BIOTECHNOLOGY & YOUhardmanenvsci.weebly.com/uploads/5/2/0/5/5205206/yw-72...Alan Gardner, SmithKline Beecham Anthony Green, Puresyn, Inc. Mary Ann Mihaly Hegedus, Bioprocessing Resource

Volume 7, Issue No. 2

BIOTECHNOLOGY & YOU

a magazine of biotechnology application in healthcare, agriculture, the environment, and industry

Diving IntoMarineBiotechnology

2 Marine Biotechnology

BIOTECHNOLOGY & YOU

C O N T E N T STABLE OF

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Volume 7, Issue No. 2

Your World/Our World describes the application ofbiotechnology to problems facing our world. Wehope that you find it an interesting way to learnabout science and engineering.

Development by:The Pennsylvania Biotechnology Association,The PBA Education Committee, andSnavely Associates, Ltd.

Writing & Editing by:The Writing Company, Cathryn M. Delude andKenneth W. Mirvis, Ed.D.

Design by:Snavely Associates, Ltd.

Illustrations by:Patrick W. Britten

Science Advisor:Judy Brown,University of Maryland Center for Marine Biotechnolgy

Science Reviewers:Dr. Rita Colwell, Dr. Shaojun Du, Dr. William Jones,Dr. Dennis Maeder, Dr. Allen Place, Dr. Frank Robb,Dr. William Straube, Dr. John Stubblefield, Dr.Yonathon Zohar (University of Maryland BiotechnologyInstitute’s Center of Marine Biotechnology)

Special Thanks:The PBA is grateful to the members of theEducation Committee for their contributions:

John C. Campbell, SmithKline Beecham

Kathy Cattell, SmithKline Beecham

Ceil M. Ciociola, PRIME, Inc.

Jeff Davidson, Pennsylvania BiotechnologyAssociation

Alan Gardner, SmithKline Beecham

Anthony Green, Puresyn, Inc.

Mary Ann Mihaly Hegedus, Bioprocessing ResourceCenter

Linda C. Hendricks, SmithKline Beecham

Daniel M. Keller, Keller Broadcasting

Richard Kral

Colleen McAndrew, SmithKline Beecham

Barbara McHale, Gwynedd Mercy College

June Rae Merwin, The West Company

M. Kay Oluwole

Lois H. Peck, Philadelphia College ofPharmacy & Science

Jean L. Scholz, University of Pennsylvania

John Tedesco, Brandywine Consultants, Inc.

Adam Yorke, SmithKline Beecham

Laurence A. Weinberger, Esquire,Committee Chair

If you would like to make suggestions or commentsabout Your World/Our World, please contact us at:Internet: [email protected] write to:Pennsylvania Biotechnology Association1524 W. College Avenue, Suite 206State College, PA 16801

Copyright 1998, PBA. All rights reserved.

Exploring the Diversityin the Sea

46

The Biotechnology Porthole

The Ocean Superstore

8 Zippy Zebras

10 Fertile Turtles

Life at the Extremes

14 Sunny Jiang: PredictingCholera Outbreaks

15 Taking it to Extremes!

On the Cover: Deep-sea submersible vessels like the Alvin help us explore the diverse life formsbeneath the sea. This and other modern technologies help us study our marine world, combiningresearch, conservation, and education to understand and protect our earth’s precious natural resource,the ocean.

A C T I V I T Y

12P R O F I L E

Marine Biotechnology

16 Resources

Credits:Cover image, JASON Foundation for EducationPage 10, Copyright © 1930 by Ogden Nash Reviewed, reprinted, by permission of Curtis Brown, LtdPage 13, Reprinted from Journal of Molecular Biology, Vol 270, Figure 10, Lim J-H, Yu Y, Han Y, Cho S, Ahn B, Kim S, Cho Y, “The crystalstructure of an Fe-superoxide dismutase from the hyperthermophile Aquifex pyrophilus at 1.9 Å resolution: structural basis forthermostability” pp259-274 (1997), by permission of the publisher Academic Press Limited.

Your World Our World 3

EX

P L ORIN G T HE DIVERSITY INTHE SEAEX

P L ORIN G T HE DIVERSITY INTHE SEA

Question:What has the oldest, most numerous, most diverse, andleast studied life forms on earth? What covers almost three-fourths of our planet but is our greatest untapped resource?Where do creatures thrive in temperatures of 121°C(250°F)? What could provide food to the starving peopleof the world but is having its supplies endangered by over-

harvesting and pollution?Answer: The sea, the sea, the beautiful,

mysterious sea.

The sea remains mysterious because it is so hard toexplore. It is wide, deep, and dark, with dangerous

waves and icebergs on the surface and incrediblyhigh pressures below. The ocean floor hasmountains, canyons, and volcanoes, where

temperatures range from below freezing to aboveboiling. Exploring these areas was impossible untilwe developed technologies such as deep-seasubmersibles, scuba, sonar, lasers, videos, andsatellites. Still, studying marine biology remains achallenge because so many creatures live in strange,inaccessible places, and we can’t keep them aliveand thriving in the artificial conditions of a surfacelaboratory. Because of these difficulties, we haveprobably catalogued fewer than 5% of marineorganisms, much less studied them in depth.

