Lab Notes Stem Cells

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LabNotes 3 JANUARY 2003 new biology and society Every human being is made of a thousand million, million cells. Most of these cells are highly specialized. For instance, there are nerve cells, blood cells and muscle cells, all of which perform specific tasks. But where did these specialized cells come from? The precursors of all the different kinds of cells an individual has are called stem cells. LabNotes After a few cell divisions, many cells lose their ability to divide as they make up the tissues and organs of the body, though some continue to be the source of new cells for the remainder of our lives.The reason is straightforward: some cells, such as those found in the brain, are created early on in development and are set for life. Others, including blood and skin cells, are constantly dying and are therefore in need of replacement. At the earliest stages in our development, stem cells have the greatest capacity to produce a range of cell types. Researchers are seeking ways of using the regenerating power of stem cells to repair and replace the damage to tissues and organs caused by disease and ageing. STEM CELLS: POTENT RESEARCH PLEASE PHOTOCOPY AND DISTRIBUTE A human embryo, six days after fertilization At the earliest stages of develop- ment all of our cells are the same – unspecialized or ‘undifferentiated’, yet every one of our trillion cells originates from these. The importance of stem cells for medical researchers is clear. Stem cells provide a potential opportunity to treat some of the major diseases that affect human beings. Stem cells produce many different types of cell: (clockwise from top) nerves, blood cells, muscle and skin cells. New cells for old

Transcript of Lab Notes Stem Cells

Page 1: Lab Notes Stem Cells

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Every human being is made of a thousand million,million cells. Mostof these cells arehighly specialized.For instance, thereare nerve cells,blood cells andmuscle cells, all of which performspecific tasks.But where didthese specializedcells come from?

The precursors of all the differentkinds of cells anindividual has arecalled stem cells.

LabNotes

After a few cell divisions, many cells lose their ability to divide as theymake up the tissues and organs of the body, though some continue to bethe source of new cells for the remainder of our lives.The reason isstraightforward: some cells, such as those found in the brain, are createdearly on in development and are set for life. Others, including blood andskin cells, are constantly dying and are therefore in need of replacement.

At the earliest stages in our development, stem cells have the greatestcapacity to produce a range of cell types. Researchers are seeking ways ofusing the regenerating power of stem cells to repair and replace thedamage to tissues and organs caused by disease and ageing.

STEM CELLS: POTENT RESEARCHPLEASE PHOTOCOPY AND DISTRIBUTE

A human embryo, six days after fertilization

At the earlieststages of develop-ment all of ourcells are the same– unspecialized or‘undifferentiated’,yet every one of our trillion cells originatesfrom these.The importance of stem cells formedical researchersis clear. Stem cellsprovide a potentialopportunity totreat some of the major diseasesthat affect humanbeings.

Stem cells produce many different types of cell: (clockwise from top) nerves, bloodcells, muscle and skin cells.

New cells for old

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We are continually faced with a range of difficult decisions to makein our lives.The reason why some decisions are difficult to make isthat even though the options are clearly right or wrong, the rightchoice is not always the most attractive one. Other difficultdecisions are more complicated – with no clear ‘right’ or ‘wrong’.

Making these difficult decisions relies on the set of personal valuesthat we have developed during our lives and on the wider valuesheld by society enshrined in the law or sometimes religion.We referto these values, rules and the principles towhich they give rise as ethics.

Decision-making also relies onhaving access to informationand appreciating all sidesof the argument. Most of the issues coveredin LabNotes:New biologyand societyraise moraldilemmas thatare not easilysolved.

LabNotes new biology and society The Wellcome Trust2

The possibility that stemcells could be used torepair damaged tissues andorgans has created a greatdeal of interest amongmedical researchers.There are several potentialsources of stem cells foruse in such research.They could be:• obtained from the cells

of early embryos after aterminated pregnancy;

• harvested from theumbilical cords ofnewborn babies;

• obtained from some adult tissues such as bone marrow.There are obvious medical benefits to be gained from using

these cells, but there are also serious moral and ethical questionsto ask in relation to using stem cells from some of these sources.For example, is it acceptable to use the spare embryos fromfertility treatments?

Making difficult decisions

Stem cells are ‘master’ cells that give rise toother cells. Some organs and tissues, onceestablished, do not change or grow very muchand consequently need few active stem cells.Others, like blood and skin, need continuousreplacement throughout our lives and aredependent on a large supply of vigorouslydividing stem cells.

The earlier we go back in our development,the more able our stem cells appear to be atproducing new cells. A newly fertilized egg issaid to be ‘totipotent’ (literally, ‘all powerful’)because it is capable of producing all thekinds of specialized cells a new individualrequires. Every totipotent cell has thecapacity to develop into a new human being.

After three rounds of celldivision, however, the processof cell specialization or‘differentiation’ begins andcells lose some of theirpotential to diversify. Stemcells in embryos of 50–100cells are ‘pluripotent’ (‘pluri’meaning ‘many’), meaning thatthey can give rise to any tissuetype in the body, but not anew individual.Those stemcells derived from fetuses andmature humans are even lessversatile and are called‘multipotent’, that is giving riseto a range of cell types.

