WEBVTT

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>>NARRATOR:A vast expanse of liquid hope,

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the oceans are part of America'snewest medical frontier.

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Its underwater organisms areteeming with potential cures.

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>>Sponges are providing realchemicals, real pharmaceuticals.

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>>About 70% of the drugs thatwe use now have their origin

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in some natural product.

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Most of them are plant-derived.

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So can you imagine how muchmore there is

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when two-thirds of the world iscovered by water?

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The potential is unlimited.

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>>NARRATOR:The latest medical gold rush

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takes place beneath the waves.

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Marine creatures mayhold the key

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to unlocking the secretsof our own biology.

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>>The horseshoe craband its eyes

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are really quite remarkable.

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They become about a milliontimes more sensitive at night

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than they are during the day.

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>>We've used that informationto be able to get a better sense

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of how human eyes work.

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>>Aplysia fits the nichefor a basic animal

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that can be usedto study memory and learning.

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>>The compound that comes froma shallow water sponge

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can help to blockthe spread of cancer.

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>>NARRATOR: Scientists viewthis saltwater wilderness

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as a treasure chest of promisefor human medicine.

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>>I still feel like I'm a kidin a candy store,

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because marinenatural products are amazing.

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They have such potentialto really be new drugs,

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and yet we have justscratched the surface.

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>>NARRATOR:The ocean's medical mysteries

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are as deep as its trenches.

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What breakthroughs have its sealife revealed?

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Are there cures that lie beneaththe waves?

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>>Major funding for thisprogram was provided

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by the Batchelor Foundation,

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encouraging people to preserveand protect

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America's underwater resources.

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>>NARRATOR: For centuries,man has looked to the oceans

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for organic remedies toalleviate human illness.

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In 1987, a chemical isolatedfrom a Caribbean sponge

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was the first drug approved fortreatment of the HIV infection.

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Toxins from a venomouscone snail

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offer relief to those sufferingfrom severe chronic pain.

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Once again, the seasare proving to be

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a valuable resourcefor medical research.

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>>Over the last tento 20 years,

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we've been doing more and moreresearch in this environment,

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looking at the marineenvironment,

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looking at shallow waters,going into deep waters.

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And with our work,

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we're looking at thingswhich are associated

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with invertebrates.

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>>NARRATOR: In Florida,a team of scientists

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at Harbor BranchOceanographic Institute

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are testing sea sponges

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for their potentialanticancer properties.

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>>Our main focus right nowis pancreatic cancer,

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because it is the fourthleading cause of death

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of cancer in the U.S.,

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and it is one of those thatonly has a 5% survival rate.

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So that means only 5% of thepatients make it past five years

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of being diagnosed.

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So the drugs that we have rightnow are not very effective,

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and we desperately need newdrugs for pancreatic cancer.

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Normally, the way it goes, we goon the sub, you get a sponge,

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the chemists make extracts andthen we test different abilities

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that these compounds might haveto fight cancer.

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>>NARRATOR: The Center forMarine Biomedical

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and Biotechnology Researchat Harbor Branch

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houses invertebrate specimensthat have been collected

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throughout the world's oceans.

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Explorers use state-of-the-artresearch vessels

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and manned submersibles togather sea-dwelling creatures.

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>>So Harbor Branch has had theJohnson Sea Link submersibles,

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and they dive to 3,000 feet ofseawater-- or 910 meters--

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and they are fully outfittedwith a work platform

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that allows us to collectdifferent organisms.

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>>NARRATOR: Once an organismhas been collected,

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chemists break down the specimen

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and begin the processof purification.

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After an extract has beenisolated,

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scientists likeDr. Esther Guzman

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perform a series of teststo determine

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if the item shows activityagainst cancer cells.

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>>Sponges cannot do much otherthan being in their little site,

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so that makes them nice littlechemical factories,

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because everythingthat they want to do,

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whether it's grow or expand

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or attract another spongeto reproduce,

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they do this by releasing thingsinto the water.