Fortunately, biotechnology opens a anotherwindow on marine life. It allows us to inspectorganisms at a molecular and genetic level– and to do so quickly, beforehuman activity reduces theincredible biodiversityof life in the sea.

Why is this study so valuableto us? Scientists have alwaysfound useful productsproduced by living plants andanimals. The ocean environ-ments are completely

different from our own, and marine creatures probablyproduce a whole different set of useful products – a treasurechest full! Now researchers are looking to the sea foreverything from a cure for cancer and AIDS to less-pollutingindustrial chemicals, and much, much more.

We are also improving our knowledge of the world atlarge by studying marine creatures. The

microscopic life in the sea holds clues to theorigin of life on earth – and to global cycles of

oxygen, carbon, and nitrogen. Furthermore,we share many genes with marine organ-isms, so we can learn about ourselves by

studying them. What helps them stayhealthy may also help us. Likewise, whathurts them may harm us.

This issue of Your World/Our World showshow biotechnology is making the mysteri-ous sea more understandable and useful to

us, while also allowing us to protect itsprecious resources. So put on yoursnorkel and mask, and dive into ourunderwater biotechnology laboratoryto explore this last earthly frontier.

Biotechnology helps us study thediverse and beautiful creatures ofthe sea.

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Biotechnology and molecularbiology can shed light on theinnermost life processes of

the organisms that live in the sea’sdeep, dark, inhospitable places. Hereare a few techniques that give us apeek through that porthole.

Proteins and EnzymesAll organisms produceproteins to build cells andperform the functions oflife. Certain proteins,

called enzymes, carry outbiochemical processes within cells.

Top to bottom, left to right

Coral Reefs are to the sea what tropical rainforests are to the land: teeming with speciesthat may have medicinal value, yet vulnerableto destruction by human activity.

Puffer Fish secrete a deadly poison thatscientists use to study neuromusculartransmission in people.

Striped Bass could help feed a hungryworld. But they are declining in the wild, andthey are hard to breed in fish farms. Geneticresearch may overcome these difficulties.(Pages 8 –9.)

The Sea Sponge has defense mechanismsthat could someday help you reduceinflammations, fight bacterial and fungalinfections, and perhaps cure cancer.(Pages 6 – 7.)

Sharks live in a microbe–infested world,sothey secrete a steroid disinfectant that killsgerms on contact. Some sharks contain asubstance “squalamine” that cuts off theblood supply to tumors and is being testedfor treating cancer.

Crabs and Shrimp have molecules withmany uses in every day life and science.(Page 7.)

Sea Turtles are exposured tochemicals that may interfere withtheir egg development. Thesechemicals may harm mammals as well.(Pages 10 – 11.)

The Squid’s nerve axons serve as a modelsystem in neuroscience.

Submersible Vessels help us explore thedeep and collect samples for further study.We can also learn about past climatesand geological events on earth.

Thermophiles thrive near thevolcanic heat of these deep-sea vents,and we might be able to use theseunusual organisms for medicine andindustry.(Pages 12 – 13.)


Scientists are studying theseand other organisms for theirscientific and medical value.


assembling proteins. Variations inthat gene provide a yardstick forhow closely organisms are related.This yardstick gives us a newpanoramic view of the world’s“family tree.” It also gives us ashortcut to identifying unstudiedmarine organisms and screeningthem for useful products.

PCR (polymerasechain reaction)

Single fragments of DNAare too tiny to manipu-

late in the laboratory. Theyneed to be amplified just as

a stereo needs an amplifier tomake a sound signal loud enough tohear. PCR is a way of making manyexact copies or clones of a tinysectionof DNA, which can be used forfurther research.

Fermentation Scientists can insert a gene

that produces a valuablemarine protein into the

DNA of an easy-to-growbacterium like E. coli

or a yeast cell. These “workhorse”microorganisms then reproduce infermentors and act like mini–factories, churning out the protein.Fermentation allows us to producethe valuable natural products evenwhen we cannot grow the wholeorganism – or when we do not wantto harvest proteins from a rarecreature living in a fragile marineecosystem.

AntibodiesWhen a bacterium or

virus invades your body,your immune systemproduces an antibody thatlatches onto that microbe to

destroy it. Scientists use antibod-ies to “see” a hard-to-detectmarine microbe: They tag theantibodies with special labels thatidentify the microbes when theantibodies lock onto their target.

We use the proteins and enzymes asingredients in everything frommedicines to soap. Analyzing theirchemistry teaches us about theirroles in the organism’s biology – andtheir potential benefits to us.

DNA and GenesDNA is the informa-

tion molecule that tellseach organism how to

develop, giving each cell itsspecial characteristics. DNA

forms genes, which are sequences ofcodes that “spell out” the recipes forproteins. We can learn about aprotein by analyzing its DNAsequence. In addition, we can studywhich genes become active inresponse to a threat from a predator,or a change in temperature andnutrients, or pollution. By trackingthe molecular activity of marineorganisms, scientists can study theirinteraction with the environmentand gain insights into changes inglobal climate and pollution.

Classification We classify organismsto tell how they arerelated to each other.Scientists used to focuson how organismslooked. If they lookedsimilar, they were

probably related. Genetic compari-son gives us more accurate classifi-cations. It relies on the fact that allorganisms share some commongenes, such as a gene involved in


Swim through this

porthole to see

how scientists use

these techniques

to stock the

shelves of the

ocean superstore

on the next page!