Ethical questions are raised from thediffering perspectives about the moral statusof a human embryo. There are those whobelieve that an embryo has the same moralstatus as a human being from the momentof its creation. Others consider that an earlyembryo is simply a collection of cells.The middle ground, on which the currentresearch uses are based, recognizes thespecial status of an embryo as a potentialhuman being but accepts that it is justified touse early embryos for serious researchpurposes which may benefit others.

If we were able to locate and use stemcells from adults, there would be fewerethical questions raised than in the use ofembryonic stem cells. Scientists have reportedthat, in the right environment, adult stem cellsfrom neural tissue can be made to produceblood cells, and blood stem cells can be madeto produce liver tissue. At present, scientistsare unsure exactly how versatile various kindsof adult stem cells are, or whether these cellscould be made more ‘potent’.

Are all stem cells alike?

Sources of stem cells

Red blood cells, which need to be continually replenished

A six-day-old human embryo,beginning to implant into the

lining of the uterus.

EM Unit, Royal Free Hospital School of Medicine/The Wellcome Trust Medical Photo Library

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The Wellcome Trust new biology and society LabNotes

The reason for carrying out research intostem cells is to find out whether it ispossible to make new cells and tissueto replace a person’s damaged tissue.

At first glance it may appear thatscientists simply need to take a few stemcells and produce cultures of different celltypes that could be stored and supplied ondemand. For example, insulin-producing cellscould be taken from a ‘tissue bank’, inserted into the pancreas of people with diabetes,enabling them to produce their own insulin.However if the stem cells are not geneticallycompatible with a person, their immune system will reject them.Cloning techniques may provide a solution to this problem. If theoriginal stem cell, from which the rest of the replacement cells aregrown, is genetically identical to the other cells of the recipient, thegrown cells would be seen as being his or her own cells and wouldnot be rejected.

Such cloning techniques raise ethical questions and it may occurat some point in the future that some cells are removed from anindividual at the embryo stage, cultured and stored for when thatindividual falls ill and needs replacement cells.

For the foreseeable future, however, a solution being exploredinvolves taking a nucleus of any body cell of a patient andtransplanting this into an egg cell that has had its nucleus removed.The stem cells within the embryo produced as a result would thenbe totipotent and could be guided into producing the desired cellsor tissue.This technique is called nuclear replacement.

The technique was used in 1997 by the scientists at the RoslinInstitute to produce a clone of an adult sheep, Dolly, and washeralded as a major breakthrough, in part because itdemonstrated the potential to grow new tissue in this way.

The ethical question in applying this technology to human stem cells is whether it is acceptable to produce an early embryo,a potential new human life, only to use it to produce a type oftissue for therapeutic purposes. Other ethical concerns relate to whether the development of a cloned human embryo is onlyone step away from a cloned human being.

What is the connectionbetween stem cells and cloning?

The same technique underlies therapuetic and reproductive cloning.

The word ‘clone’ is applied to many different entities in science.Originally it was used to describe genetically identical plantsproduced by asexual reproduction – a process gardeners exploitwhen they take cuttings. Plants are prolific in their ability tomake identical genetic copies of themselves, as are bacteria andmany other organisms. Such genetic copies are termed clones.

The only human clones that we have experience of areidentical twins.The recent usage of the term ‘cloning’ has beenlargely in reference to Dolly the sheep and other animals. Dollyand others were experiments to see whether animals that werebred to produce therapeutic substances, for example in theirmilk, could be recreated identically. (See LabNotes: New biologyand society Issue 1, ‘Downon the Pharm’.)

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What is a clone?

In the recent discussion about the development and use of cloning,some people have made the distinction between reproductivecloning and therapeutic cloning. Both use nuclear transfertechniques, but the outcomes are very different.• Therapeutic cloning, if successful, will lead to the production of

replacement cells and tissues that are genetically compatible withthe patient and so would not be rejected by the immune system.

• Reproductive cloning will produce a baby who would begenetically identical to one of his or her parents.

Implanting an embryo created by nuclear replacement into awoman’s womb is, and is likely to remain, a criminal offence in theUK. Nevertheless, some people believe that allowing therapeuticcloning to take place is the first step on the ‘slippery slope’ towardsreproductive cloning and should not be permitted on that basisalone.This view raises some clear ethical questions, such as:• Is it right to legalize a technology that may at some point in

the future be used for a purpose that is not socially desirable?• Is it right to prevent research that may lead to treatment and

cures of otherwise untreatable disease for fear that it may beused for a purpose that is not socially desirable?

Therapeutic andreproductive – two applications

of cloning technology

Frozen sperm, usedfor in vitro fertilization

Identicaltwins arenaturallyoccurringclones

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1997February: Scientists at the Roslin Instituteannounce the birth of Dolly the sheep, thefirst mammal to be cloned by nucleartransfer from adult cells.

October: Scientists at the University ofHawaii Medical School announce the birth of Cumulina, the first-born of 22 mice clonedby nuclear transfer technology. (Cumulinadied in May 2000, having raised two litters ofher own and having lived for 31 months –95 in mouse years.)

1998January: The Human Fertilisation andEmbryology Authority (HFEA) launches apublic consultation on issues raised bycloning technology.

November: Scientists at the University ofWisconsin announce the first ever extractionand culture of human embryonic stem cells(‘pluripotent’ cells that have the potential todevelop into any other cell in the body).