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That little sponge,as innocent as it looks,

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it's making somevery heavy chemicals.

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If you put, for example, a dropof perfume in a glass of water,

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you're going to lose that smell.

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So think about how potentthe signals of a sponge are,

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because they are releasing itin more than a glass of water;

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they are releasing itto the sea.

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>>NARRATOR: One of these"chemical factories"

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is the Caribbean barrel sponge.

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It contains a compound calledmanzamine A,

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which has drawn a lot ofattention from scientists.

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>>We've shown recentlyit can help to block

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the spread of the cancer.

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>>If you thinkabout pancreatic cancer,

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the reason it's very aggressive

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is that normallywhen it's detected,

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it has already migratedto another organ,

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so it has already metastasized.

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Manzamine A stops that process.

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One of the characteristicsof cancer cells

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is that they don't needthis cell-to-cell interaction.

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They actually thriveon their own,

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and that might be oneof the characteristics also

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that can lead to this spreadingto another organ.

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And if you put manzamine Ain their midst at low doses,

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it kind of returnsthe cell-to-cell interaction.

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It also prevents the cellsfrom migrating

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from one organ to another.

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>>NARRATOR:In addition to manzamine A,

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another sponge extractthat shows promise

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for cancer therapies isdiscodermolide.

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Initially developedas an immunosuppressant,

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discodermolide, which comesfrom a Bahamian sea sponge,

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functions similarly to Taxol,

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a pharmaceutical commonly usedto treat patients with ovarian,

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breast or lung cancer,

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as well as patients withAIDS-related Kaposi's sarcoma.

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>>Taxol is one of the majordrugs used to treat cancer,

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and it was isolatedfrom a yew tree.

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The way Taxol worksis that it freezes

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or hyper-stabilizes tubulin.

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Tubulin is a protein that is inall your cells.

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and it helpsto give cells shape.

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It is very necessary whenthe cells are going to divide.

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When you put Taxol in a cellthat is dividing,

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the cell can no longer alignitself,

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and so these cells will die.

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There are certain tumors that donot respond to it,

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and there are certain tumorsthat become resistant to it.

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Discodermolide is aboutthe same potency as Taxol,

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but it is still effectiveon cells

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that have becomeresistant to Taxol.

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>>NARRATOR:Researchers at Harbor Branch

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are also looking for chemicalagents that can target

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malignant cells efficiently

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without suppressinghealthy body systems.

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>>One of the major problemsthat we have

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with cancer treatmentsor with chemotherapies

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is that you tendto kill normal cells

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as much as you'rekilling cancer cells.

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>>NARRATOR: A sponge foundin Bahamian waters

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contains a compoundthat may help reduce

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patient side effectsthrough cell selectivity.

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Leiodermatolide,its chemical extract,

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shows greater activityagainst cancer cells

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than healthy cells.

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>>Having this selectivity--that it kills

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6,000 times more cancer cellsthan normal cells--

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is that then you will haveless side effects,

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because in certain sensesyou are weakening the patient

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while you are tryingto kill the cancer.

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>>NARRATOR: The marine naturalproducts from Harbor Branch

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are in various stagesof testing.

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Getting drugs approved

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by the U.S. Food and DrugAdministration

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is a lengthy process,

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one that can take years beforethe public can gain access

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to novel compoundssuch as these.

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However, cancer biologistslike Dr. Guzman

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are still optimistic thatsponges will one day

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provide better medicinesto treat pancreatic cancer.

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They are living fossils.

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Horseshoe crabs arecuriously resilient

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and unassuming creatureswhose unique biology

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has captivated the interestof man for decades.

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More closely relatedto spiders and scorpions

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than to true crabs,ancestors of horseshoe crabs

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existed 350 million years ago,

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long beforethe age of dinosaurs.

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In the 1900s,

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horseshoe crabs were commonlyused in the farming industry

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as crop fertilizersand as feed for livestock.

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By the mid-1970s,

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commercial fishermenbegan using them as bait

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for eel and conch fisheries.

