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2 UNIT 14: T HE HUMAN GENOME PROJECT E I B E Eur opean I ni ti ati ve for Biotechnology Educati on 1 9 9 8

EIB E Co-ord inatorHorst Bayrhuber, Institut fr die Pdagogik der Naturwissenschaften an der Universitt Kiel, Olshausenstrae 62,D-24098 KIEL, Germany. Telephone: + 49 (0) 431 880 3166 (EIBE Secretary: Ute Harms). Facsimile: + 49 (0) 431 880 3132.

EIBE Co n ta c t sAUS TRIA Rainhart Berner, Hhere Bundeslehr- und Versuchsanstalt fr Chemische Industrie Wien, Abt. fr Biochemie,Biotechnologie und Gentechnik, Rosensteingasse 79, A-1170 WIEN.B E L G I U M Vic Damen / Marleen Van Strydonck, R&D Groep VEO, Afdeling Didactiek en Kritiek, Universiteit Antwerpen,Universiteitsplein 1, B-2610 WILRIJK.DENMARK Dorte Hammelev, Biotechnology Education Group, Foreningen af Danske Biologer, Snderengen 20, DK-2860 SBORG. Lisbet Marcussen, Biotechnology Education Group, Foreningen af Danske Biologer, Lindevej 21, DK-5800 NYBORG.

EIRE Catherine Adley / Cecily Leonard, University of Limerick, LIMERICK.

FRANCE Grard Coutouly, LEGTP Jean Rostand, 18 Boulevard de la Victoire, F-67084 STRASBOURG Cedex. Laurence Simonneaux / Jean-Baptiste Puel, Ecole Nationale de Formation Agronomique, Toulouse-Auzeville,Bote Postale 87,F-31326 CASTANET TOLOSAN Cedex.GERMANY Horst Bayrhuber / Eckhard R. Lucius / Regina Rojek / Ute Harms / Angela Kro, Institut fr die Pdagogik derNaturwissenschaften an der Universitt Kiel, Olshausenstrae 62, D-24098 KIEL. Ognian Serafimov, UNESCO-INCS, c/o Jrg-Zrn-Gewerbeschule, Rauensteinstrae 17, D-88662 BERLINGEN. Eberhard Todt, Fachbereich Psychologie, Universitt Gieen, Otto-Behaghel-Strae 10, D-35394 GIEEN.

ITALY

Antonio Bargellesi-Severi / Alessandra Corda Mannino/ Stefania Uccelli , Centro di Biotecnologie Avanzate,Largo Rosanna Benzi 10 , I-16132 GENOVA.LUXEMBOURG John Watson, Ecole Europenne de Luxembourg, Dpartement de Biologie, 23 Boulevard Konrad Adenauer,L-1115 LUXEMBOURG.THE NETHER LANDS David Bennett, Cambridge Biomedical Consultants, Schuytstraat 12, NL-2517 XE DEN HAAG. Fred Brinkman, Hogeschool Holland, Academy for Communication, Postbus 261, NL-1110 AG DIEMEN. Liesbeth van de Grint / Jan Frings, Hogeschool van Utrecht, Educatie Centrum voor Biotechnologie, FEO,Afdeling Exacte Vakken, Biologie, Postbus 14007, NL-3508 SB UTRECHT.S PA I N

Mara Sez Brezmes / Angela Gmez-Nio / Rosa M. Villaman, Facultad de Educacin, Universidad deValladolid, Geologo Hernndez Pacheco 1, ES-47014 VALLADOLID.S WEDEN Margareta Johansson, Freningen Gensyn, PO Box 37, S-26881 SVALV. Elisabeth Strmberg, strabo Gymnasiet, S-45181 UDDEVALLA.

THE UNITED KINGDOM Wilbert Garvin, Northern Ireland Centre for School Biosciences, NIESU, School of Education, The Queens University of Belfast, BELFAST, BT7 1NN. John Grainger / John Schollar / Caroline Shearer, National Centre for Biotechnology Education, The University of Reading,PO Box 228, Whiteknights, READING, RG6 6AJ. Jill Turner, School of Nursing and Midwifery, 1-3 College Park East, The Queens University of Belfast, Belfast, BT7 1LQ. Paul Wymer, Society for General Microbiology, Marlborough House, Basingstoke Road, READING RG7 1AE.

The European Initiat ive for Biot echnology Educat ion (EIBE) seek s to promote skills, enhance understanding and facilitate informed public debate through improved biotechnology education in schools and colleges t hroughout t he European Union (EU).


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E I B E European I ni ti ati ve for Bi otechnology Educati on 1 9 9 8 3 UNIT 14: T HE HUMAN GENOME PROJECT . . . . . . .

