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Human GenomeHuman Genome makesmind-boggling readingGenetic researchers are lookingforward to medical miracles — andbackward into evolutionary historyBy Steve Sternberg

www.usatodaycollege.com

SSuummmmaarryy:: Genetic research promises to yield huge benefits to society whilebecoming a multimillion-dollar industry. The three USA TODAY articles in this

case study explore the challenging questions related to recent discoveries in thebiotech field. If technology redefine the moral landscape, how will it affect

members of the business, political, medical, legal and scientific communities.

DNA-rights defenders: Get off my geneticpropertyMoney creates conflict of researchvs. privacyBy Elizabeth Neus

Thinkers: ‘Genes cannot explain’‘No evidence of 30,000 genesevolving over. . .tens of millions ofyears can tell the whole story.’By Greg Barrett

Genetically altered food:Women more skeptical

Would eatsuch food

USA TODAY Snapshots®

By Lori Joseph, and Sam Ward, USA TODAY

Source: www.pulse.org

Would giveit to theirchildren

Willing topay more fornon-altered

food

Women

50%

71%

37%

59%47%

35%

Men

Human genome makesmind-boggling readingGenetic researchers are looking forward to medicalmiracles — and backward into evolutionary history

Cover story

By Steve SternbergUSA TODAY

The first close reading of the “TheBook of Life” — the 3 billion letters thatmake up the human genetic code —reveals that it’s packed with moremysteries and surprises than a pulpthriller.

Perhaps the biggest surprise sincethe code was deciphered in June isthat it takes just 30,000 to 40,000genes to make, maintain and repair ahuman. That’s far fewer than the140,000 genes that some hadpredicted and not many more than aworm or a common weed.

“If you’re judging the complexity ofan organism by the number of genes ithas, we’ve just taken a big hit in thepride department,” says the NationalGenome Research Institute’s director,Francis Collins, who also heads the U.S.arm of the international HumanGenome Project (HGP).

Twin analyses of the genome werereleased today by two leading journals,Nature and Science. Both issues also arepacked with reports looking at what the

genome tells us about ourselves andhow we differ from other organisms onEarth.

And the genome is the perfect placeto look. If ancient Greeks talked of the“Great Chain of Being,” the genome isit, and in a form that the ancientscould hardly have imagined — aspiraling chain of chemicals runningthrough every living being. In humans,the chain is vast, “25 times larger thanany previously studied genome andeight times larger than the sum of allsuch genomes,” Collins reports.

Among the findings: uMen, whose sperm cells divide

almost endlessly to boostopportunities for fertilization, aretwice as likely as women to generateabrupt genetic mutations. Thesealtered sequences may mingle withthose of the mother’s genes afterfertilization, shuffling wild cards intotheir child’s genetic inheritance. Someerrors may make no difference to thedeveloping fetus, some might bebeneficial, and some might be harmful.What this means to human

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HS01-01

Case Study Expert: Amy Bordeaux, Ph.D.

AS SEEN IN USA TODAY LIFE SECTION, MONDAY, FEBRUARY 12, 2001

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USA TODAY photo illustration: source/PhotoDisc

development is poorly understood. uProteins, the most complex large molecules in nature, are

much more complicated in humans than in animals or plants. uHundreds of human genes appear to have come from

bacteria millions of years ago. Whether the bacteria infectedhumans or they were carried by a virus is still unknown. uEvery human’s genome carries the residues of evolution,

a history stretching back millions of years. The journals discuss these things and many more. Nature

begins with a 68-page report by the genome project, apublicly funded consortium of 20 groups in the USA, UnitedKingdom, Japan, France, Germany and China. Science offers a48-page analysis by J. Craig Venter, CEO of Celera Genomics inRockville, Md., and an equally impressive who’s who ofcollaborators worldwide. Celera is the private company thatspurred the public-private race to solve the genome to itsphoto finish in June. Both groups have produced detailedsequences covering over 90% of the genome. And bothversions agree on the rough number of genes in the genome,the genome’s organization and other key features.

Multi-tasking genes

Probably the most intriguing question to emerge fromthese analyses is this: How do relatively few genes build andmaintain an organism as complex as a human, with 90,000to 300,000 proteins and 100 trillion highly specialized cells?

Venter, whose firm challenged the publicly fundedinternational sequencing project by exploiting a clever,automated technique called “whole genome shotgunsequencing,” says the answer promises to topple a hallowedprinciple of the gene world: “one gene (makes) one protein.”