December: The HFEA publishesrecommendations based on the consultationbegun in January; the Government asks itsChief Medical Officer, Liam Donaldson, toconsider the issues.

1999October: UK Science Minister Lord Sainsburypublicly expresses support for a change in thelaw to permit stem-cell research on humanembryos “The important benefits which camefrom this research,” Lord Sainsbury said,“outweigh any other consideration one mighthave” – but the shadow health secretary,Dr Liam Fox, accused Lord Sainsbury of“sweeping away all the complex ethical issues[surrounding therapeutic cloning] with

complete contempt”. A British MedicalAssociation discussion paper suggests thatpublic hostility to human reproductive cloningmight be based on an ‘illogical and transientfear of a new technology’.

2000January: UK patents covering aspects of thenuclear transfer technology used to cloneDolly are granted to the parent companiesof Dolly’s creators.

April: The UK’s Nuffield Council onBioethics publishes its discussion paper‘Stem Cell therapy:The ethical issues’.

August: Publication of the report ofthe UK Chief Medical Officer’s ExpertGroup, entitled ‘Stem Cell Research:Medical Progress withResponsibility’, which made anumber of recommendations,including that stem-cell researchusing human embryos should bepermitted under the HumanFertilisation and Embryology(HFE) Act 1990.

A recent history of cloning and stem-cell technology in the UK

Dolly the sheep

Lord Sainsbury

Nuclear transfer: Moving a nucleus from bodycell to egg cell.

James King-Holmes/Science Photo Library

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December: Amendments to the HFE Act1990 to accommodate new research onhuman embryos (including stem-cellresearch) are debated in the House ofCommons and accepted by the majority.

2001January: House of Lords votes in favour of the additions to the HFE Act 1990.

April: The House of Lords Committee onStem Cell Research is set up to consider the scientific and ethical implications of the new legislation.

October: The Pro-Life Alliance challengesthe UK Department of Health in court overa loophole in the HFE Act 1990 that couldtechnically allow the reproductive cloning of human embryos – and wins the case.

November: The Department of Health’snewly drafted Human Reproductive Cloning Bill is approved by Parliament and effectively bans human reproductivecloning in the UK.The Bill receives RoyalAssent on 4 December 2001.

2002February: The House of Lords Committeeon Stem Cell Research publishes its report,which supports the use of human embryosin stem-cell research,produced either by invitro fertilization or bycell nuclearreplacement (cloning).

Meanwhile, othercountries acrossEurope and the USA,Canada and Australiacontinue to debatethe use of humanembryos for stem-cellresearch and basetheir decisions on arange of scientific,cultural, ethical andmoral considerations.

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Since the first ‘test-tube baby’, LouiseBrown (right), was born in Oldham,Lancashire on 25 July 1978, in vitrofertilization (IVF) has become anaccepted method of assisting coupleswho have difficulty conceiving children,even though they can produce healthysperm and eggs.

Despite some initial adverse reactionto the idea of IVF and the high cost –which may run to tens of thousands of pounds before an implanted embryois successfully carried to term – morethan 300 000 children have now beenproduced by this method in more than 40 countries. Before theextension of the Human Fertilisationand Embryology Act to include stem-cell research, more effective IVFtreatment was one area of researchthat was permitted for the spareembryos that the treatment produces.IVF involves the following stages:

• Drugs resembling follicle-stimulatinghormone stimulate multiple folliclesin the ovaries, each containing a single egg.

• A needle is guided into each follicle inthe ovary to remove the fluidcontaining the egg.The eggs arecollected into a test-tube.

• The eggs are then cultured in aspecial ‘growth medium’.They aresorted and later that day the sperm,following ‘preparation’, are placedwith them. In cases where there areproblems with motility of the sperm,each egg is injected with an individualsperm.This technique is calledintracytoplasmic sperminjection (ICSI).

• Embryos are placed into the uterususing a catheter, a hollow plastic tube.

• Progesterone, a natural hormone,helps the lining of the uterus developand support the pregnancy.Additionalprogesterone is given by injection,vaginal suppository, or vaginal gel.

In vitro fertilization

A doctor injecting a human sperm into an egg during in vitro fertilization

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The potential applications of growing new cells,tissues and even organs are numerous. However,if the techniques deliver their promise, the mostlikely beneficiaries would initially include peoplewith serious burns in need of skin grafts andpatients suffering from neurodegenerative diseases

such as Parkinson’s. People with diabetes couldbe treated so that their faulty insulin-secreting cells are replaced with functionalcells and sufferers of osteoporosis mightdevelop their own new bone cells.

The possibility of encouraging growthin the most specialized tissue of all – the neurons of the central nervous

system – offers a glimmer of hope to those who are paralysed from

spinal cord injuries.

Possible uses of tissue derived from stem cells totreat disease

Most people are concerned about thepossibility of cloning a human being.We prize individuality and we nowknow that variation within a species is a key to its survival. Some of our fearshave been fuelled by literary depiction of human clone drones or by newspaperscare stories.