14 U N I T

The HumanG e n o m e P ro je c t

World Wide Web

Few areas are developing as rapidly as biotech-nology. So that they can be revised and kept up-to-date then distributed at minimum cost, theEIBE Units are published electronically.

These pages (and the other EIBE Units) areavailable throughout Europe and the rest of theworld on the World Wide Web. They can befound at:

http:/ / www.eibe.reading.ac.uk:8001/

All of the EIBE Units on the World Wide Webare Portable Document Format (PDF) files.

This means that the high-quality illustrations,colour, typefaces and layout of these docu-ments will be maintained, whatever computeryou have (Macintosh - including Power PC,Windows, DOS or Unix platforms).

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The Acrobat Reader 3 programme is availablefree-of-charge. It can be downloaded from:

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With this software, you can view or print theEIBE Units. In addition, you will be able tonavigate around and search the documentswith ease.

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M A T E R I A L S

European I ni ti ati ve for Biotechnology Educati on

Contents

Copyright 4

About this Unit 5

The Human Genome Projec t(HGP)

Introduction 6 The Sanger sequencing method 8 Student Notes 9

Techniques used in the HGPMapping and sequencing the human genome Information for the teacher 11 Worksheet 1 14 Worksheet 2 15 Appendix 16

Social and ethical implications ofthe HGP

L ife insurance: an ethical dilemma? Information for the teacher 17 Student Text 1 19

Patenting DN A sequences - an ethical

question Information for the teacher 20 Student Text 2 21

December 1998


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EIBE cont ributorsUte Harms (Unit Co-ordinator)IPN at The University of Kiel,Germany

Vic Damen The University of Antwerp,Belgium

Wilbert Garvin The Queens University of Belfast,Northern Ireland

Angela Gmez-Nino The University of Valladolid,

SpainMara Sez

The University of Valladolid,Spain

Jill Turner The Queens University of Belfast,Northern Ireland

Design, illustration and typesetting:Caroline Shearer, NCBE, The University of Reading, UK

Copyright This EIBE Unit is copyright. The contribu-tors to this Unit have asserted their moralright to be identified as copyright holdersunder Section 77 of the Copyright, Designsand Patents Act, UK (1988).

Educational use. Electronic or paper copiesof this EIBE Unit, or individual pages fromit may be made for classroom use, providedthat the copies are distributed free-of-charge or at the cost of reproduction, andthe contributors to the unit are credited andidentified as the copyright holders.

Other uses. The Unit may be distributed byindividuals to individuals for non-commercial purposes, but not by means of electronicdistribution lists, mailing (listserv) lists,newsgroups, bulletin board or unauthorisedWorld Wide Web postings, or other bulkdistribution, access or reproduction mecha-nisms that substitute for a susbscription orauthorised individual access, or in anymanner that is not an attempt in good faithto comply with these restrictions.

Commercial use. Should you wish to usethis material in whole or in part for com-mercial purposes, or to republish it in anyform, you should contact:

EIBE Secretariatc/o Institut fr die Pdagogikder NaturwissenschaftenUniversitt KielOlshausenstrae 62D-24098 KielGermany

Telephone: + 49 431 880 3166Facsimile: + 49 431 880 3132E-Mail: [email protected]


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E I B E European I ni ti ati ve for Bi otechnology Educati on 1 9 9 8 5UNIT 14: T HE HUMAN GENOME PROJECT . . . . . . .

About t his Unit

This unit comprises activities, information,texts for discussion, and case studiesdesigned to be used independently or inseries as part of a teaching programme. Thedifferent parts have been devised bypractising teachers and educationalists fromseveral European countries, broughttogether with support and encouragementfrom DGXII of the EuropeanCommission, under the auspices of EIBE,the E uropean Initiative for Biotechnology E ducation.

All the materials have been tested inworkshops involving teachers from manyparts of Europe.

This unit consists of several sections:

The Human Genome Project (HGP) This includes basic information for teachersand students about the Human GenomeProject (HGP), i.e. aims, methods andethical and social implications connected tothe HGP. The purpose of this informationis to offer insights into the complexity of the HGP and stimulate an awareness of thebenefits and problems that may arise fromit in the future.

Techniques used in the HGP This is an activity to enable students tolearn about two basic molecular biologicalmethods that are used in the HGP, i.e. themethods of mapping and of sequencingthe genome, in order to provide an insightinto how such a huge genome as the humangenome can be deciphered.