SuperstoreSuperstore

These two venomous animals can wound or even killhumans, but their poison also contains ingredients thatcan heal us. Doctors are already using bloodpressure medication derived from the rattlesnake’spoison. Scientists are developing a blood-clottingmedication from proteins contained in the conesnail’s venom to treat hemophilia.

This sea sponge (Cliona Celata) is just one of manymarine organisms that produce proteins and othermolecules that may fight inflammation, infection,and even cancer.

Welcome to the ocean superstore, the showcase of many present andfuture products made from marine life. Most of these items weren’tactually taken directly from the sea. Rather they were, or will be,“inspired” by products found in the sea.

their preda-tors. Theydefend themselvesby producing bad-tastingor toxic chemicals. Scien-tists tested this hypothesis bystudying the sponge’s slimy secre-tion. Sure enough, it contains toxinsthat drive predators away – as wellas a chemical that reduces inflam-mation in people. This chemicalprevents the release of an “arachi-donic” (ah-rak-id-on-ik) acid thatplays a key role in the biochemicalprocesses of pain and swelling.Aspirin also works by disrupting theproduction of this inflammatoryacid. Scientists are adapting thechemical to develop new anti-inflammatory ointments for treatingbee stings, poison ivy, arthritis,psoriasis, and gout.

Scientists also test the products ofmarine organisms to see if they stop

infections, strengthen or weaken theimmune system, or fight cancer.They are looking for clues to treatdeadly infectious diseases such asAIDS, Ebola, and drug-resistantforms of tuberculosis.

As you can imagine, searchingfor new medicines in the vastocean could take forever if yousimply followed nature’s clues.Fortunately, genetic screen-ing gives scientists a faster,more precise way to search.

Suppose you find a species thatproduces a weak anti-cancerprotein. Perhaps one of its cousinsmight produce a more potentprotein. How can you find thatcousin? In the old days, you wouldcompare their physical structures.Today, you compare their genes.The more similar the genes are, themore likely they produce a productwith similar functions. Computerscan analyze millions of genes andtarget species with anti–cancerproteins. In this way, you can screenthousands of species to find the fewthat may be worth studying further.Scientists expect these methods willspeed up our search for new medi-cines from the sea – and fill thepharmacy shelves.

The Ocean

Superstore

The Pharmacy AisleOur oldest medicines were leaves,flowers, and barks, and manymodern drugs come from suchnatural products. Organisms produceproteins, hormones, starches, andother chemicals to help them survivein their environment. These productsoften have a different effect in humanbeings. For example, the rattlesnake’spoison contains chemicals that lowerblood pressure in people. Until now,most products used for drugs camefrom the land rather than the sea.But that may soon change.

How do you find new medicines inthe sea? One way is to follow cluesof nature. For example, scientistsnoticed that a sponge from the coralreefs of the Pacific, Luffrariellavariabilis, looks good enough to eat,but predators leave it alone. Maybethe sponge uses the tricks of landplants which can’t run away from

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GRIND & FIND

Marine biologist Bill Jones explains how bacteriumacinetobacter helps clean up oil spills and degreasethese shoe parts after they are taken from their molds.

The Cleaning AisleCheck the labels of the soaps anddetergents in this aisle. Most of themlist surfactant as an ingredient. Asurfactant reduces the surfacetension of the water at the dirt’ssurface, loosening the dirt so it canbe washed away. Certain organismsproduce natural soaps calledbiosurfactants. One marine microbenamed Acinetobacter put on a greatshow following the 1989 ExxonValdez oil spill off the Alaskan coast.Its biosurfactant loosened the oilfrom the sand and rock so thebacteria could break down the oil.Now, Acinetobacter is grown com-mercially to help clean up oil spills.It also has a potential job in anotherindustry. The Nike shoe factorycoats the molds for its running shoeswith an oily compound so the plasticshoe parts won’t stick. Afterwards,the parts have to be cleaned. Ratherthan using chemical solvents todissolve the grease, the company isexperimenting with Acinetobacter,the environmentally friendlycleaner-upper.

The All-Purpose AisleMany of the foods and drugs in thissuperstore contain additives derivedfrom shellfish. Their shells contain along molecule called chitosan (kite–o–san) that is a kind of starch orpolysaccharide. Chitosan is amolecule of many uses. It acts as agel and thickening agent in foods like

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ice cream. It draws out impuritiesfrom substances, so it helps purifymaterials in research laboratoriesand treat drinking water. It absorbsfat, so it is used in alternative dietmedicines. New research shows itbreaks down the barriers betweencells in the stomach and intestines,so it may be used to help your bodyabsorb medicines more completely. Itgets inside cells, so it may become adelivery vehicle for gene therapy,taking “repair” genes into a cell’s

Mollusks helped cloakthe ancient Phoeniciansin their royal purplerobes, thanks to a dyederived from their slime.

DNA. It may also create a new type ofadhesive that hardens under water.Dentists could usesuch anadhesive onbraces andto glueteeth backinto the jawafter beingknocked out!