The new analyses indicate that each gene makes onaverage two proteins. Somehow — the how is still beingexplored — the cell’s machinery can order up the protein itneeds at any given instant, researchers say.

When that occurs, enzymes within the cell swing intoaction. They splice together the genetic sequences thatmake the needed protein, even when the sequences are inpieces, spread out along the chromosome.

This means that the human genome is anything but a staticalphabet. It’s a living text that continually edits and rewritesitself, spelling out biological messages necessary for survival.

“It’s a manuscript in flux,” says Eric Lander of theWhitehead Institute Center for Genomic Research in

Cambridge, Mass., a lead researcher in the HGP. “It’s a never-ending, constantly changing story.”

The substance of the manuscript is more astonishing yet,says Venter. “It is a guidebook to the formation of our species.”

The genome also will serve as a guide for researchers whoare trying to develop new ways of treating cancer and otherailments that have plagued humans. Knowing the identityand location of genes, for instance, enables researchers tostudy their patterns of expression — when they turn on andoff. These clues have already yielded useful information.

One report in Science, for instance, compares geneexpression in normal vs. cancerous tissue. Researchers foundseveral genes that were either “silenced” or over-active inbreast and colon cancer. If doctors can figure out what triggersthese abnormal genetic patterns, researchers say, they may bethat much closer to learning how to block them.

Putting the genome in order

Sequencing the genome involved placing in their preciseorder the seemingly endless strings of nucleic acids thatmake up therungs of the twisted, 6-foot ladder of DNAinside every living cell. The nucleic acids are adenine,thymine, cytosine and guanine. They are represented in thegenome sequence by the letters A, T, C and G.

Over half of the genome is rich in segments called repeats,bits of sequence that appear over and over again, which offera remarkable window into evolutionary history.

“We can look at your DNA or mine,” says Kathy Hudson,assistant director of the National Genome Research Institute,“and see a history going back 800 million years.”

In the genome, says Douglas Wallace, director of molecularmedicine at Emory University in Atlanta, evolution is plain tosee.

Wallace says two lines of evolution converged in humans.One is a set of genes from the first bacteria capable of living inan oxygen-rich atmosphere, he says. The second set comesfrom the single-celled organisms that gobbled up the bacteriaand co-opted their ability to turn oxygen into energy.

Genes from those bacteria still reside in the human genome,the new analysis shows. Says Wallace: “We have the fusion oftwo different lines of evolution into the same genome.”

When researchers speak of the genome, they’re reallytalking about the sum of genetic sequences that make upthe 23 pairs of chromosomes in each human cell, half of each

Book of life: A detail from a diagram of Chromosome 19 shows the complexity of the human genome.

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pair donated by a parent. But the new research indicatesthat this genetic information isn’t evenly divided on thechromosomes. Lander describes the genome as a“remarkably uneven landscape.”

“Some chromosomes are chockablock with genes, (and)others are virtually devoid of genes,” Lander says. “Theweirdest chromosome in the genome is (number) 19. It’schockablock full of genes and other functional elements, farbeyond what you’d expect, given its measly size. It’s a mightylittle chromosome there. Given its size, it has grandaspirations.”

In contrast, he says, “chromosomes 4 and 8 barely pulltheir weight.”

What genes lurk on chromosome 19? Among others: theApo-E gene, linked to Alzheimer’s disease; the LDL receptorgene, linked to bad cholesterol and heart disease; and theEpO gene, needed to form oxygen-carrying red blood cells.There’s even a gene that has been linked to a sometimesfatal, inherited reaction to anesthesia.

No one fully understands the laws that govern genomefunction or how to manipulate the genes to treat humandisease. But genomics and biotech firms, often partneredwith major pharmaceutical firms, are determined to changethat.

A biotech boom

Such research promises to yield huge benefits to patientsof the future — and possibly Nobel prizes to scientists whodevelopnew treatments or even cures. They’ll have plentyto work with.

Researchers have already identified 1,100 genes with atleast one mutation that has been linked to disease. Biotechfirms are uniquely positioned to plunge into such research.

A biotech industry analysis, released late last month byLehman Brothers, asserts that the genomics revolutionwill double biotech revenues to $4 billion annually by2005. The best investments, it says, will be in newlydeveloping technologies.

One of those is the new multimillion-dollar industry thathas sprung up to catalogue what some call the human“proteome,” the complete roster of proteins in the humanbody.

Proteins by the tens of thousands serve as workhorses inevery cell, performing functions necessary for life.

Not surprisingly, plenty of scientists and businessmenwant to get in on the action, despite market ambivalenceabout many other high-tech enterprises.