Social and ethical implications of the HGP Two activities are described involvingethical, social and legal implications of theHGP which are as equally important to theteaching of this topic as the biological and

technological aspects. One of the problemsrelated to the HGP is the how insurancecompanies will use the information which

becomes available from the project.Students are provided with information toguide them in recognising possibleconsequences of the availability of resultsfrom the HGP, a problem that they mayhave to face personally in the future. Theyare also given guidance in finding their ownstandpoint on the topic.

This part of the Unit includes a case studythat deals with the problem of how thepatenting of DNA sequences can behandled. On the basis of the case study,students use an ethical analysis as a modelof the decision-making process. First,guidance is given on ways of reasoning outan ethical problem related to the HGP.

Secondly, support is provided for coming toa personal substantiated judgement aboutone problem connected with the HGP.

Comments on these materials are verywelcome, especially from teachers, at whomthey are principally aimed. Comments andqueries about this Unit should in the firstinstance be sent to:

Dr. Ute HarmsInstitute for Science EducationUniversity of KielOlshausenstrasse 6224118 KielGermany

Telephone: ++49 (0) 431 880 3151Fax: ++49 (0) 431 880 3132e-mail: [email protected]


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Introduction

Th e H u m a n G e n o m e P r o je c t The Human Genome Project (HGP) is aninternational programme aiming to improveunderstanding of the basis of humanheredity. It focuses on the completecharacterisation of the human genome, allthe human genetic material, including theestimated 50,000 to 100,000 genescontained in human DNA. The HGP is oneof several genome projects designed todescribe the genomes of bacteria, yeast,crop plants, farm animals, and organismsused in medical research. One central aim

of all these projects is to promote theunderstanding of the basic biochemicalprocesses of living organisms. It is hopedthat outcomes of the HGP will be to makepossible early detection of human diseases,effective preventative medicine, efficientdrug development, and personalisedtherapies.

Tec hniq ues of the HGP The HGP, which is expected to last for 15years, has two major components: first, thecreation of maps of the 23 pairs of humanchromosomes and secondly, the sequencing

of the DNA making up thesechromosomes.

Geneticists use two types of maps tocharacterise the human genome: geneticlinkage maps and physical maps (see Fig.1).

The maps depict the relative positions of DNA markers; both known genes andDNA sequences with no known codingfunction.

Genetic Linkage MapsAt the lowest resolution genetic linkagemaps depict relative chromosomal locationsof DNA markers and are created byfollowing the pattern in which they arepassed through family pedigrees in relation

to other known markers.Physical MapsPhysical maps describe the characteristicsof the chromosomal DNA molecule andcan be at several levels of resolution. Atthe lowest resolution is the cytogeneticmap, showing the chromosomal bandingvisible in stained chromosomes. Higherlevel physical maps are achieved by dividing

the chromosomal DNA into shorterfragments (which may include the markersof the genetic linkage map) with restrictionenzymes. The fragments are then

T E A C H E R S N O T E S

A B C D

C G A C T A G G G T G G T G C C A C G T A C T A C G

500 kb

F ig u r e 1 . M a p p in g a c hr o m o s o m e

stained chromosome showing banding

restriction fragments showing genetic markers

complete DNA base sequence

genes

PHYSICAL MAPS

GENETIC LINKAGE MAP


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duplicated and characterised. The correctlocation and order of the fragments on thechromosome is then deduced usingoverlapping common sequences as guides.

SequencingUltimately the characterisation involvesdetermining the complete base sequence of the fragments (the highest resolutionphysical map). One of the most frequentlyused sequencing methods is that of Sanger(see page 8 ).

An important technique used to propagateDNA fragments in the mapping andsequencing activities of the HGP is thepolymerase chain reaction (PCR). A detailed

description of this can be found in EIBEUnit 2 DN A -profiling .

Socia l and e th ica l impl ica t ions oft h e H G P

The HGP is planned to be completed bythe year 2005. It is expected to enableprogress in medical and pharmaceuticalresearch, and in medical diagnosis andtreatment to be made on a scale that was

not dared to be hope for some years ago.However, as well as these hoped foroutcomes of the HGP, several objectionshave been raised concerning ethical, socialand legal questions.

A major criticism of the HGP is that thehigh costs of this project cannot be

justified. The whole project will cost at least3 million dollars. Funding such a hugeproject reduces the financial resources leftfor smaller research programmes thatperhaps would be more effective than theHGP. In addition, it is questionable whetherthe expected advances in the treatment of so-called illnesses of civilisation, such ascancer, heart disease, Parkinsons andAlzheimers disease, can a priori legitimisesuch a large expenditure of money at thecost of provision of services in primaryhealth care.