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Biotechnology allows us to sample and test huge numbers ofmarine organisms for useful products. Scientists then reproducethose products synthetically rather than harvesting them directlyfrom the marine environment. Here’s the process for searchingfor medicinal proteins:

Extract theproteinsproduced byeach organismthat is sampledusing a physical(perhapsgrinding) orchemicalprocedure.

Test the proteins to seeif they show activityagainst cancer cells,inflammations, and/ormicrobial infection.

Identify the genes that encode the active proteins, and search forother organisms with similar genes. Repeat steps 1 and 2 until themost effective protein is found.

Take a copy of the gene for the most effective protein and insertit into “workhorse” organisms. These workhorses then producethe protein when they are grown in large numbers. The proteinsare grown first in a small flask, then the whole process is “scaledup,” and the proteins are grown in huge fermentation tanks.

Purify the active proteins from the fermentation process andprepare them into a final product.

Thousands of organisms are tested as in steps1 & 2, but VERY FEW go through steps 3-5.


Fish for a LifetimeAn old saying goes, “Give people a fish and theycan eat for a day. Teach them to fish and they caneat for a lifetime.” As the world’s populationgrows larger, the saying rings truer than ever. Fishprovide a healthy, nutritious meal, but the oceanis so overfished that many nets come up empty.Pollution in the coastal waters where fish spawn(breed) has also reduced the supply of fish.Luckily, the aquaculture “fish farm” industry hascome to the rescue, breeding food fish in captivityto increase their supply. Unfortunately, onepopular and nutritious food fish – the striped bass– does not like life in the fish farm. It won’t spawn

in captivity.

Scientists are learning whynot by studying thezebrafish. This little fishzips around many house-hold freshwater aquari-

ums. The zebrafish is easy to breed in captivityand matures quickly, so it provides a wonderfulmodel for studying both fish reproduction anddevelopmental biology. Now it is also helping tosolve the striped bass’s reproductive problems“down on the farm.”

Model Species: Different Stripes,Similar GenesThe zebrafish and the striped bass havedifferent stripes, sizes, and life spans. Still,they are genetic cousins. They start outtraveling the same developmental path,controlled by similar genes.

All vertebrates, from fish to humans, have aremarkably similar early development. That’s

because we all have an almost identical set of “mastergenes” that govern early development. Scientists call thesemaster genes homeodomain genes because they all sharea very similar region, the homeodomain, in their se-quences. (“Homeo” means “same” in Greek, and a

“domain” is a kind of home). You can think ofhomeodomain genes as highways with toll

booths. The highways (genes) aredifferent, but they have an

almost identical tollbooth section

(homeodomainregion).Homeodomaingenes worklike an electri-cal circuitbreaker in ahouse,

controlling theaction of other genes

further down the line.

One set of homeodomain genescontrols the reproductive

pathway. As speciesdevelop along thispathway, they acquiredifferent reproductivecharacteristics. Fish

spawn, birds lay eggs in a shell, and mammals have livebirths. Among fish species, further differences appear inthe reproductive wiring. Somewhere down that reproduc-tive circuit is a gene that gets switched off when a stripedbass lives in captivity.

Marine biologistErnest E. Just wrote a

land-mark work on fishembryology in 1939.

The U. S. Postal Servicehas honored Dr. Justwith a commemora-

tive stamp.



Scientists are trying to coax thestriped bass to reproduce in captiv-ity. If they can isolate the gene thatswitches off in the striped bass, theycan transfer that gene into thezebrafish. By observing how thatgene affects the zebrafish, scientistswill learn more about how it behavesin striped bass.

Scientists already know that incaptivity the striped bass does notrelease enough of a hormone,which is a molecule that acts like a

What advantagedoes aquaculturehave over live-stock farming for

the environmentalresources of a

country? Consider the land,water, and feed required toraise farm animals, and theorganic waste produced.

THIN

K

ABOUT THIS!!

Crabby DetectivesAmericans are eating moreseafood these days. Naturally, theseafood industry has growndramatically – and sohas seafood fraud.Some merchantsmisrepresent commonfish for moredesirable,higherpricedones orthey call soy-based products“crab meat.”Others sell illegalseafood, such as whalemeat. Now, the same technologythat brought DNA fingerprintinginto the courtroom can help foodinspectors detect the deception.They can take samples of theseafood, extract its DNA or theproteins encoded by the DNA, andfind out what species it really is.Once again, biotechnology helpsfight crime and protects the aver-age citizen!▼

Within these look-alike

embryos, homeodomain

genes program the cells

for increasingly specialized

roles in developing tissues.

As these tissues specialize,

species become distinct

from each other.

Fish

The aquaculture industry hastransferred genes into fish to makethem grow bigger than normal, tosurvive in waters colder than theirnatural habitats, and to resistdisease. Scientists keep them in aclosed system so they won’t breedwith wild fish. What might happen ifthe fish escaped their farms? Is thisa risk worth taking in order toprovide more food for the world?

k

Human

messenger in the body. Thisparticular hormone signals repro-duction, so without enough of it,the fish does not breed. Now thatscientists know more about thegene that encodes that hormone,scientists know more about thegene that encodes that hormone,they can mimic its function byincreasing the hormone level inother ways. They are also trying tomake striped bass spawn at anearlier age, and even to spawn yearround instead of just once a year.