“You only have to whisper the word proteomics,” saysJosh LaBaer of Harvard University’s Institute forProteomics, “and venture capitalists come knocking at yourdoor.”

Other firms have begun collecting genetic informationfrom human volunteers — twins, if possible — so thatresearchers can study how genes and proteins function inboth healthy people and those with deadly diseases. Thisholds great promise.

“What will come out of this is a complete redefinition ofhuman biology,” says Paul Kelly, CEO of Gemini Genetics inCambridge, England.

Kelly’s firm has forged an agreement with Celera to helpthe genomics firm look for common disease genes, such asthose for osteoporosis and diabetes. Where? In Gemini’spopulations of twins and other research cohorts in Canada,the United Kingdom, New Zealand and Australia.

Celera also has begun moving into proteomics. Celera’ssister company, Applied Biosystems (both are divisions ofApplera Corp.) has matched its breakthrough gene-sequencing device with one that can speedily sequenceproteins.

“Celera is making the biggest play in proteomics ofanybody,” says Venter. “We have $1.1 billion in cash in thebank, and we’re building a facility where we can sequencea million proteins a day.

“That’s driving our program for the discovery of newdiagnostics and therapeutics — particularly in cancer.We’re betting that we can actually do something aboutcancer.”

“We are made of and by protein,” says Harvard’s LaBaer,whose institute plans to obtain physical copies of everyhuman gene and to use those genes to create the hundredsof thousands of proteins.

“Virtually every pharmaceutical today, from aspirin tochemotherapy, works by affecting protein function,” LaBaersays. “This is where the future of biology, and medicine,resides.”

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By Elizabeth NeusGannett News Service

WASHINGTON — Who owns your DNA? The answer might not be you. In an era when the map of the human genome

can be accessed by any professor with an Internetconnection, the question becomes more crucialevery day. Courts and lawyers and legislatureswrestle with it; people who joined medical studieswonder just what their participation means.

Courts have ruled that people who donate actualtissue — pieces of organs, tumors or blood, forexample — have no right to financial compensationif a drug or treatment is developed from researchdone on that tissue.

But DNA, which contains thegenetic blueprint from whichyou were built, seems morepersonal, something whosefate you and you alone shouldhave the right to control.

Oregon is the site of themost recent battle over therights to DNA. The state’s 1995genetic privacy law, one of thefirst in the nation, gives aperson property rights to his orher own DNA. A proposed changeto the law last year would have takenthose rights away. An advisory committee isexpected to offer recommendations to the

Money createsconflict of researchvs. privacy

DNA-rights defenders:Get off my genetic property

AS SEEN IN USA TODAY LIFE SECTION, MONDAY, SEPTEMBER 25, 2000

Health and Science

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governor next month on how to proceed. “There are many competing agendas here,” says Gregory

Fowler, executive director of Geneforum.org, anorganization founded to educate people about gene-related issues. He also is a member of Oregon’s advisorycommittee.

Experts have tried to sort out those agendas for years.This year the federal government strengthened itsregulations protecting human research subjects, hoping tomake more explicit the process by which patients are toldwhat a study will entail.

The National Bioethics Advisory Commission report onwhich some of those recommendations were based notedthe difficulty in protecting subjects no longer physicallyinvolved in a study.

“Researchers are often unclear whether research onhuman tissue makes thepeople from whom it came‘human subjects,’ ” thecommission wrote PresidentClinton.

In some cases, those whodonated the original tissue orDNA are dead, leaving wideopen the question ofwhether new research canbe done with that material —and who has rights to it.

For example, 4,000 of the10,000 people who havetaken part in the 52-year-oldFramingham Heart Studyhave died, and coordinatorsof that study don’t knowwho can give consent to usethe information from the dead volunteers if the studybecomes a commercial venture, as planned. They aretrying to work that out.

“We certainly feel we’re blazing a trail here,” says SusanParis, vice president for university relations at BostonUniversity, which runs the Framingham study.

The usual concerns also come into play when the issue isgenetics. Researchers make every effort to disconnect theDNA samples from the identities of their donors, butexperts still worry.

“No genetic sample can be totally anonymous,” says LoriAndrews of the Institute for Science, Law and Technologyat the Illinois Institute of Technology. “We use DNA inforensics to identify people. I could always figure out whoit is.”

Complicating the issue further is money — lots of it. Biotech and genomics companies have been hot in recent

years in the stock market, and even academic researchers,once seen as above the financial fray, often have start-upcompanies.