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But it's the crab's "blue blood"

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that revolutionizedthe medical industry.

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>>They have a special chemicalin their blood

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that's used to detectthe presence of bacterium.

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>>That bacterium assay is usedto screen everything

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that goes intoa human being and to test

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the sterility of allthe machines that are used

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to deliver such products,like IV fluids.

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>>NARRATOR:And that's not the only factor

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that makes horseshoe crabsof interest to modern science.

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Dr. Barbara Battelle fromthe University of Florida's

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Whitney Lab for MarineBioscience in Marineland

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focuses on the animal'sdistinct visual system.

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>>Well, it has ten eyes--

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two compound eyes thatare just like fly eyes.

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These are the big eyes that yousee on the sides of the carapace

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or the upper part of the animal.

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And the photoreceptorsare very large,

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among the largest in nature,so in experimental preparation,

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they're really very useful.

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>>NARRATOR:Horseshoe crabs have roughly

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1,000 photoreceptors,or light-sensitive cells,

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in each compound eye,

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compared to the millionsfound in human eyes.

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>>There are many peoplethat have reduced vision,

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and we don't havean explanation for it.

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Why is vision going down?

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How does that happen?

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Well, in mammalsit's difficult to study,

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because our eyes are complex.

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>>NARRATOR:In 1976,

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researchers fromSyracuse University discovered

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that manipulation of an opticnerve that transmits signals

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from the brain to the compoundeyes of a horseshoe crab

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mimics the visual functionof circadian clocks.

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>>Circadian clocksare internal clocks

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that we have in our cellsand in our brain

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that make us change ourphysiology, day to night.

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And we experience the effectsof our circadian clocks

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when we travelacross time zones.

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The circadian clockin your brain

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doesn't only controlyour sleep-wake cycle;

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it also controlshow our eyes work.

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>>NARRATOR: In 1967,Dr. Haldan Keffer Hartline

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and his colleagues atthe Marine Biological Laboratory

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in Woods Hole, Massachusetts,

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won the Nobel Prize for theirwork examining horseshoe crabs.

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They identifiedlateral inhibition,

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a visual processin animals and humans alike

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that enhances contrast,

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helping the eyeto see borders and edges.

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Scientists at the Whitney Lab

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hope this specieswill provide even more clues

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on the basicmechanisms of vision.

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>>Oftentimes, our circadianrhythms degrade as we age,

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and it could bethat some of the reasons

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for impaired visionas we get older

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is that the signals from thecircadian clock are degrading,

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and the cells aren't gettingthe information they should get.

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>>NARRATOR:To test this theory,

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Dr. Battelle works with livespecimens from her wet lab,

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where a skylight provides

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natural day- and night-timelight patterns.

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Tissue samplesfrom the compound eye

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are analyzed to detectany biochemical changes

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that occur in response tointernal or external stimuli.

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>>We discovered a major proteinin the photoreceptors.

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So a proteinis the part of the cell

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that actuallydoes the work of the cell.

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So we found a major protein

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that is changedin response to the signal

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from the central 24-hour clock.

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And we don't really know whatthat protein does yet,

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but we thinkit has a major impact

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on the way thephotoreceptor cells function.

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>>NARRATOR: By controllingcircadian input

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to the compound eye,

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lab tests revealedconcentrations

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of the newly discovered protein,opsin 5.

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Although similar proteins arefar more abundant

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during the night and day,

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opsin 5 molecules may stillimpact photoresponse.

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>>So we can see these proteinsactually move around.

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They're in different placesdepending on the time of day,

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and that gives us some clue

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about how the photoreceptoris changing its sensitivity,

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day to night-- clock input,no clock input, and so forth.

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So it gives us a clue of what'sgoing on inside the cell.

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>>NARRATOR: Studies indicatethat light,

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as well as the animal'scircadian clock,

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regulate opsin 5 differently

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than otherphotosensitive proteins.

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Experts suspect that changesin levels may underlie

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some the dramatic day-nightchanges in photoreceptors.