Eventually, scientists hope totransfer the zebrafish’s naturalswitch gene into the striped bass totry to correct the reproductiveproblem from the start. Splicing thezebrafish gene into the site that gets“shut down” in captivity may allowthe remaining reproductive circuitryto function as normal. If theseefforts succeed, the world will have amuch more dependable supply ofhealthy, nutritious food fish.


Sea turtles have to be clever to befertile – so their species willsurvive. The hatchlings leave theirnests on the sand and waddle intothe waves to spend their lives atsea. When it’s time for the femaleto lay her average “litter” of over100 eggs, she returns to herbirthplace and builds a nest.

Trouble in the NestThings have gotten tougher for theturtle in recent years. Often, thefemale returns to her birthplace tofind a house nearby, an RV racingalong the sand, and pollution pouringinto the sea. Together, these obstaclesput many species of turtles in astruggle for survival. To makematters worse, the sex ratios ofturtle hatchlings may be out ofbalance. There are notenough males! Why not?

Research on the diamondbackterrapin is shedding light on thismystery. Sea turtles and terrapins aredifferent species, but they are similarenough that scientists can useterrapins as a model to understandsea turtles better.

Mother Nature’s EnzymeWhen the temperature in thediamondback terrapin’s nest isabove 30°C, all the hatchlingsusually become females. Below27°C, they will all be males. (Thenests in the middle temperaturerange produce a mix.) Highertemperatures switch on a gene thatproduces an enzyme calledaromatase. Aromatase converts amale hormone (androgen) into thefemale hormone estrogen. Estrogentells the embryo to develop ovariesand become female. At coolertemperatures, the gene foraromatase is not switched on, so noestrogen is produced, and theembryos develop into males.

However, scientists found that somenests kept at the cooler temperatureare producing females instead ofmales. To find out why, they coatedsome eggs in cool nests with estro-gen. The eggs absorbed the estrogenand developed into females. Eventhough the embryo cells did notproduce their own estrogen, theestrogen from the outside “environ-ment” had the same effect as naturalestrogen would have had.

Thus, changing the estrogen levelsin the embryos overrides thenatural temperature control that

The diamondback terrapin almost became extinct inthe early 1900s because it made such a tastygourmet soup. Now it is swimming in a soup of man-made chemicals. It spends its life in estuaries wherefresh water from rivers and streams mixes withseawater. Most of these rivers and streams carrypollution, so the diamondback is exposed to morechemicals than animals that live in the open ocean.

Fertile

The turtle lives ‘twixt plated decks,

which practically conceal its sex.

I think it clever of the turtle,

in such a fix, to be so fertile.

by Ogden Nash

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TurtlesTurtles


scrambling is especially bad inembryos, since fetal cells areextremely sensitive to the signalsthat tell them how to develop. Inturtles, the effect is powerful enoughto override the temperature control,producing too few males.

The Human ConnectionWhy should you care about theturtle’s fertility problems? Well,you may care about the survival ofendangered species. If therearen’t enough males, the turtles

will soonbecomeextinct.

But the turtle’stroubles may

hit closer tohome. Other species

are exposed to the same chemicalsin the environment. In our mam-mal cousin, the otter, the malereproductive organs decrease insize as the concentration ofpesticides in their bodies in-creases. Perhaps these chemicalshave overridden a mechanism inthe development of otters. If so,could they be affecting othermammals? Some scientists suspectthat human sperm counts havedeclined worldwide because ofthese chemicals. Research intothese issues continues, and youcan follow their development inthe news.

One thing is clear: Biotechnologyand molecular biology can help us

determines sex. Some scientists fearthat pesticides and other chemicalsin the environment may be jump-starting the estrogen reaction in thesame way.

Chemicals Mimicking HormonesHormones are shaped like keys thatcan lock into a keyhole or receptoron the cell membrane. When ahormone locks into the receptor, itcan send a message inside to theDNA. This message tells the DNA toturn on a certain gene, like turningon an ignition key to start an engine.It so happens that many human-made chemicals have a very similarshape to the estrogen molecule, sothey “mimic” estrogen in a cell.There are at least 50 such chemicalsthat mimic estrogen. They are usedin everything from agriculture to

making plastic andpaper, so they arejust abouteverywhere in the

environment.These chemicals

accumulate in animal tissue, wherethey can scramble the geneticinstructions for the cells. This

The debate about globalwarming is really heating up! Ifworld temperatures really arerising, how might turtles beaffected?

WhAt if?

The Dooming of a Species

We use so many products in our dailylives that contribute to estrogen-mimicking chemicals in the environ-ment: paper, plastic, garden prod-ucts.... In addition, livestock is oftengiven estrogen to stimulate growth,and we absorb that estrogen whenwe eat meat. Do the benefits we getfrom these products outweigh theharm we might be doing to otherspecies and ourselves?

understand how ourbodies react tohormones andchemicals at amolecular level.Scientists have

developed systems of cells thatproduce the same response tohormones as a whole organism.They can use these systems to testthe effects of chemicals in theenvironment. By studying howturtles are affected, we may find outhow to protect them – and the worldat large – from the onslaught ofestrogen-mimicking chemicals.


I'm gonna be a

boy!Uh, oh!

Who will I mate with?

90 days later . . .Hey, we're ALL girls!30˚C

27˚C I'm gonna be

a boy!

