:17:52,004 --> 00:17:55,308 how the body defends itself against disease. 306 00:17:56,909 --> 00:17:59,946 The mechanisms by which nerve impulses travel 307 00:17:59,946 --> 00:18:03,849 along nerve fibers was discovered via studies on squid. 308 00:18:05,718 --> 00:18:10,056 In 2000, experiments with sea slugs won Eric Kandel 309 00:18:10,056 --> 00:18:12,558 and his colleagues at Columbia University 310 00:18:12,558 --> 00:18:14,160 the Nobel Prize in medicine 311 00:18:14,160 --> 00:18:16,896 for their work on the cellular processes 312 00:18:16,896 --> 00:18:19,198 of learning and memory. 313 00:18:21,567 --> 00:18:24,937 The National Resource for Aplysia in Miami 314 00:18:24,937 --> 00:18:27,206 is the only facility in the world 315 00:18:27,206 --> 00:18:32,244 where sea slugs are raised for research purposes. 316 00:18:32,244 --> 00:18:34,580 >> Aplysia californica has become an important model 317 00:18:34,580 --> 00:18:37,717 for studying the development of the nervous system, 318 00:18:37,717 --> 00:18:39,752 learning, behavior. 319 00:18:39,752 --> 00:18:45,291 >>NARRATOR: In 1975, Thomas Capo joined Eric Kandel 320 00:18:45,291 --> 00:18:47,026 at Columbia University, where he worked to improve 321 00:18:47,026 --> 00:18:50,396 the availability of sea slugs, or aplysia, 322 00:18:50,396 --> 00:18:52,798 for year-round studies. 323 00:18:52,798 --> 00:18:55,134 >>Aplysia are an annual animal. 324 00:18:55,134 --> 00:18:59,939 If you want to work with small animals in the late summer, 325 00:18:59,939 --> 00:19:01,574 you can't find them. 326 00:19:01,574 --> 00:19:04,477 Or, if you wanted to work with small animals in the winter, 327 00:19:04,477 --> 00:19:05,778 they're not available. 328 00:19:05,778 --> 00:19:07,179 So what we do here 329 00:19:07,179 --> 00:19:09,482 at the University of Miami's Aplysia Resources, 330 00:19:09,482 --> 00:19:13,152 we raise animals throughout the year. 331 00:19:13,152 --> 00:19:15,087 >>NARRATOR: Before coming to Miami, 332 00:19:15,087 --> 00:19:16,922 researchers moved to Woods Hole, Massachusetts, 333 00:19:16,922 --> 00:19:20,826 where original aquacultural operations began 334 00:19:20,826 --> 00:19:22,928 on Aplysia californica, a species commonly found 335 00:19:22,928 --> 00:19:26,632 on the West Coast of the United States. 336 00:19:26,632 --> 00:19:31,203 >>By 1978, we had moved to Woods Hole, 337 00:19:31,203 --> 00:19:33,472 and it's there that we made the major breakthroughs 338 00:19:33,472 --> 00:19:36,742 in getting large numbers of animals through the larval phase 339 00:19:36,742 --> 00:19:38,611 and the metamorphic phases. 340 00:19:38,611 --> 00:19:41,681 And once we were able to grow large numbers of animals, 341 00:19:41,681 --> 00:19:44,450 it became obvious that we needed a larger facility, 342 00:19:44,450 --> 00:19:48,120 a better facility, and there was a major problem 343 00:19:48,120 --> 00:19:50,956 working in Woods Hole, and that was food supply. 344 00:19:50,956 --> 00:19:55,027 And in Florida, at the University of Miami's 345 00:19:55,027 --> 00:19:57,163 experimental facility on Virginia Beach 346 00:19:57,163 --> 00:19:59,598 was the ideal place, 347 00:19:59,598 --> 00:20:01,467 because not only did we have an abundant supply 348 00:20:01,467 --> 00:20:02,902 of ambient seawater, 349 00:20:02,902 --> 00:20:05,071 we also had warm weather to culture the algae. 350 00:20:05,071 --> 00:20:11,277 And within two or three years of moving here in 1989, 351 00:20:11,277 --> 00:20:14,280 we were able to culture over 300, 352 00:20:14,280 --> 00:20:16,215 400 pounds of seaweed a week, 353 00:20:16,215 --> 00:20:20,786 which was necessary to produce the animals. 354 00:20:20,786 --> 00:20:23,723 And also, we had an abundant supply of raw seawater 355 00:20:23,723 --> 00:20:27,159 which we could clean up, chill down 356 00:20:27,159 --> 00:20:28,994 and grow our animals in. 357 00:20:28,994 --> 00:20:31,831 The facility was initially set up 358 00:20:31,831 --> 00:20:34,500 to produce around 10,000 animals, 359 00:20:34,500 --> 00:20:36,535 but we've expanded several times over the years, 360 00:20:36,535 --> 00:20:38,337 and now we produce anywhere 361 00:20:38,337 --> 00:20:40,406 between 25,000 and 30,000 animals a year 362 00:20:40,406 --> 00:20:43,175 for researchers around the world. 