The federal government is balking at Framingham’s plansto go commercial; Washington underwrites the famousstudy, which provided the base line for nearly everything

we know about heart disease. Some of the 6,000 livingparticipants are nervous about how their data — whichincludes health histories, blood, tissue samples and DNA —will be used.

“A lot of time and commitment and love have beenpoured into this (by the volunteers), and they’reconcerned that the data isn’t exploited,” Paris says. “But wehave to get over the fact that companies may make money(from the data). How do you do (research) withoutmoney?”

John Kilyk Jr., managing partner with a Chicago law firmspecializing in intellectual property, says that those whobelieve volunteers should get a cut of any proceeds fail tounderstand how much money goes into the researchupfront, compared with what’s earned at the other end.

“There is a lot of money at stake, or at least there’sperceived to be a lot moremoney at stake,” he says. “Butthere’s no guarantee that(researchers are) going to findsomething … What (laypeople)don’t appreciate is the time andmoney involved in getting tothat point, and the number ofwinners and losers.”

Andrews rejects thatargument.

“It’s an unnecessary windfall,”she says. “They’re beingrewarded disproportionately towhat they do. It’s a trick on thepublic. It’s like patenting thealphabet and charging peopleevery time they speak.”

Some companies have founda way to compensate those who volunteer DNA withoutgoing into dollars and cents. A company called DNASciences, which wants to find gene-based tests andtreatments for common illnesses, is building a largedatabase of DNA from scratch by asking volunteers todonate. If a relevant test or treatment is found, anyvolunteer who participated in that study will be offered thetest or treatment free, says chief business officer StevenLehrer. “The whole concept of paying people for (takingpart in) research is very negative,” he says. “It looks like youcoerced them.”

With the trend toward the creation and use of extremelylarge databases such as Framingham and DNA Sciences’Gene Trust, “the property value of any individual genomegets smaller,” says Gillian Woollett, associate vice presidentfor biologics and biotechnology at the PharmaceuticalResearch and Manufacturers of America, a drug industrytrade group.

Besides, she says, what portion of your DNA is yours?The large part of the genome we share with chimpanzees?The part you share with an identical twin?

“Do you own what is unique to you,” she asks, “even ifyou don’t know what’s unique to you?”

Click here uwww.geneforum.org — Geneforum

uwww.framingham.com/heart —Framingham Heart Study

uwww.bioethics.gov — NationalBioethics Advisory Commission. Click on“Reports” to find “Research InvolvingHuman Biological Materials: EthicalIssues and Policy.”

uwww.dna.com — Gene Trust

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By Greg BarrettGannett News Service

The philosopher, the theologian, the biologist and theauthor of spirituality are in basic agreement on this:Revelations released today about the human genome areabout as significant to our understanding of metaphysics aswalking on the moon is to our understanding of theuniverse. A boundary we still cannot fathom.

That is to say, this evolving map of our genes is not likelyto sway matters of the spirit. Never mind the project’sfindings that seem to support Darwinism and free will overcreationism and determinism.

No evidence of 30,000 genes evolving over the course oftens of millions of years can tell the whole story. Sciencecan claim to connect the dots of biology, not sketch thesoul.

Philosopher: “If there were an omnipotent, omniscientand perfectly benevolent god, then I think his or herpurposes are actually incomprehensible,” says ColumbiaUniversity professor Philip Kitcher. “The idea that 30,000genes can explain or not explain anything is kind ofabsurd.”

Theologian: “Genes cannot explain the entire humanphenomenon,” says William May of Washington’s John PaulII Institute. “Is thinking a function of genes? I think not.”

Biologist: “I don’t need to provide for you how many

ounces a soul weighs or how many base pairs it is coded byin the DNA . . . to know that hope is worthwhile and hopeis real,” says scientist Robert Pollack, director of Columbia’sCenter for the Study of Science and Religion. “It is thereality of hope that matters, not the physicality of thesoul.”

Author: “It is not possible to step on God’s toes,” saysNeale Donald Walsch, whose four Conversations With Godbooks have been best sellers. “I think God chuckles at ourastonishment at these rather primitive revelations, verymuch as we smile at a child’s f irst master y ofmultiplication tables.”

Proof of whether mankind was slow in the making orwas created in an instant is not likely to dissuade belief oneway or the other. Either version can be supported by theOld Testament, embraced as sacred text by Christianity,Judaism and Islam. And there are perhaps as manyinterpretations of religious doctrine as there are mutationsof a cell. Both are uncountable. Similarly, there will be anynumber of ways believers and non-believers will read thediscoveries of the human genome.