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>>The horseshoe craband its eyes

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become about a million timesmore sensitive at night

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than they are during the day,and what's really interesting

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is that we foundthe same kind of protein

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in the photoreceptorsof mammals.

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And that's the way

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the sort of comparative biologythat we do works.

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We find something in a simplerorganism, and then we ask,

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"Well, are we finding the samesorts of things

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in other organisms?"

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Basic mechanisms that go on incells, regardless of species,

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are similar.

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And as we discoverwhat this protein does

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in the horseshoe crab eye,then we can begin to ask

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more pointed questionsabout what it might be doing

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in our own eyes.

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So, if we can figureout how to make

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cells more sensitive to light,

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then the potential isthat we can fix them.

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>>NARRATOR:Marine invertebrates

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are seemingly basic organisms.

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Yet their simplistic anatomiesoffer great insights

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into the way the humannervous system functions.

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The larvae of starfish helpresearchers understand

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how the body defends itselfagainst disease.

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The mechanisms by whichnerve impulses travel

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along nerve fibers wasdiscovered via studies on squid.

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In 2000, experiments with seaslugs won Eric Kandel

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and his colleaguesat Columbia University

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the Nobel Prize in medicine

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for their workon the cellular processes

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of learning and memory.

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The National Resourcefor Aplysia in Miami

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is the only facilityin the world

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where sea slugs are raisedfor research purposes.

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>>Aplysia californicahas become an important model

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for studying the developmentof the nervous system,

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learning, behavior.

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>>NARRATOR: In 1975,Thomas Capo joined Eric Kandel

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at Columbia University,where he worked to improve

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the availability of sea slugs,or aplysia,

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for year-round studies.

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>>Aplysia are an annual animal.

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If you want to work with smallanimals in the late summer,

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you can't find them.

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Or, if you wanted to work withsmall animals in the winter,

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they're not available.

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So what we do here

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at the University of Miami'sAplysia Resources,

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we raise animalsthroughout the year.

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>>NARRATOR:Before coming to Miami,

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researchers moved toWoods Hole, Massachusetts,

19:16.922 --> 19:20.826
where originalaquacultural operations began

19:20.826 --> 19:22.928
onAplysia californica,a species commonly found

19:22.928 --> 19:26.632
on the West Coastof the United States.

19:26.632 --> 19:31.203
>>By 1978, we had movedto Woods Hole,

19:31.203 --> 19:33.472
and it's there that we madethe major breakthroughs

19:33.472 --> 19:36.742
in getting large numbers ofanimals through the larval phase

19:36.742 --> 19:38.611
and the metamorphic phases.

19:38.611 --> 19:41.681
And once we were able to growlarge numbers of animals,

19:41.681 --> 19:44.450
it became obvious that we neededa larger facility,

19:44.450 --> 19:48.120
a better facility, and there wasa major problem

19:48.120 --> 19:50.956
working in Woods Hole,and that was food supply.

19:50.956 --> 19:55.027
And in Florida,at the University of Miami's

19:55.027 --> 19:57.163
experimental facilityon Virginia Beach

19:57.163 --> 19:59.598
was the ideal place,

19:59.598 --> 20:01.467
because not only did we havean abundant supply

20:01.467 --> 20:02.902
of ambient seawater,

20:02.902 --> 20:05.071
we also had warm weatherto culture the algae.

20:05.071 --> 20:11.277
And within two or three yearsof moving here in 1989,

20:11.277 --> 20:14.280
we were able to cultureover 300,

20:14.280 --> 20:16.215
400 pounds of seaweed a week,

20:16.215 --> 20:20.786
which was necessaryto produce the animals.

20:20.786 --> 20:23.723
And also, we had an abundantsupply of raw seawater

20:23.723 --> 20:27.159
which we could clean up,chill down

20:27.159 --> 20:28.994
and grow our animals in.