363 00:20:48,280 --> 00:20:51,951 >>NARRATOR: One of those researchers, Dr. Leonid Moroz, 364 00:20:51,951 --> 00:20:55,654 works at the University of Florida's Whitney Lab. 365 00:20:55,654 --> 00:20:58,524 His studies focus on how individual nerve cells 366 00:20:58,524 --> 00:21:02,394 function in relation to memory and learning. 367 00:21:02,394 --> 00:21:04,864 >>Aplysia offers this opportunity, 368 00:21:04,864 --> 00:21:07,733 because it has a relatively simple neurosystem, 369 00:21:07,733 --> 00:21:11,437 with only about 100 cells per ganglion 370 00:21:11,437 --> 00:21:15,341 and roughly 10,000 cells in the whole brain-- 371 00:21:15,341 --> 00:21:17,409 and, importantly, most of these neurons are giant. 372 00:21:17,409 --> 00:21:19,745 You can study connections of the cells 373 00:21:19,745 --> 00:21:23,015 and, most importantly, you can link everything to behavior. 374 00:21:23,015 --> 00:21:25,117 >>NARRATOR: Aplysia neurons are so large, 375 00:21:25,117 --> 00:21:28,521 they can be seen by the naked eye. 376 00:21:28,521 --> 00:21:32,191 They possess nine groups of nerve cells, or ganglia, 377 00:21:32,191 --> 00:21:35,327 within their bodies, distinct physical features 378 00:21:35,327 --> 00:21:40,065 that help experimental scientists view aplysia 379 00:21:40,065 --> 00:21:44,804 as a model organisms for neuroscience research. 380 00:21:44,804 --> 00:21:47,807 >>Aplysia seem to be an interesting approach, 381 00:21:47,807 --> 00:21:51,710 a reductionist approach whereby you look at an animal 382 00:21:51,710 --> 00:21:53,679 with a small number of neurons 383 00:21:53,679 --> 00:21:56,415 and basically get an understanding 384 00:21:56,415 --> 00:21:59,585 of how the nervous system works. 385 00:21:59,585 --> 00:22:01,754 >>If you remember your first kiss, 386 00:22:01,754 --> 00:22:04,089 more likely what would happen in your brain-- 387 00:22:04,089 --> 00:22:06,892 or happened in your brain-- is that cell A and cell B 388 00:22:06,892 --> 00:22:10,196 and cell C, they just talk to each other, 389 00:22:10,196 --> 00:22:13,766 and synapses, the connections between cells, become stronger 390 00:22:13,766 --> 00:22:15,901 and, more likely, they change shape. 391 00:22:15,901 --> 00:22:18,404 So efficiency of these connections becomes better 392 00:22:18,404 --> 00:22:19,972 or less better. 393 00:22:19,972 --> 00:22:23,108 So if it's better, you will more likely remember something; 394 00:22:23,108 --> 00:22:25,811 if it's weaker, you will lose this memory. 395 00:22:25,811 --> 00:22:29,315 >>NARRATOR: Dr. Moroz examines how aplysia neurons 396 00:22:29,315 --> 00:22:33,652 and synapses change as a result of memory formations. 397 00:22:33,652 --> 00:22:37,823 Similar to Pavlov's famous salivating dogs experiment, 398 00:22:37,823 --> 00:22:42,461 Dr. Moroz can elicit specific behaviors from sea slugs 399 00:22:42,461 --> 00:22:44,597 through basic forms of learning. 400 00:22:44,597 --> 00:22:47,833 >>You give to aplysia a simple task. 401 00:22:47,833 --> 00:22:50,502 You produce tactical stimulation which is associated 402 00:22:50,502 --> 00:22:52,738 with some kind of algae or juice. 403 00:22:52,738 --> 00:22:55,074 In aplysia, you'll produce a feeding reaction 404 00:22:55,074 --> 00:22:57,776 following this weak stimulus, which normally 405 00:22:57,776 --> 00:22:59,478 they do not produce. 406 00:22:59,478 --> 00:23:04,250 So you do, like, 40 repetitions, and aplysia will remember. 407 00:23:04,250 --> 00:23:07,953 So this is a sort of elementary learning and memory. 408 00:23:07,953 --> 00:23:11,290 It's called associative type of memory, when animals associate 409 00:23:11,290 --> 00:23:13,826 to a type of stimulus, make connections, 410 00:23:13,826 --> 00:23:17,830 and basically preserve those connections for quite a while. 