There are, however, some peoplearound the world who would welcomethe possibility of reproductive cloning,since this is the only way they are likelyto be able to have children geneticallyrelated to themselves. A woman or aman who is infertile could have a bodycell nucleus, containing all of their geneticmaterial, transferred into an unfertilizedegg.This could then be implanted eitherin the woman’s own uterus or in theuterus of another woman.The resultingoffspring would be genetically identical to whichever parent donated the cell

nucleus in the first place.However, currently thistechnique is unrefined and would lead to a highincidence of embryo wastageand malformed embryos.

The European Conventionon Human Rights, which wasincorporated into UK law inOctober 2000, declares that“everyone has a right to found a family”. It is yet to be seenwhether people who would not be able to ‘found a family’ withoutthis technique will use the Articlefrom the European Convention to challenge the laws that currentlyprevent such an action.

Who wants to clone a human being?

Cells producing insulincould replace insulininjections for diabetics

LabNotes new biology and society The Wellcome Trust6

Cell type

Neural (nerve) cells

Heart muscle cells

Insulin-producing cells

Cartilage cells

Blood cells

Liver cells

Skin cells

Bone cells

Retinal (eye) cells

Skeletal muscle cells

Target disease

Stroke, Parkinson’s disease,Alzheimer’s disease, spinal cordinjury, multiple sclerosis

Heart attacks,congestive heart failure

Diabetes

Osteoarthritis

Cancer, immunodeficiencies,inherited blood diseases,leukaemia

Hepatitis, cirrhosis

Burns, wound healing

Osteoporosis

Macular degeneration

Muscular dystrophy

‘Heidi x: The true horror of cloning’,an artwork by Heidi Gray from theWellcome Trust’s exhibition ‘Multiplicity’

Who could benefit from stem-cell therapies?

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This section of LabNotes isdesigned to enhance students’• understanding of the issues involved;

• ability to form and defend theirown opinions about moral

and social issues on thebasis of evidence and

reasoned argument;• understanding of

the influence of the media on theunderstanding of new biologicaltechnologies.

The activityThis activity involves students

writing a newspaper ‘leader’ on thequestion of whether or not embryonicstem cell research should be allowed.

Students will be asked to:• choose a national or local newspaper

for which to write;• research the newspaper’s readership

and style;• identify and evaluate the arguments

for and against embryonic stem cellresearch;

• form their own opinion on whetherthis research should be permitted;

• defend their opinion in a leader writtenin the style of the newspaper they havechosen.

How to use this activityThis activity is flexible and can beadapted to your requirements.

Students will need• access to the internet

(for research purposes);• access to national and local

newspapers (including back copies).

PreparationYou might like to obtain newspaperreports of the debate leading up to the vote, details of the circulation and readership profile of a selection of national and local newspapers and the various governmental reports anddiscussion papers. Alternatively, studentsmight be asked to do this as part of theirresearch. Students will need photocopiesof the ‘Instructions to Students’ and thelist of further reading and information.

Further activities (optional)You could extend this activity by:• inviting the editor of a local newspaper

to talk to students about writingleaders and/or reporting on social andethical issues;

• inviting representatives from groupssupporting the different sides of thedebate to talk to students;

• using the leaders writtenas the basis for a formaldebate on the issues involved(this could be just the class or you could extend it morewidely);

• conducting an opinionpoll to see how the votewould have gone in theschool community;

• find out whether school governors (or parents) have any expertise thatcould contribute to the debate andasking them to share this expertisewith students.

On 19 December 2000, in a free vote MPs voted (366 to 174)to allow embryonic stem cell research under licence fromthe HFEA.The debate was fierce, with one side arguingthat this would be the slippery slope towards reproductivecloning, the other arguing that such research representedthe ‘only hope’ for people with certain disabilities.

Background for teachers

Getting to thestem of the argument

Subject areas and key skills

This activity is designed forstudents of the biological sciences,general studies, English, mediastudies and philosophy. It isrelevant to all students in the contribution made to:

• students’ spiritual, moral, socialand cultural development;

• teaching of citizenship andpersonal, social and healtheducation;

• key skills of communication,information technology, working with others (if groups are used) and problem solving;

• thinking skills of informationprocessing, reasoning, enquiry and evaluation skills.

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Choosing a newspaperThere are many different newspapers.Some of these are aimed at a nationalreadership, others are aimed at readers in a local area.

Each newspaper, whether national orlocal, has a certain ‘readership profile’.The readership profile of a newspaperidentifies the ‘typical reader’ of thatnewspaper. This reader might be male orfemale, come from a particular age groupand socio-economic class, be inclined tovote for the Right or the Left and belikely to have had a certain sort ofeducation and to pursue certain interestsor hobbies.The readership profile of anewspaper is important because thepeople who write for the newspaperneed to know for whom they are writingso they can anticipate what their readerswill be interested in, and what view theyare likely to take on it.

You can get details of readershipprofiles by contacting the advertisingdepartments of the various newspapers.

To choose which newspaper you wouldlike to write for, you will want to have alook at the various newspapers available.The school/college library may havecopies of some newspapers, but you mighthave to go to the local library for others.Alternatively you can read mostnewspapers online.

In choosing a newspaper for which towrite you might consider whether youwould prefer to:• have more or fewer words (remember

it is often harder to express anargument when you have to be concise,on the other hand you might preferthe challenge of having to express acomplicated argument very simply);

• write for a highly educated readershipor a less well educated one;

• write for a readership likely to holdstrong political or ethical views;

• write for a national audience or a localaudience (if you choose the latter youwill want to find a local ‘angle’ for yourargument).