The results of the HGP will increaseknowledge about single gene disorders

without necessarily any immediate possibil-ity of therapeutic treatment. Additionally,the publicity about research connected tothe HGP is possibly raising expectationsamong the people concerned that theproject cannot fulfil. As most diseases arepolygenic and multifactorial, the questionof handling more precise knowledge aboutsusceptibility, without possibilities of treatment, will become a problem.

The amount of information coming out of the HGP is unbelievably huge. I t has beenestimated that the whole DNA basesequence printed in small letters on thinpaper would need 220 000 pages or eightmetres of a shelf space. In parallel with the

advances in biology and methodology thatare necessary for deciphering the humangenome, developments in computing willcontinue to be needed to store, process andanalyse all the data. Furthermore, questionsstill remain about who will own the data,who may use them and how their use willbe supervised, as well as the ethical andlegal aspects whether or not DNAsequences can be patented.

Another ethical problem is the questions of the right of not being willing to know andthe obligation to be informed. This willoccur if, for example, genetic screening of employees or in pregnancy were to becomea legal requirement

Some of the implications referred to aboverequire a legal answer, e.g. data security,commercialisation and patenting. Others,however, have relevance to the ethicalvalues of individuals and society as a whole.

They touch on fundamental ethicalquestions and even the problem of moralpluralism. This unit, therefore, givesstudents an opportunity to become awareof aspects of the HGP that are inherent tothe project by confronting them with casestudies which involve some of these keyquestions. It is also the intention to helpthem to make their own personal, rationaldecisions on at least some of the questionsby using a model of ethical analysis.


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C G A C T A G G G T G G T G C C A C G T A C T A C G C G C A

+ dd A TP

+ dd C TP

+ dd G TP

+ dd T TP

A ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? G CG T

5 3

A ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? G C G T

A ? ? ? ? ? ? ? ? ? ? ? ? ? G C GT

A ? ? ? ? ? ? G C G T

A ? ? ? G C G T

HH

HH

HH

HH

HH

+ d d A TP

? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? C G C A5 3

+-

G C G T+

DNA polymerase +

d A TP + d C TP + d G TP + d T TP+

P PP O C H 2 O

HH

HH

HH

b a s e *

didesoxynucleotide (dd * TP)+

F igu re 2 .

D NA s e q u e n c in g u s in g t h e S a n g e r m e t h o d

The Sanger method involves the synthesis of radioactively labelled DNA strands that are complementary to the single-stranded DNA fragment under investigation.

When a didesoxynucleotide, e.g. ddATP in the red tube, is incorporated into the DNA molecule (in place of dATP) the chainterminates at that point so that fragments of different lengths are formed that have grown until the ddATP stopped the chain at apoint of incorporation of an adenine base.

The complementary DNA is synthesised using:a short radioactively labelled starter (the primer);the enzyme DNA polymerase;four nucleotides;one didesoxynucleotide.

Four parallel reactionmixes are used, eachcontaining one of the four didesoxynucleotides.

Gel electrophoresis is then used to separate the fragments by size.

The radioactive label reveals the positions of the fragments and fromthe size of the fragments in each mix the base sequence of the complementary, and hence the original DNA fragment can be deduced.


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The HumanGenome Project

The eminent British molecular biologistSydney Brenner brought a hearty laughfrom his audience by suggesting that somefuture graduate student might define amouse as ATC, GCC, AAG, GGT, GTA,ATA ..... Every year, however, the idea of defining an organism by the sequence of itsDNA bases seems a little less far fetched(see http:/ / www.gene.com/ ae/ AB/ IE/Future_Of_Genetic_Research.html). Thisis also true for Man because in the middle

of the 1980s a huge project, named theHuman Genome Project (HGP) was begunwith the aim of deciphering the completehuman DNA.

When, about forty years ago, it was provedthat the DNA molecule is responsible forheredity, it brought together two groups of

researchers; some were interested in thedetermination of the loci and the functionof genes, while others wanted to know thestructure of those molecules that includethe information for control of biochemicalprocesses. As a result of this great interest,during the following years more and moreimproved techniques for the isolation,multiplication, manipulation and analysis of DNA fragments were developed. A keyoutcome was the so-called recombinantDNA technology which revolutionisedmedical/ biological research. It madepossible the identification of genes forseveral hereditary diseases. The knowledgegained by this technique showed thatresearch on the decoding of the whole

human genome and the locating of allgenes could be taken a long way further. The achievement of this became thedeclared aim of the HGP.