20:28.994 --> 20:31.831
The facilitywas initially set up

20:31.831 --> 20:34.500
to produce around10,000 animals,

20:34.500 --> 20:36.535
but we've expandedseveral times over the years,

20:36.535 --> 20:38.337
and now we produce anywhere

20:38.337 --> 20:40.406
between 25,000 and 30,000animals a year

20:40.406 --> 20:43.175
for researchersaround the world.

20:48.280 --> 20:51.951
>>NARRATOR: One of thoseresearchers, Dr. Leonid Moroz,

20:51.951 --> 20:55.654
works at the Universityof Florida's Whitney Lab.

20:55.654 --> 20:58.524
His studies focus on howindividual nerve cells

20:58.524 --> 21:02.394
function in relationto memory and learning.

21:02.394 --> 21:04.864
>>Aplysia offersthis opportunity,

21:04.864 --> 21:07.733
because it has a relativelysimple neurosystem,

21:07.733 --> 21:11.437
with only about100 cells per ganglion

21:11.437 --> 21:15.341
and roughly 10,000 cellsin the whole brain--

21:15.341 --> 21:17.409
and, importantly,most of these neurons are giant.

21:17.409 --> 21:19.745
You can study connectionsof the cells

21:19.745 --> 21:23.015
and, most importantly, you canlink everything to behavior.

21:23.015 --> 21:25.117
>>NARRATOR:Aplysia neurons are so large,

21:25.117 --> 21:28.521
they can be seenby the naked eye.

21:28.521 --> 21:32.191
They possess nine groupsof nerve cells, or ganglia,

21:32.191 --> 21:35.327
within their bodies, distinctphysical features

21:35.327 --> 21:40.065
that help experimentalscientists view aplysia

21:40.065 --> 21:44.804
as a model organismsfor neuroscience research.

21:44.804 --> 21:47.807
>>Aplysia seem to be aninteresting approach,

21:47.807 --> 21:51.710
a reductionist approach wherebyyou look at an animal

21:51.710 --> 21:53.679
with a small number of neurons

21:53.679 --> 21:56.415
and basically getan understanding

21:56.415 --> 21:59.585
of how the nervous system works.

21:59.585 --> 22:01.754
>>If you rememberyour first kiss,

22:01.754 --> 22:04.089
more likely what would happenin your brain--

22:04.089 --> 22:06.892
or happened in your brain--is that cell A and cell B

22:06.892 --> 22:10.196
and cell C, they just talkto each other,

22:10.196 --> 22:13.766
and synapses, the connectionsbetween cells, become stronger

22:13.766 --> 22:15.901
and, more likely,they change shape.

22:15.901 --> 22:18.404
So efficiency of theseconnections becomes better

22:18.404 --> 22:19.972
or less better.

22:19.972 --> 22:23.108
So if it's better, you will morelikely remember something;

22:23.108 --> 22:25.811
if it's weaker,you will lose this memory.

22:25.811 --> 22:29.315
>>NARRATOR: Dr. Moroz examineshow aplysia neurons

22:29.315 --> 22:33.652
and synapses change as a resultof memory formations.

22:33.652 --> 22:37.823
Similar to Pavlov's famoussalivating dogs experiment,

22:37.823 --> 22:42.461
Dr. Moroz can elicit specificbehaviors from sea slugs

22:42.461 --> 22:44.597
through basic forms of learning.

22:44.597 --> 22:47.833
>>You give to aplysiaa simple task.

22:47.833 --> 22:50.502
You produce tactical stimulationwhich is associated

22:50.502 --> 22:52.738
with some kind of algaeor juice.

22:52.738 --> 22:55.074
In aplysia, you'll producea feeding reaction

22:55.074 --> 22:57.776
following this weak stimulus,which normally

22:57.776 --> 22:59.478
they do not produce.

22:59.478 --> 23:04.250
So you do, like, 40 repetitions,and aplysia will remember.

23:04.250 --> 23:07.953
So this is a sort of elementarylearning and memory.

23:07.953 --> 23:11.290
It's called associative type ofmemory, when animals associate

23:11.290 --> 23:13.826
to a type of stimulus,make connections,

23:13.826 --> 23:17.830
and basically preserve thoseconnections for quite a while.