Below 27˚C, the embryos do not produce estrogen and should become males.

Estrogen-mimicking chemicals from the environment override the temperature control gene,

so the embryos become female.

Without enough males, the species cannot survive.


Extr

emes

cal bonds join these amino acidstogether into a three-dimensionalshape, which allows the enzyme tointeract with cells and molecules.Thus, the enzyme’s function de-pends on its structure. Extremeconditions, such as high tempera-ture, acidity, or alkalinity, can breakthe bonds that stabilize an enzyme’sstructure. When this happens, theenzyme no longer functions andmay even fall apart. Enzymes fromextremophiles, however, continuefunctioning partly because theyhave extra stabilizing bonds to holdthem together.

This difference has great commer-cial significance, since we useenzymes to promote chemicalreactions for industrial and com-mercial applications. For example,enzymes help convert corn syrup tosugar for soft drinks and improvethe cleaning power of laundrydetergents. Unfortunately, manyenzymes stop working in theextremes of industrial processes.But the extremophile enzymes,outfitted with their extra-stablechemical bonds, keep ongoing ... We learned just how usefulthe durable enzymes can be fromthe very first extremophile to bediscovered, a thermophile that livesin the hot pools of YellowstoneNational Park.

Hot Bugs in YellowstoneNo one thought it was possible fororganisms to survive in boilingtemperatures until a very surprisedscientist discovered the bacteriumThermus aquaticus (for “hot water”)

Come aboard a submersible aswe sink into the freezingwater toward the ocean floor.

Our lights cut through the blacknessand shine on weird creatures thatget their energy from minerals in thewater rather than sunlight. Up aheadlooms a steaming chimney, spewingout sulfuric liquids from volcanicactivity within the earth’s crust.

Inside the chimney walls, where it is121°C (250°F) and the pressure is200 times that at sea level, somemicrobes contentedly eat sulfurwhile others give off methane gas.How do they keep from gettingcooked, not to mention crushed todeath? And why do they choose tolive there?

In fact, they like these conditions andwould die in less extreme environ-ments like our own. Indeed, theirenvironment probably resembles ourplanet when life first began millionsof years ago. We call microbes thatstill live in such extreme conditionsextremophiles. The Greek word“philo” means “lover”. The ones thatlive in these hot vents are thermo-philes. (“Thermós” means “hot”in Greek.)

Extra-Stable EnzymesExtremophiles may be very useful tous because they produce enzymesthat act as “survival suits” againstextreme conditions.

All enzymes consist of buildingblocks called amino acids. Chemi-

“Black Smoker” and Tube Worms. The mineral rich, super-heated water that spews out of deep-sea vents formschimneys and supports many colorful creatures and hearty“extremophiles.”

Life at the

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A bacterial mat at a Yellowstone hot pool teems withthermophile organisms.

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Thesame

volcanicforces form

the Yellowstonehot pools and

deep-sea vents,and the same extremo

-philes live in both places.Thus, although the hot pools

are not marine (ocean water),marine biologists use Yellowstoneas an extremophile laboratory

because it is so much moreaccessible thandeep-sea vents.

living in a Yellowstone hot poolin the 1960s. Today, this “hot bug” isquite a celebrity. One of its enzymesis used to sustain a chemical reactionthat happens naturally in cells: thereplication or copying of DNA. A celluses an enzyme called “polymerase”to copy the DNA. Scientists wereusing the polymerase from anordinary bacterium to copy DNA inthe laboratory. To do so, they heatedthe DNA sample over and over tomake copies in a process calledthermal cycling. However, theenzymes only made one copy andthen stopped working because the

heat brokedown theirstructure.More enzymeshad to beadded for eachcycle, so the

ArchaeaMany extremophiles belong to abranch of life called Archaea. Theword “Archaea” comes from thesame root as “archaeology,” whichis the study of ancient things.Scientists think that Archaea are soancient that they evolved when theearth as we know it was stillforming. But we did not knowArchaea existed before scientistsstudied the Yellowstone hot pools.Once people began to look forsuch life forms, however, they foundthem everywhere, not just inextreme environments. In fact,Archaea may be the most commonorganisms in the ocean.When Archaea were first discov-ered, scientists did not agree onhow to classify them. Biotechnologysolved the dispute. Analysis of theirgenes showed that about one halfof their genes are completelyunknown to us. Many of theseunusual genes probably build theirsurvival suits for their extremeenvironments. ▼

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ABOUT THIS!!When you dive tothe bottom of apool, you feelpressure inyour ears. How

can you scubadive so much deeper withoutruining your ears?

The deep-sea vents occur wherewater comes in contact with hotmagma beneath the earth’s crust.The hot water dissolves mineralsand metals, mixes with gases, andbursts to the surface. The dissolvedmetals precipitate as they meet thefreezing water of the ocean, formingchimneys. These chimneys are goldmines, containing gold, silver, andother precious metals. Somecountries would like to mine thesechimneys for their metals. Butmarine biologists claim thegenetic value of theextremophiles around thesevents is worth more than theirweight in gold. Is it worthendangering the ecosystemthat could prove sovaluable tomorrow to gainwealth today?

Marine biologist Judy Brown collects samples from ahot pool in Yellowstone.