The two sets of 23 chromosomes in humancells contain about 50 000 to 100 000 genesthat make up probably not more than 5%of the whole DNA. The first aim of theHGP is to determine the location of all

genes on the 23 chromosome pairs, i.e. onthe 44 autosomes and the 2 sexchromosomes. This is followed bydetermination of the base sequence, veryimportant information for the identificationof the particular gene function. Finding thelocalisation of the genes is known asmapping ; the determination of the basesequence is sequencing . The final aim of the HGP is the sequencing of the wholehuman DNA including the non-codingparts.

The information from these investigationswill lead to new knowledge about humandiseases and to new ways of diagnosis andtreatment of disease. In addition, thefindings will give information about theorigin of the various population groups andthe evolution of Man.

The dimensions of the project are difficultto imagine. For example, if you magnify thesize of a human cell to the circumference

F igu re 3 . Th ree human ch romos ome swi th known loc i fo r he red i t a ry d i s eases

S T U D E N T N O T E S

gene coding for Cystic fibrosis

gene coding for Sickle cell anaemia

gene coding for one formof Alzheimers disease

Chromosome pair 7

Chromosome pair 11

Chromosome pair 14


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of the earth, one chromosome would havethe dimension of a country, a gene thedimension of a city and the bases would bethe equivalent of the inhabitants. In thisworld of a cell, researchers working on theHGP are looking for at least 50 000 genes(cities). Ultimately, it is the intention to findout the sequence of a line of three billionbases (inhabitants).

Questions and activities

1. What is the HGP?2. Why is the HGP being carried out?Sit together in groups of three to four. Tryto find and formulate as many ideas aspossible on the following questions andwrite down your ideas.

3. The HGP is expected to cost about 4billion pounds sterling, about a tenthof what it cost to put a man on the

moon. Do you think that this will bemoney well spent?

Ta b le 1 . Ch r ono lo gy o f re s e a r c h on t he hum a n ge nom e

1953 J ames D. Watson and Francis F. Crick find out the double helix structure of the DNA.

1966 The genetic code is deciphered: three base pairs build one triplet and determine one amino acid in a protein.

1973 Herbert Boyer and Stanley Cohen prove that DNA that has been cut and recombined is active in a living cell.

1977 The first human gene is isolated; the gene for insulin.

1985 Renato Dulbeco proposes the sequencing of the whole human genome.

1987 The Italian Human Genome Project (HGP) is started.

1988 The Human Genome Organisation (HUGO) is founded at Cold Spring Harbor (USA)involving more than hundred members in many countries worldwide.

1990 The Human Genome Project is started officially in the USA with funding of 3 billion US dollars and a timespan of 15 years .

The French HGP is started.

1995 The German HGP is started with annual funding of 50 million DM

1996 85% to 90% of all human genes are identified.

4. Can you think of any benefits from theinformation that will become available?

5. How do you think that this knowledgecould best be used for the benefit of allmankind?

6. All of the data is being put on adatabase by HUGO (the HumanGenome Organisation) which was setup in 1989 to co-ordinate the variousactivities in the contributing countries.Who do you think should own the dataand who should be allowed access tothem?

7. Should the information generated bythis project be exploited forcommercial reasons?

8. Would you like to know the details of your own genome? Who else shouldknow about this information? Whoshould not have this information?


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Techniques usedin the HGP

Mapping and s equenc ing

The HGP is possibly the most important,interesting and challenging scientific projectat the present time. We are inundated withinformation about it in the media whichoften stimulates students to ask questions.

Thus the HGP provides manyopportunities for placing the educationalprocess in a relevant context.

When discussing the mapping and

sequencing of the human genome, studentsinvariably ask how is it actually achieved. Itis relatively easy to talk about such mattersin general terms but the principles aredifficult to explain. However, providingstudents with an active learning situationoffers more fruitful approach to learning .Although the practical techniques thatresearchers use are not applicable toschools, a situation has now been reachedwhere equipment is available for students tohave an opportunity to cleave DNA withrestriction enzymes and separate theresulting DNA fragments in a gel tank. Forexample, the National Centre forBiotechnology Education (NCBE) at TheUniversity of Reading has produced such akit containing gel tanks, microsyringes,DNA and restriction enzymes at anaffordable price of around 125.

An alternative, and very cost effective,method is to mimic the practical situationwhich not only demonstrates the principlesinvolved but also provides opportunities forstudents to think and to solve problems.

The s ize of t he problem The human genome has been estimated toconsist of 4 Gb (one gigabase = 10 9 bases).It has, however, been estimated that around

95-98% of the genome is junk. Note thatit is described as junk and not garbage -

garbage we throw away, whereas we keep junk in the hope that someday it might beuseful! Researchers are divided into twocamps - those who think that we shouldconcentrate on mapping and sequencingthe 2-5% that codes for polypeptidesequences (about 100,000 genes), and thosewho think that we should look at thecomplete genome since much of the junkcould be found to have important functionssuch as regulating the genes. Interestingly, ithas been found that those organisms withrapid life cycles, e.g. unicellular microbesand some multicellular organisms such asnematodes, do not possess junk DNA.