411 00:23:17,830 --> 00:23:21,033 So you count the number of synapses between cells 412 00:23:21,033 --> 00:23:24,336 before and after memory formations. 413 00:23:24,336 --> 00:23:26,572 So in older aplysia, this number of connections 414 00:23:26,572 --> 00:23:28,741 becomes weaker, 415 00:23:28,741 --> 00:23:30,743 and a similar process happens in the human brain 416 00:23:30,743 --> 00:23:32,845 or a variety of neurological diseases. 417 00:23:32,845 --> 00:23:35,180 So everything you learn and remember, 418 00:23:35,180 --> 00:23:38,517 it's really linked to how one neuron talks to each other 419 00:23:38,517 --> 00:23:39,952 and how they preserve this efficiency 420 00:23:39,952 --> 00:23:41,120 of these communications. 421 00:23:41,120 --> 00:23:44,657 So you can reduce complex memory process 422 00:23:44,657 --> 00:23:47,660 to the level of only a few cells. 423 00:23:47,660 --> 00:23:49,428 In fact, many people would be surprised 424 00:23:49,428 --> 00:23:51,997 how many neurons would need to form 425 00:23:51,997 --> 00:23:54,867 elementary forms of memory; only three cells is sufficient. 426 00:23:56,035 --> 00:23:59,138 >>NARRATOR: By studying learning and memory 427 00:23:59,138 --> 00:24:01,607 at the cellular level, Dr. Moroz hopes his experiments 428 00:24:01,607 --> 00:24:06,445 will one day lead to solutions for neurodegenerative conditions 429 00:24:06,445 --> 00:24:10,215 such as Alzheimer's and Parkinson's diseases. 430 00:24:10,215 --> 00:24:12,484 >>I bet if you will solve the problem-- 431 00:24:12,484 --> 00:24:15,921 how in aplysia two neurons talk to each other, 432 00:24:15,921 --> 00:24:19,325 how they modify the synapses-- it will be one or another way 433 00:24:19,325 --> 00:24:23,362 to apply it to clinical studies or disease analysis. 434 00:24:30,836 --> 00:24:34,673 >>NARRATOR: Scientists say it is important to study 435 00:24:34,673 --> 00:24:36,542 a diverse group of species 436 00:24:36,542 --> 00:24:39,979 to better understand complicated processes. 437 00:24:39,979 --> 00:24:42,948 >>If everybody looked just at a rat or a mouse, 438 00:24:42,948 --> 00:24:45,050 we'd know a lot about a rat or a mouse, 439 00:24:45,050 --> 00:24:47,319 but we wouldn't have the full spectrum 440 00:24:47,319 --> 00:24:49,488 of understanding about biology. 441 00:24:49,488 --> 00:24:53,826 But by studying these simpler or less complex organisms, 442 00:24:53,826 --> 00:24:55,928 we can learn a lot about basic processes, 443 00:24:55,928 --> 00:24:58,998 and I think that remains critical to our understanding 444 00:24:58,998 --> 00:25:00,799 of our own biology. 445 00:25:00,799 --> 00:25:03,936 >>We know more about maybe rocks on the moon 446 00:25:03,936 --> 00:25:05,637 than what lives in the ocean. 447 00:25:10,409 --> 00:25:13,512 >>NARRATOR: Today's biomedical researchers 448 00:25:13,512 --> 00:25:16,048 are diving into the deep blue, 449 00:25:16,048 --> 00:25:20,185 hopeful the ocean's rich diversity of marine life 450 00:25:20,185 --> 00:25:25,124 will reveal answers to man's greatest health issues. 451 00:25:25,124 --> 00:25:28,694 >>One thing that's been very clear to us as marine scientists 452 00:25:28,694 --> 00:25:30,362 over the last several decades 453 00:25:30,362 --> 00:25:34,033 is that there are byproducts that we can extract 454 00:25:34,033 --> 00:25:36,301 or get from many of these marine organisms 455 00:25:36,301 --> 00:25:37,936 that can really benefit humans. 456 00:25:40,372 --> 00:25:42,608 >>It holds so much wealth for us. 457 00:25:42,608 --> 00:25:44,810 And we get our health from it. 458 00:25:46,712 --> 00:25:48,947 We firmly believe there is a cure 459 00:25:48,947 --> 00:25:51,683 down at the bottom of the sea. 460 00:26:24,783 --> 00:26:27,586 >>Major funding for this program was provided 461 00:26:27,586 --> 00:26:29,488 by the Batchelor Foundation, 462 00:26:29,488 --> 00:26:32,091 encouraging people to preserve and protect 463 00:26:32,091 --> 00:26:36,091 America's underwater resources.