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Superoxide dismutase from Aquifer pyrophilus. Redblue colors show bonds that hold the enzymetogether at temperatures up to 100oC.

Superoxide dismutase from Mycoplasm tuberculosisthat is unstable even at 70oC. There are far fewer ofthe red and blue bonds holding the enzme together.

process was quite slow and expen-sive. Today, scientists use thepolymerase from T. aquaticus, whichkeeps working through repeated heatcycles and quickly produces millionsof copies of DNA. This technique,called “PCR” or the “polymerasechain reaction,” has automated DNAreplication and revolutionized all

areas of biotechnology and geneticresearch.

Scientists are studying thestructure of otherextremophile enzymes tolearn more about theirunique properties. Theyhope to find other

amazing applicationsthat will bring more

technologicalbreakthroughs.For example,extremophilescan protectand repairtheir DNAfrom heat andacid. Perhapstheir enzymescan be tailored

to protect us fromDNA damage caused by toxicpollutants, radiation, and otherharmful elements. This protectioncould prevent cancer and otherdiseases. So now, when scientists go“shopping” for new genes to developmedicines and industrial products,they check out the “catalog” ofextremophile genes and proteins,and they look to the oceans!

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14 Marine Biotechnology14 Marine Biotechnology

Pro

file

:Sunny Jiang

Sunny Jiang uses biotechnology to understand therelationship between cholera outbreaks and weatherpatterns. In her spare time, she trains for marathons.

Sunny became interested inmarine science when she wasin middle school in China.

“We lived on a harbor and I lovedthe beauty of the animals and theblue colors of the sea water,” Sunnymuses. She planned to major inmarine environmental science incollege. However, her parentswanted her to become a doctor, soshe studied pre-medicine with amajor in biochemistry at the NankaiUniversity in Tainjin. “In China it istraditional for parents to influencethe career choices of their children,”Sunny laughs. “But I still wanted tofollow my dream, so I accepted agraduate fellowship at the Universityof South Florida.”

Sunny earned her Ph.D. and nowworks in a research laboratory at theUniversity of Maryland BiotechnologyInstitute’s Center of Marine Biotech-nology. This research team usesbiotechnology to study how globalweather patterns such as El Niñocontribute to the spread of cholera.Cholera is a life-threatening diseasecarried by a waterborne bacteriumVibrio cholerae. Cholera outbreaksoften occur during the summer inareas near stagnant estuaries (bays).The El Niño weather pattern distrib-utes more warm, moist air aroundthe globe, affecting the circulationand temperatures of estuary waters.These changes may increase thenumbers of V. cholerae and makethem more deadly.

“People might not know that thecholera bacterium is in their wateruntil the disease strikes,” Sunnyexplains. “That’s because it’s hard todetect using standard water quality

tests. Sometimes the bacterium willnot grow in cultures, so laboratoriescannot detect it. Also, many strainsdon’t carry the form of the gene thatcauses disease. So even if we detectthe bacterium, we still don’t know if itwill cause disease. Luckily, we can usebiotechnology to overcome theseproblems.” In one method, thescientists run water through a filter tocollect all the bacteria. They attachspecially tagged V. cholerae antibodiesthat allow them to detect that bacte-rium in the water. Then, they usePCR and other techniques to analyzethis bacterium to see if it is a disease-causing strain.

Sunny’s team studies samples of V.cholerae collected from outbreakareas around the world. They isolateand culture disease-causing strains ofthe bacterium and compare theirgenetic structure to strains in otherareas. This analysis may show that adisease-causing strain is moving intoa new area. “If it is, we can warn thepeople there to take preventivemeasures, such as boiling or filteringtheir water,” Sunny explains. “We’realso trying to link the presence of V.cholerae in water samples withchanges in the water’s characteris-tics, such as its salinity, temperature,and levels of plankton. We usesatellite data to help get thesemeasurements. It’s really cool tocombine technology from space withgenetic analysis of marine organismsto save human lives!”

This Coastal Zone Color Scanner image of the Bay ofBengal in India , shows a plankton bloom associatedwith cholera a outbreak.

Background photo courtsey of: CZCS Project, NASA Goddard SpaceFlight Center.


Location What They Love Name ExampleSea ice cold Psychrophile Polaromonas

vacuolataDeep-sea vent heat Thermophile Pyrolobus

fumariiDeep sea pressure Barophile Colwellia

hadeliensisSulfuric spring acid Acidophile Sulfolobus

acidocaldariusSoda lake alkali Alkaliphile Natronobacterium

gregoryiSaltern salt Halophile Haloferax volcaniiCliffs rocks Lithotroph Thiobacillus

ferrooxidansDesert dryness Xerophile Xeromycees

bisporus

IACTIVITY:ACTIVITY:The ocean contains many environments that

are completely different from our own: tostart with, it’s salty. In many places, it’s way

too cold for our comfort, but organisms fromwhales to algae to microbes call it “home sweethome.” Others find the high pressure at the oceanfloor cozy. But extremophiles don’t just live in thesea. The chart to the right shows some of theplaces they like.

In this activity, you will recreate some of theseextreme conditions and see how they affect theproteins in a “normophile” cell. You will use a cellthat is big enough to see without special equip-ment: a chicken egg. Could this cell survive in anextreme environment?