23:17.830 --> 23:21.033
So you count the number ofsynapses between cells

23:21.033 --> 23:24.336
before and aftermemory formations.

23:24.336 --> 23:26.572
So in older aplysia,this number of connections

23:26.572 --> 23:28.741
becomes weaker,

23:28.741 --> 23:30.743
and a similar processhappens in the human brain

23:30.743 --> 23:32.845
or a variety ofneurological diseases.

23:32.845 --> 23:35.180
So everything youlearn and remember,

23:35.180 --> 23:38.517
it's really linked to how oneneuron talks to each other

23:38.517 --> 23:39.952
and how theypreserve this efficiency

23:39.952 --> 23:41.120
of these communications.

23:41.120 --> 23:44.657
So you can reducecomplex memory process

23:44.657 --> 23:47.660
to the level ofonly a few cells.

23:47.660 --> 23:49.428
In fact, many people would besurprised

23:49.428 --> 23:51.997
how many neurons would needto form

23:51.997 --> 23:54.867
elementary forms of memory;only three cells is sufficient.

23:56.035 --> 23:59.138
>>NARRATOR: By studyinglearning and memory

23:59.138 --> 24:01.607
at the cellular level, Dr. Morozhopes his experiments

24:01.607 --> 24:06.445
will one day lead to solutionsfor neurodegenerative conditions

24:06.445 --> 24:10.215
such as Alzheimer'sand Parkinson's diseases.

24:10.215 --> 24:12.484
>>I bet if you will solvethe problem--

24:12.484 --> 24:15.921
how in aplysia two neurons talkto each other,

24:15.921 --> 24:19.325
how they modify the synapses--it will be one or another way

24:19.325 --> 24:23.362
to apply it to clinical studiesor disease analysis.

24:30.836 --> 24:34.673
>>NARRATOR: Scientists say itis important to study

24:34.673 --> 24:36.542
a diverse group of species

24:36.542 --> 24:39.979
to better understandcomplicated processes.

24:39.979 --> 24:42.948
>>If everybody looked justat a rat or a mouse,

24:42.948 --> 24:45.050
we'd know a lotabout a rat or a mouse,

24:45.050 --> 24:47.319
but we wouldn'thave the full spectrum

24:47.319 --> 24:49.488
of understanding about biology.

24:49.488 --> 24:53.826
But by studying these simpleror less complex organisms,

24:53.826 --> 24:55.928
we can learn a lotabout basic processes,

24:55.928 --> 24:58.998
and I think that remainscritical to our understanding

24:58.998 --> 25:00.799
of our own biology.

25:00.799 --> 25:03.936
>>We know moreabout maybe rocks on the moon

25:03.936 --> 25:05.637
than what lives in the ocean.

25:10.409 --> 25:13.512
>>NARRATOR:Today's biomedical researchers

25:13.512 --> 25:16.048
are diving into the deep blue,

25:16.048 --> 25:20.185
hopeful the ocean's richdiversity of marine life

25:20.185 --> 25:25.124
will reveal answers to man'sgreatest health issues.

25:25.124 --> 25:28.694
>>One thing that's been veryclear to us as marine scientists

25:28.694 --> 25:30.362
over the last several decades

25:30.362 --> 25:34.033
is that there are byproductsthat we can extract

25:34.033 --> 25:36.301
or get from manyof these marine organisms

25:36.301 --> 25:37.936
that can really benefit humans.

25:40.372 --> 25:42.608
>>It holdsso much wealth for us.

25:42.608 --> 25:44.810
And we get our health from it.

25:46.712 --> 25:48.947
We firmly believethere is a cure

25:48.947 --> 25:51.683
down at the bottom of the sea.

26:24.783 --> 26:27.586
>>Major fundingfor this program was provided

26:27.586 --> 26:29.488
by the Batchelor Foundation,

26:29.488 --> 26:32.091
encouraging people to preserveand protect

26:32.091 --> 26:36.091
America's underwater resources.