Identifying and evaluatingthe arguments for andagainst the use of humanembryos for stem-cellresearch

An argument consists of a claim (the conclusion), together with one or more reasons for believing this claim (the premises). A good way of‘identifying an argument’ is to set it out in ‘logic book style’. The followingargument is set out logic book style:

Argument 1Premise 1: If it snows the mail will be latePremise 2: It is snowingConclusion:Therefore the mail will be late

Arguments are either good or badarguments. Argument 1 would be a good argument so long as we havereason to believe the premises. It is a good argument because if the premisesare true, the conclusion must be true. (It isimportant to note that this does not meanthat the premises are true, only that if theyare true, the conclusion must be true.) In a good argument the premises must not only be reasonably believed to betrue, taken together they must also providegood (but not necessarily conclusive)reason to believe the conclusion.

Instructions to students

You are asked to write a‘leader’ article for anational or localnewspaper – a newspaperarticle giving an editorialopinion.The leader article will be 150–650 words(depending on thenewspaper you choose),and it will contain anargument for or againstthe use of human embryosfor stem-cell research.

You will need to:• conduct research into the

different styles and readershipprofiles of various newspapers;

• decide which newspaper you willwrite for;

• conduct research into thearguments for and against the useof human embryos for stem-cellresearch;

• form your own opinion aboutwhether it is ethically permissibleto use human embryos for stem-cell research;

• identify your reasons for holdingthis opinion;

• express your opinion (togetherwith your reasons for holding it)in the style of the newspaper youhave chosen, and in such a waythat you might hope to convincethe readers of this newspaper toagree with you.

Books and journals and reportsAnthony Weston, A Rulebook for Arguments,Hackett, 2001 (ISBN 0 87 220552 5)

The Report of the Committee of Enquiry intoHuman Fertilisation and Embryology, chairedby Dame Mary Warnock (HMSO ISBN 0 10 193140 9)

The National Bioethics AdvisoryCommission, Ethical Issues in Human StemCell Research: Volume 1, 1999, and Volume 11(commissioned papers), 2000, Maryland USA

HGAC and HFEA, Cloning Issues inReproduction, Science and Medicine,DTI 1998

Further reading and sources of inform

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A bad argument is one in which thepremises are not reasonably believed to betrue, or one in which the premises, eventaken together, do not provide good reasonto believe the conclusion.The following is abad argument (even though it may look likethe good argument above):

Argument 2Premise 1: If it snows the mail will be latePremise 2: The mail is lateConclusion: Therefore it is snowing

This is a bad argument because even if thepremises are both true they provide us withno reason at all for believing the conclusion.The mail might be late because the mail vanhas broken down. (This argument is anexample of the fallacy of affirming theconsequent. Fallacies are bad arguments that look like good arguments.)

In order to evaluate the strength of theargument it is necessary to(i) ask whether the premises are true;(ii) decide whether the premises, taken

together, give good reason to believe the conclusion.

If you come to believe the premises are true,and that the premises give good reason tobelieve the conclusion, you have no rationalchoice other than to believe the conclusion.(If you don’t believe this look again at

argument one – could you believe thepremises without believing the conclusion?)

If you can argue that even one of thepremises is false, on the other hand, or thatthe premises, taken together, do not givegood reason to believe the conclusion, thenthe argument does not provide good reasonto believe the conclusion.

Formulating your own argumentThe box on ‘Further reading and sources ofinformation’ provides material to help identifyarguments both for and against the use ofhuman embryos in stem cell research.Youmay also find it helpful to refer to the viewsexpressed by MPs on pages 14 and 15. Makesure that you identify and evaluate at leastone argument for and at least one against.

Once you have identified and evaluated thearguments you will be in a position to formyour own opinion, and to formulate yourown argument for that opinion. Only you cando this because only you know which of thearguments seems to you – rationally speaking– to be stronger.

Doesn’t this make my argument subjective?It is important to note that this does notmake your argument ‘subjective’ because youare giving rationally persuasive reasons forbelieving what you believe. In making anargument for a claim you are saying that your conclusion is more than just your

opinion, you are sayingthat other people havereason to believe the claimyou are making.

Your leader article will bemore persuasive if, as well asgiving arguments for youropinion, you also give argumentsagainst what seems to you to bethe strongest argument against your ownposition. In doing this be careful not to set upa ‘straw man’, an easy argument to reject.Your aim is to make the strongest possiblecase for your own position by setting up, anddestroying the strongest possible argumentagainst your position.

You might find it easier to identify yourown argument if, once you think you knowwhat you believe, you set it out as anargument in logic book style.

Writing your leaderOnce you know what you believe, and why,you are in a position to write your leader.You will want to consider how to expressyour arguments in a way that is likely toconvince the typical reader of the newspaperthat you have chosen. Remember to stick to a reasonable word limit for the paper you have chosen, and to choose a headlinedesigned to grab the interest of the typical reader.