They appear to keep their genomesstreamlined so that the process of cell

division is speeded up.Unfortunately, at present there are no easyand inexpensive methods for sequencingDNA. Even if there was a machine thatcould produce a million nucleotide pairs of sequence each day, it would still take about20 years to sequence the entire humangenome - and this is about 100 timesgreater than the present production of

sequences by research centres in the wholeworld. It is likely, therefore, that the mostimportant genes will be sequenced first, andthen, as the technology improves, theremainder of the genome will gradually becompleted. Although a date of 2005 hasbeen set for completion of the HGP, thiscould be an optimistic aim although theincreases in the use of automated methodscould help in attempts to achieve this target.

B ase s equenc ing - t he ac t i v i t yIn this paper exercise, DNA is broken up orcleaved using a variety of restrictionenzymes (restriction endonucleases). Howcan the sequence of bases then beassembled in the correct order? Theresulting short strands of cleaved DNA areexamined for any overlapping sequencesand these are then matched.

This exercise mimics the followingrestriction enzymes which cut DNA at the



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for overlapping sequences. Other newtechniques are continually being developedto improve and speed up the process of gene sequencing, including the use of fluorescent-labelled gene probes and thescanning tunnelling electron microscope.

F ur the r r ea d ingCiba Foundation (1990) H uman Genetic Information: Science, L aw and E thics , JohnWiley & Sons.Evans, E. (1993) The H uman Genome Project ,Biological Sciences Review, 5 (5), 2-5.

Jones, S. (1994) The L anguage of the Genes ,Flamingo.McKusick, V.A. (1971) The mapping of human chromosomes , Scientific American, 224 , 104-

113.Science and Technology in Society (SATIS)14-16 (1991) Unit 1202 M apping the H uman Genome . Association for Science Education.Suzuki, D and Knudtson, P. (1989) Genethics,the Ethics of Engineering L ife . Unwin Hyman,London.Wills, C. (1992) Exons, E ntrons and Talking Genes - the science behind the H uman Genome Project , Oxford University Press.


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W O R K

S H E E T 1

DNA Sequencing 1

1. Examine one of the two strands of single-stranded DNA that you have beengiven. Starting from the left, identify the restriction sites at which the restriction

enzyme would cut. Use the appropriate restriction enzyme for the colouredstrand according to the colour code:

Enzyme Rest ric t ion Sit e Colour

Hae III GGCC pink

Eco R I GAATTC green

Eco R II CCTGG yellow

Hpa II CCGG blue

Cut the strand of DNA carefully and as neatly as possible at the restrictionsites with scissors.

You should now have a number of segments of DNA of different lengths.

2. Repeat procedure 1 with the second strand of DNA.

3. When you have completed this, mix all the segments and go to Worksheet 2.

Hae III

Eco R I

Eco R II

Hpa II


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W O R K

S H E E T 2

DNA Sequencing 2

4. Your next task is to reconstruct the original sequence (order) of the bases (A, T,G and C). Look for overlapping sequences; these will help you. Remember that

you are not making base-pairs. The bases of each differently coloured strandmust match as follows:

G G A A T T C C T G G C C T G G A A T T

By moving the pieces around and trying various combinations you should beable to reconstruct the original sequence. Once you have finished, check thesequence with the teacher.

Methods have now been developed that use computers to search foroverlapping sequences. In this way the complete sequence of bases of all thegenes in the human genome will be worked out.


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C C T

G G C C G G C C T G G

C C T G G A A T T C C G G C C T G G A A T T C

C G G A A T T C C G G A T T C C T G G

C C T




C C T




C C T




C C T




C C T




C C T




C C T




C C T




C C T




C C T




C C T




C C T




C C T




C C T




C C T




C C T




C C T




C C T




C C T




C C T




C C T




C C T




C C T




A P P E N D I X


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Life insurance - anethical dilemma?

Aims

The aims of this activity are to:develop students skills for resolvingmoral problems;demonstrate that some problems donot have clear, objective solutions but,that in an ethical decision makingprocess, feelings and emotions oftenpredominate;show that scientific discoveries haveconsequences for the whole of society.

Organisa t ionA possible way to proceed with this activitywould be, after a balanced introduction of the concept and scientific content of thehuman genome project , to use the activitytext ( page 17 ) as an introduction to somemoral problems related to genetic disordersand life insurance.