“The more we learn and the more we know,” Pollacksays, “the more we are aware of the boundaries set uponus by the two facts of our lives: our free will on the onehand, our mortality on the other.”

Two themes constant in religion and science.

Thinkers: ‘Genes cannot explain’AS SEEN IN USA TODAY LIFE SECTION, MONDAY, FEBRUARY 12, 2001

Behind the Story: A Reporter’s NotebookEver since the world discovered Gregor Mendel's research into plant hybridization (first pub-lished in 1865 but apparently overlooked until 1900) scientists have been fascinated with thebiological mechanisms that underlie inheritance. But the world would have to wait untilFebruary 12, 2001 for scientists at Celera Genomics and the Human Genome project to decodethe human genome and begin their exploration of how humans function on a genetic level.Needless to say, anticipation of their findings was intense. For two weeks before the announce-ment, I privately interviewed the leaders of that research effort, gathering the information Iwould need to explain their incredibly complex research to our readers. I felt priviledged to begranted advance access — and broke out in goose bumps when Frances Collins, of the HumanGenome Research Project, showed me the first complete map of the human genetic inheri-tance. I faced two challenges in describing this work: finding analogies that would allow me to

explain in simple terms one of the most complex systems in biology and predicting where this work would lead.The overwhelmingly positive response from readers suggested the effort wasn't wasted.

Steve Sternberg has covered science and medicine for two decades for The Miami Herald, The Atlanta-JournalConstitution and now for USA TODAY. He has won many national awards, including a prestigious John S. KnightFellowship for Professional Journalists at Stanford University, where he studied genetics in the laboratory ofDavid Botstein. Last year, he was awarded a master's degree in science writing from Johns Hopkins University.

Steve Sternberg, Medical reporter, Life

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For discussion

1. Review the USA TODAY Snapshot. Why do you think women aremore skeptical than men about genetically altered food?

2. The human genome tells us about ourselves and how we differfrom other organisms on Earth. It has been found that it takes just30,000 to 40,000 genes to make, maintain and repair a human,which is not many more genes than a worm or common weed.What does this mean? How much difference is there then betweenhumankind genetically, and what implications could this have forunderstanding racial differences on a scientific level?

3. No one fully understands the laws that govern genome functionor how to manipulate genes to treat human disease. For example,understanding chromosome #19 may help us learn how to treatAlzheimer’s disease, bad cholesterol and heart disease. Why mightstudy and research involving twins be a good way to learn andunderstand genes, particularly for preventing diseases like Alzheimer’s?

4. " We are aware of the boundaries set upon us by two factsgoverning our lives: our free will and our morality." Do you agreewith this statement? Why or why not? Consider where this newwork in human genome could lead us, which could be a newredefinition of human biology. Is it right for technology to redefineour moral landscape or for our morals to guide our usage oftechnology? Which comes first? Explain your viewpoint.

Issues about individual donor’srights, once they have donatedtheir DNA to research, haveemerged recently becausebiotech firms stand to makebillions in genome research. Inaddition, experts say, "no geneticsample can be totallyanonymous." Who should ownthe DNA rights, the individualdonor or the research firm?Should the individual surrenderall rights once they donate theirDNA? Should the individual reapany of the benefits if the firmmakes millions, especially sincethere is no guarantee that moneywill be made from researchinitially? Why or why not?Should the federal governmentbe involved in this issue?

Future implications

Amy Bordeaux has over twenty-five years of experience as a science educator in public and private schools,a creator and manager of national, innovative science programs for students, and as an instructional leaderfor preservice and inservice teachers at local, state, and national levels. She received her B.S. in ScienceEducation from the University of Virginia in Charlottesville, Virginia. She received her M.A. in Curriculumand Instruction from Virginia Tech and her Ph.D. in Education from George Mason University in 2002.

Amy has been a consultant for the Challenger Center for Space Science Education in Alexandria, Virginia.She worked at the Challenger Center for Space Science Education as Vice President of Education, managing curriculum andinstructional programs, overseeing formative and summative evaluation, training national faculty, and instigating space science as areform strategy.

Amy has served as a national education consultant for NASA, Research for Better Schools, Educational Technology Think Tank, USATODAY, Total Learning Research Institute, and D.C. Public Schools. She assisted the Deputy Superintendent for D.C. Public Schools asprogram manager for the NSF Urban Systemic Initiative from 1995 to 1997. Amy is the author of several articles on curriculum andtechnology education.

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