WebsitesNew Scientist: www.newscientist.com/hottopics/cloning/Institute of Biology: www.iob.org/Wellcome Library: http://library.wellcome.ac.uk/resources/ob_cloning.shtmlBBC: www.bbc.co.uk/science/genes/gene_safari/clone_zone/intro.shtmlDepartment of Health: www.doh.gov.ukThe Royal Society: www.royalsoc.ac.uk/policy/stem_cell_research1.htmNewspapers include:www.independent.co.uk/www.telegraph.co.ukwww.timesonline.co.uk/ www.mirror.co.uk/

Newspaper articlesThe Times:18 November 2000, P.14 ‘Commonstussle with morality of embryo research’

14 December 2000, letter ‘cloning treatslife as disposable’

16 December 2000 p.16 ‘Disabled MPsplead for stem cell research’ and p.8 ‘MPs pressured over human embryo vote’

20 December 2000 p.1 ‘MPs vote to allow cloning of human embryos’ p.2.‘MPstake leave of their senses and come alive’and p.10 ‘Passions run high in stem celldebate’.

ces of informationThe Guardian:16 December 2000, page 13,‘MPsagonise over matters of life and death,and p. 23 ‘Stem cells offer hope’The Sunday Telegraph:3 December 2000.‘Embryo cloning isacceptable, says C of E’The Mirror:20 December 2000, p.4 ‘Research onembryos OK’The Daily Mail:20 December 2000, p.2 ‘Scientists canclone human embryos after Commonsvote’

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HistoryIn 1984 the Committee of Enquiry intoHuman Fertilisation and Embryology (chairedby Dame Mary Warnock) recommendedthat research on human embryos should bepermitted only under licence. It stated thatresearch could take place only with the fullconsent of the couple who generated theembryo and within the first 14 days (afterwhich the embryo must be destroyed).

These recommendations led to theHuman Fertilisation and Embryology Act of 1990 which made it a criminal offence toexperiment on human embryos without alicence from the Human Fertilisation andEmbryology Authority. Such licences wouldbe granted only for research that is judgedto be necessary and desirable for one orother of the following purposes:• developing infertility treatments;• developing more effective techniques

of contraception;• developing methods of detecting the

presence of gene or chromosomeabnormalities in embryos beforeimplantation;

• acquiring an understanding of the causes of congenital diseases and miscarriages.

When the Act was made law, the use ofembryos for stem-cell research had not beenenvisaged (though their use in reproductivecloning had been).

In 1998, however, the Human Fertilisationand Embryology Authority (HFEA) and theHuman Genetics Advisory Committee(HGAC) recommended the addition ofthree further situations under whichlicences might be granted. Such research,argued the HFEA, would hold out thepromise of producing treatments for seriousdegenerative diseases such as Parkinson’sdisease and multiple sclerosis.

These extensions would be:• increasing knowledge about the

development of embryos;• increasing knowledge about serious

disease;

• developing methods of treatment for seriousdisease as a result of this knowledge.

It was this extension to the1990 Act for which MPsvoted on 19 December 2000 and was passed byParliament in January 2001.

EthicsThe arguments againstextending the purposes for which HFEA might grantlicences are, in brief, that:a) it is wrong to use any

human being (even apotential human being) asa means to an end, even if that end is the alleviationof human suffering;

b) to use human embryos forsuch purposes threatensto undermine our respectfor human life – it is but a short step from this to the use of fetuses, newbornbabies (etc.) as means to the end of thealleviation of suffering;

c) to permit stem-cell research on embryoswould be to permit therapeutic cloningand so to move further down the ‘slipperyslope’ towards reproductive cloning;

d) even if reproductive cloning continues to beillegal in this country, the knowledge gleanedfrom therapeutic cloning could be exportedand used elsewhere for such purposes;

e) such research is not necessary becausethe benefits to be derived from it canpotentially be achieved by other means(specifically by using adult stem cells).

The arguments for extending the purposesfor which HFEA might grant licences are, inbrief, that:a) it is wrong to allow suffering to continue

when it might be alleviated;b) it is unprincipled to permit research on

embryos for some purposes but not forothers;

c) the human embryo before the ‘primitivestreak’ stage (14 days after fertilization)

does not demand the full respectaccorded to a human person or even a human fetus;

d) even if adult cells can be used for someresearch purposes, the stem cells of theembryo are uniquely suited for othertypes of research;

e) reproductive cloning is, and will continueto be, illegal.There is no slippery slope;

f) it will be many years before scientists areable to make adult stem cells behave likeembryonic stem cells. Until this can beachieved, embryo stem cells provide theonly means of alleviating suffering.

Some of these arguments are forward-looking (they consider the consequencesof permitting such research), others arebackward-looking (they consider theintentions of those who do the research).

Others are based on the belief that certainacts should never be permitted whatevertheir consequences, and whatever theintentions with which they are carried out.

There is no reason why you shouldn’tcombine the different types of argument,so long as your overall position is coherent.

Theoretical background

A three-day-old embryo, fertilized in vitro. A hole has beenmade in the outer coat, so that a cell can be removed.The cell can then be tested to see whether the embryohas a genetic disease

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The Wellcome Trust new biology and society LabNotes 11

Natural selection has enabled ourbodies to cope with the wear and tearcaused by living, and to repair damage.Our understanding of science and itsapplications has increased our chancesof survival. For example, we know how to assist the natural skin healingprocess by keeping a wound free of infection or, in the case of largerwounds, by stitching the skin together.More advanced technology hassupplemented our natural repairprocesses as demonstrated by skingrafting, or in the case of brokenbones, the addition of metal pins and splints to promote repair.