The two cases and some related issuescould be discussed, further informationobtained if required (e.g. from insurancecompanies), and possible solutions consid-ered, initially working in small groups.Conclusions could then be presented to thewhole group in a plenary session.

B ackground i n fo rmat ion andq u e s t io n s f o r d is c u s s i o nInsurance

An insurance company calculates premiumsby considering the actual situation andrelating it to the risk that has to be insured.

The premiums for group insurance andprivate insurance are different. Groupinsurance premiums are calculated on thebasis of an average population with apredictable risk factor where the insurer hasan obligation to insure every member of that particular population. There are many

more options in private life insurance, whenevery potential policyholder can choose

when to be insured, how much premium topay and the length of the period of insurance. The insurer also has choices and,before accepting a policy holder, maydemand some medical guarantees. With thisprocedure, insurers are able to develophomogeneous risk groups within whicheveryone pays the same amount for thesame risk.

Genetic diagnosisWith the present techniques of geneticdiagnosis, an individual with a possibility of Huntingtons disease is examined for thatdisease only, and not for cystic fibrosis orother known genes. However, withknowledge gained from the HGP and

automated DNA screening techniques itmay be possible in the future to provide acomplete genome checkup.

Is this the purpose of the H GP? What about the right of privacy? Could this right of privacy be used to prevent an insurance company from rejecting an application for life cover? Why would anyone want to look into a crystal ball

when there is a substantial risk of learning some distressing news about expectations for the future?

One of the concerns about geneticdiagnosis is its ability to identify a multitudeof possible inherited diseases. Suchknowledge can, however, be of great valuein helping people take important decisions.For example, a couple with a history of aninherited problem might want moreinformation before deciding to havechildren, a sportsperson with a familyhistory of inherited muscular problemsmight want further information beforeundergoing rigorous training. It might bevaluable to screen individuals for aninherited condition which could lead,without surveillance, to a serious disease.Uncertainties about risks are often harderto bear than the certain knowledge of beinga gene carrier.

At present genetic screening is performed


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Rapidly increasing knowledge about thehuman genome together with newtesting techniques will make it easier to

diagnose certain genetic conditions.What if the prognosis is early death or alifelong mental handicap? Does testingin this case makes sense? Consider thefollowing examples.

Exam ple 1 You have applied for life insurance. Youcompleted the forms sent to you by theinsurance company asking questions aboutyour medical history and any diseases inyour family, and you have passed a medicalexamination.

Last week you received a letter from theinsurance company stating that personal lifeinsurance was only possible if a DNA testconfirmed that no hereditary disease waslikely to reduce your life expectancy.

This came as a complete surprise and youconsulted a geneticist at the local universitybefore deciding whether to have the test.On hearing that your son had cataract, thegeneticist wanted to know more about therest of the family and drew up a family tree.

This showed three family memberssuffering from cataract. You then told himabout your sons motor problems and thathe had been given a programme of specialphysical exercises. According to the

geneticist, the combination of cataract andmotor problems could indicate myotonicdystrophy, or Steinerts disease. This ischaracterised by progressive muscularweakness and spasms.

It is possible for this illness to be present ina family without it being recognised as such.If this diagnosis is correct, there are alsolikely to be complications such asdisturbances of heart rhythm, glucoseintolerance, and accompanying educationaland career problems. It is also likely that

the problem will become more and moreserious in future generations, aphenomenon known as anticipation.

The geneticist points out that if the DNAtest shows the presence of this autosomaldominant condition, you are facing a hugedilemma! Myotonic dystrophy is on the listof diseases that would exclude you from lifeinsurance. A confirmed diagnosis wouldmean that you and some members of yourfamily will no longer be eligible for lifeinsurance!

Your d i lemmas:What if you refuse the DNA-test?

What about the possibility of passing onthe disease to future generations?

What about treatments?

What if an insurance company puts pressure on other members of your family to have a DNA-test for carrier status (and therefore to no longer be eligible for life insurance). Is this acceptable?

What about freedom of choice?

Exam ple 2Many firms and organisations offer theirpersonnel the opportunity of taking out lifeinsurance. Frequently these schemes do notrequire detailed information about the healthof the family, or even about the personinsured! The insurance company acceptseveryone, without medical screening, oncondition that a certain proportion of employees take up the insurance.

Thus, although anyone with myotonicdystrophy would be excluded from lifeinsurance by personal application, it couldbe available through the collectiveinsurance scheme of an employer.

Is collectivity, the basic idea of insurance,

the way out of the impasse as presented in case 1?

S T U D E N T T E X T 1

Life insurance - an ethical dilemma


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Patenting DNAsequences - anethical quest ion

Aims The student material presents a case studythat forms the basis for an ethical analysis.