Materials• 5 raw eggs, cracked open carefully so the yolk

remains intact

• 5 bowls or cups to hold the raw eggs and theliquids below

About 10 ml of the following:

• A 9% solution of salt (9 grams salt to 100ml water);

• A 9% solution of bleach (pH 12)

• Vinegar (acetic acid, pH 4.5)

• Boiling water

Freezer

FocusHow can you simulate the followingextreme conditions: high salinity,alkalinity (high pH), acidity (low pH),extreme cold, and extreme heat?

HypothesesWhat do you think will happen tothe proteins in a raw egg when theyare exposed to those five extremes?Do you think the proteins canprotect themselves from damage?Can they repair the damage oncethey are removed from the extremecondition?

Experiment and Find OutDevelop a way to test yourhypotheses using the materialssuggested. Write up your proce-dure, record your data, anddevelop a theory about thenature of normophileproteins.



Resources

This issue on marine biotechnology allows us todip beneath the surface of our planet’s oceansand discover amazing worlds populated by a

tremendous variety of fish, mammals, and microorgan-isms. We hope you enjoy exploring this world andlearning about marine biotechnology research.

We hope that having a better understanding of the re-search taking place in this and other rapidly developingfields of biotechnology will encourage you to study scienceand mathematics. Perhaps you will select biotechnology asa career and help discover tomorrow’s science.

Sincerely,

Jeff DavidsonExecutive Director, Pennsylvania Biotechnology Association

PBA would like to acknowledge University of MarylandBiotechnology Institute’s Center of Marine Biotechnology fortheir assistance and support in preparing this issue of YourWorld/Our World.

We are able to publish Your World/Our World only because ofthe support of the companies and organizations listed below.Please join us in thanking them for their support:

SponsorsThe Alliance for Science EducationBiotechnology Industry OrganizationCentocor, Inc.Fisher Scientific, Inc.Merck Institute for Science EducationPasteur Mérieux ConnaughtRhône-Poulenc Rorer GencellTosoHaasPECO Energy Company

Supporting OrganizationsUtah State University Biotechnology CenterMassachusetts Biotechnology CouncilMaryland Bioscience Alliance

Dear Students:

SUBSCRIPTION INFO

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Your World/Our World is designed to bring biotechnology tolife by featuring scientific discoveries and applications in aclear and informative way. Issues on different topics inbiotechnology are published each Fall and Spring. If youwould like information on subscribing (individual, teacher, andlibrary sets are available) or on sponsoring distribution toteachers in your area please call the Alliance for ScienceEducation/Pennsylvania Biotechnlogy Association at800.796.5806. Twelve previous issues have been publishedand some back issues are available.

Photo courtesy of Marine Biology Laboratory

Sail The SeasThe 1998 World’s Fair in Lisbon, Portugal is devoted to the ocean. Ifyou can’t make it to the fair, you can take a virtual trip and learnabout the marine world along the way. Pick your travel plan to thispermanent learning and entertainment center:1) Fly by space shuttle and use remote sensing technology to study

whale migration and the ecological system that supports this largestmammal on earth. You can also study the ocean’s weather:www.seawifs.gsfc.nasa/gov/OCEAN_PLANET/HTML/oceanogra-phy/

2) Sail across the ocean on the research vessel Eagle. Use naviga-tional tools and research instruments to study whales. For terrificNational Geographic images, visit: chili.rt66.com/hrbmoore/NGSImages/NGS.html

3) Submerge yourself in the Jason, an underwater exploration vesselthat explores the deepest parts of our oceans. Visit hyperthermalvents, climb mountains and canyons, and see marine shows:www.jasonproject.org

4) For video clips of thermal action, see www.pmel.noaa.gov/vents/geology/video.html

5) Lisbon at last! Once at the permanent virtual World’s Fair, follow astudent guide to the Ocean Supermarket display of all theeveryday products derived from the sea. Visit the world’s largestand most modern aquarium: expo98.pt.pt.default.html

Go Surfin’!• Thermophiles: whyfiles.news.wisc.edu/022critters/hot_bact.html• Extremophiles: www.sciam.com/0497issue/497marrsbox1.html• Deep-sea vents: www-step.uscd.edu~personal/bartram/html.96/

index.html• Marine pharmacology: www-csgc.uscd.edu/communication/MP.html• National Cancer Institute’s Division of Natural Products “Cancer

Web:” www.graylab.ac.uk/cancernet/600733.html• Columbus Center for Marine Biotechnology:

www.columbuscenter.org• Marine Biological Laboratory: www.mbl.edu• Woods Hole Oceanographic Institute: www.whoi.edu• National Ocean Science Bowl: core.cast.msstate.edu/nosb.htmlBeach ReadingPlanet Ocean: Making Sense of Science Series,by Brian BettStart Exploring Oceans: Discover the Wonders of Life Underwater, byD.M. Tyler and J.C. TylerUnderwater Wilderness: Life in America’s National Marine Sanctuar-ies and Reserves, by Charles SeabornYoung Scientists Undersea, by C. Pick

Documents

BIOTECHNOLOGY & YOUhardmanenvsci.weebly.com/uploads/5/2/0/5/5205206/yw-72...Alan Gardner, SmithKline Beecham Anthony Green, Puresyn, Inc. Mary Ann Mihaly Hegedus, Bioprocessing Resource