TransplantationUp to now organ and tissuetransplantation have been among the most dramatic technologicalinterventions in the healing process.However, rejection by the immunesystem of the recipient has been themajor challenge to their success. Drugsthat suppress the host’simmune system go some way to preventingrejection, but they increasevulnerability toother infections.The severity ofthe immune

reaction can be minimized by improvingthe genetic match between the hostand the donor, so that the tissue isperceived by the body as less ‘foreign’.This is why close relatives are often thebest available donors, and why identicaltwins are ideal donors.The ultimate aimof therapeutic cloning is to enable anypatient in need of bodily repair toreceive genetically identical tissue.

Stem-cell-derived tissuesStem-cell researchers might eventuallybe able to establish banks of stem cellsmodified in such a way that they nolonger carry the biochemical markersthat trigger immune responses. If so,then it would no longer be necessaryto use therapeutic cloning techniquesto overcome the problem of rejectionfor tissue grafts and ultimately evenorgan donation.

Using cloned tissue to repair theeffects of a degenerative disease causedby a variant gene would be problematic

because the cloned cells wouldcarry the same genetic defect

as those they were replacing.Even though they wouldsuffer the same degen-erative process, continualrenewal of the tissue could slow down the

deterioration.

Giving nature’s repair process ahelping hand

Alexis Carrel (1873–1944) was the greatpioneer of the field of biotechnology whichincludes cloning and tissue-culture research.He carried out his earliest experiments in skingrafting in the 1890s, and attempted to growand maintain new tissue outside the body foruse in grafting and transplantation.

Carrel won the Nobel Prize for Physiologyor Medicine in 1912 for a method of suturingblood vessels, and pioneered the treatment ofwounds by antiseptic irrigation during WorldWar I, but his work in tissue-grafting andorgan transplantation never overcame theproblem of rejection.

He was the first to demonstrate thatanimals tolerated grafts from their owntissues, but rejected those from unrelatedanimals. Carrel was able to keep chicken heart cells alive for an incredible 28 years by regularly refreshing the solution they were bathed in.

Alexis Carrel

Alexis Carrel (right) with his perfusion apparatus,which maintained blood flow to a transplant organ

Jean-Loup Charmet/Science Photo Library

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Multiple sclerosis, Parkinson’s disease,leukaemia and osteoarthritis are diseasesthat cause great human suffering. Surely,therefore, we are morally required toalleviate this suffering by any meansavailable to us.

Or are we? Should we really be preparedto do anything to alleviate human suffering?If we think we should, then we are saying

that this end – the alleviation of humansuffering – will always justify the means,whatever the means. If this is right it meansthat so long as good will eventually comeof our actions, it does not matter whatthese actions are. But do we really want to say this?

Imagine a person – let’s call him James –who has been discovered to have a geneticmutation ensuring that his body contains asubstance that, when taken by someonewith any of the diseases mentioned above,cures them immediately and forever.There’sonly one problem: in order to ‘harvest’ thissubstance, James must be killed. Should we kill James to alleviate this suffering? Or would it be wrong to kill James despitethe fact that it would enable us to alleviatethis suffering?

This story is wildly implausible, of course,but it is designed only to stimulate thinkingabout whether we really do believe that we should do anything at all if doing it willalleviate human suffering.

There are many people who think thatan individual’s right to life overrides anygood we might otherwise do by killingthem.The philosopher Kant argued that it is always morally wrong to use anotherperson simply as a means to our own ends.Kant would certainly disapprove of killingJames in order to alleviate the suffering of others.

A Utilitarian, however, would argue thatwe should do whatever will produce thegreatest happiness of the greatest number.On the surface of it, therefore, a Utilitarianwould approve of killing James because inkilling him we would be bringing about thegreatest happiness of the greatest number.

Those who believe that the use of spareembryos, or the creation of new embryos,to obtain stem cells is morally wrongbelieve, like Kant, that even the alleviationof human suffering is not a good enoughreason to override others’ right to life.These people believe that a humanembryo, however it was created, has thesame moral status as a human being with aright to life that it is not morally permissibleto violate for any reason at all.Those whobelieve that the use of embryonic stemcells is morally acceptable, on the otherhand, believe either that the humanembryo does not have the same moralstatus as a human, with an unquestionableright to life, or that its right to life can beoverridden for the greater good.

It might seem that it is dangerous tobelieve that our right to life can beoverridden for the sake of a greater good.Such a belief might lead to the idea thatanyone can be sacrificed so long assomeone can argue that it was for thegreater good.

Usually, though, those who believe thatusing spare or created embryos to obtainstem cells is morally acceptable argue for it on the grounds that human embryos do

12 LabNotes new biology and society The Wellcome Trust

The ethics of embryonic stem-cell research

“Should we beprepared to doanything to alleviatehuman suffering?”

“The philosopherKant argued that itis always morallywrong to useanother personsimply as a means toour own ends”

“A Utilitarian wouldargue that we shoulddo whatever willproduce the greatesthappiness of thegreatest number”

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The actor Christopher Reeve, famous for playing the title role in the 1978 filmSuperman and its sequels, was paralysedfrom the neck down when his spine wasinjured in a horse riding accident in May1995. He has since become an ardentsupporter and fund-raiser for researchinto medical technologies of repair,showing great courage in defying thecrippling effects of his injuries andawesome resolution in expressing thehope that he may one day walk again.