The aim of this analysis is that the studentswill:

become aware of the need, indiscussions, to differentiate betweendescriptive and normative statements(for further information see EIBE Unit

10: Transgenic Plants: Economy,Environment and E thics );understand the ethical values on whichtheir arguments and decision makingare based.

B ackground i n fo rmat ion The model of ethical analysis describedhere follows Bayrhuber (1994) and Hoessle(Dissertation at the IPN / Kiel, inpreparation). It helps outline the differentoptions when tackling a moral problem, sothat an assessment can be made of thearguments and their ethical basis (i.e.whether referring to the dignity of mankindor the wellbeing of mankind - fundamentaltypes of ethical argument).

The ethical analysis consists of several steps.

1. Understand the situation.

Students formulate a question to be decidedupon, e.g.: Should the patenting of DN Asequences be legalised or not?.

2. Enumerate the options for action.Students outline possible options for action.In the example above, the options wouldbe:(i) DN A sequences may not be patented; (ii) only DN A sequences with known functions

may be patented; (iii) all DN A sequences may be patented.

3. Relate the different options topossible ethical concerns whichcould arise as a consequence of theactions.

Ethical concerns in the example mightcover e.g. health, the right of self-determi-nation, economic profit.

5. Make a meaningful decision.Referring to the values established in step 3,the students make their decision for one of the possible action options named in step 2.

6. Assign the reason(s) for ones owndecision to the fundamental typesof ethical argument.

See above.

7. Describe the consequences of thedecision.

Students consider the consequences of their decision for the individual and forsociety.

Organisa t ionPreparatory homework As an introductory activity the students

should collect information about patents;using various sources such as the library,newspaper articles, parents.

Session 1At the beginning of the next lesson, gatherthe material collected by the class. Then, byclassroom discussion, decide on suitablecategories into which the material can bearranged, e.g. definitions, examples, problemsconnected with patenting. With the studentsworking in groups of about four, allocate thematerial to appropriate categories. Discuss thefindings in a plenary session of the wholeclass. Assemble and display a summary of thecharacteristics of a patent.

Session 2 The case study (see Student Text 2 ).



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S T U D E N T T E X T 2

Patenting DNA sequences - an ethical question

Th e C a s e S t u d yRead the case study on the right twice.

As a molecular biologist, obviously Ric H. didnot see any objections to his idea of patentinghuman DNA sequences. Do you?

By following the questions below, try to cometo your own reasoned opinion about the case.

Questions

1. What is the ethical problem to beconsidered?

2. What are the possible decisions thatcould be made?

3. In your opinion, what moral issues aretouched on by the various possibilities?

4. Considering the moral concerns, makeyour own individual decision fromthose outlined in question 2.

5. Under which of the following twocategories of fundamental ethicalprinciples would you put the values thatyou found to be most important inarriving at your decision:a) the dignity of mankind;b) the wellbeing of mankind?

6. Describe the consequences of yourdecision for yourself and for society.

Rick H. is one of the many researchers working onthe Human Genome Project, the largest interna-tional research programme ever undertaken. He isan excellent molecular biologist and even thoughhe is still a young man, 35 years old, he is alreadyhead of an institute which specialises in genomesequencing. In addition to the human genomeproject, some of his research groups are busysequencing genomes of different organisms suchas bacteria, crop plants and animals that are of in-terest for pharmaceutical and medical research.

They all have to work very hard. However, in order

to be a researcher you have to be idealistic becausethere is no clear relationship between the amountof work you do and the money you earn.One day Rick read in a scientific journal thatparticular sequences of a mouse genome had beenpatented in the USA. This information made himthink. Patenting a sequence of DNA would meanthat for many years the relevant researchers, or theinstitution where the sequencing was done, wouldown the rights of these sequences. That meant that

if these sequences were of value for the productionof therapeutic agents or for making the diagnosisof a particular disease possible, the patent ownerswould be the first to use the informationcommercially and without competition.Rick sat at his desk late into the night going throughall the sequences they had found during the previousyear. For some of them they already knew thefunction or the particular protein coded for. But allof these genes were already used in various ways in

the pharmaceutical or medical industry. Suddenlyhe had an idea: Why not try to patent the humanDNA sequences they had found, even though theirfunctions were still unknown?

The next day Rick wrote a patent application for ahuman DNA sequence that they had discoveredtwo weeks ago. If it is accepted, the institute mightearn a lot of money if, in the future, the sequenceproved to be of medical importance. When he hadposted the letter he was very proud of his idea. Hecould not wait for the answer to his patentapplication.

genoma project

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