Many people involved in accidents suffer paralysis as a result of severedneural connections, that prevent signalsfrom the brain getting through to thelimbs and may impair the function of otherorgans. Stem-cell research is one field ofresearch offering the possibility of bridging

the all-important gaps. In 1996 Reeve andphilanthropist Joan Irvine Smith establisheda research centre in the College ofMedicine at the University of California,Irvine.The Christopher Reeve ParalysisFoundation hasissued a positionstatementsupportingresearch on humanpluripotentstem cells.

not have a right to life because they havenot yet developed to the stage where theyhave acquired this right. Such embryos, theyargue, are not yet worthy of the moralrespect we undoubtedly accord to humanbeings at a later stage of development.We cannot deprive someone of a right

they do not (yet) have, so there can be no moral objection to experimenting on these embryos.

Such claims are appealing. After all,the embryos used for research purposesare merely clusters of cells with no organsor nervous system.They neither look nor act like human beings.They are notcapable of independent existence, theycannot make choices, feel fear, pain or pleasure, nor are they conscious.Surely to accord to this cluster of cells the right to life is to take the idea of theright to life to extremes?

On the other hand, if it is the lack of allthese properties that prevents these cellsfrom having a right to life, then anyone who is in a persistent vegetative statewould also have no right to life.

To one who believes that a human being, at every stage of development andhowever damaged, has the right to life thistoo would be unacceptable.

The question of whether the use ofembryonic stem cells or therapeutic cloningis morally permissible is not solved bypointing to the fact that these techniqueswill alleviate human suffering because thatsuggests that anything that alleviates humansuffering is morally and ethically permissible.Nor is it solved by appeal to the fact thatevery human being has a right to lifebecause it is neither obvious that theembryo has a right to life, nor that our rightto life cannot be overridden for the sake ofa greater good.

Questions regarding what is morallypermissible are clearly complex and noteasily answered.

The Wellcome Trust new biology and society LabNotes 13

Left: Rex FeaturesRight: Kobal Collections

Christopher Reeve: From Superman to spokesman

“Embryos, someargue, are not yetworthy of the moralrespect we accord to human beings at a later stage ofdevelopment”

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LabNotes new biology and society The Wellcome Trust14

1.Are you in favour of theamendments that were made to the 1990 Human Fertilisation andEmbryology Act, allowing humanembryonic stem cells to be used inresearch and for therapeutic cloning?

AB:Yes. I spoke in the debate in favour of changing regulations.

AW: No. I was opposed to the HumanFertilisation and Embryology (HFE) Act 1990 in so far as it allowed for thecreation, manipulation and destruction of early human life.

The 2001 amendments merely extendthe purposes of research under the HFEAct to include, amongst other things,‘increasing knowledge about the developmentof embryos’.The amendments for the first time allow pure research on embryoswithout reference to any clinical goals.This makes a mockery of the so-called‘special status’ of the human embryo.

2.When in your view does life beginand how did this influence your viewson the use of ES cells in research?

AB: I believe life does not truly begin until a fetus is able to sustain life outside themother’s body. However, I am happy thatthe HFEA places a limit of 14 days on anembryo used in research.

AW: Life begins at conception, the momentof the fusion of the human gametes (male sperm and female egg).This newhuman life, which comes into existence withthe formation of the one-cell zygote, has aninbuilt capacity to initiate, sustain, controland direct its own development.

As human life begins at conception andthe use of ES cells in research necessarilyinvolves the destruction of human embryos,I am completely opposed to such researchregardless of the scientific and medicalbenefits such research may bring.

3.What do you see as the mainethical issues surrounding the use of ES cells in research?

AB: I think the main ethical issue lies in the answer to the question as to when lifebegins. I argued in my House of Commonsspeech that anyone who already supportedthe use of embryos for research into suchthings as contraception, or is in support ofabortion, should also support the use ofembryonic stem cells in research into seriousdiseases. I found that most of those whowere arguing against the use of humanembryos in stem-cell research were the samepeople who would argue against abortionand against the use of embryos at any stageof the development in any research.

AW:a) The primary ethical issue is that the use

of ES cells in research involves destructiveresearch on human embryos.Thesehuman embryos are early human beingsand the amendments to the HFE Actintroduced in 2001 authorize their

Taking the vote – the dilemma faced by MPs

In 2000 MPs faced a free vote in the House of Commons on whether to allow changes to the 1990HFE Act.The vote split the House as MPs had to grapple with difficult moral and ethical questionsbefore they made their vote.Two MPs, one who voted for and one who voted against the changes,have outlined how they came to their decisions and shared some of their views about the use ofembryonic stem (ES) cells in research.

Anne Begg MP was born in1955 in Scotland and joined the Labour Party in 1983. Sheinherited the genetic conditionGaucher’s disease meaning that she uses a wheelchair.Her political interests includebroadcasting, genetic research,poverty and the oil industry.She voted in favour ofchanges to the 1990 Act.

Ann Winterton MP wasborn in 1941 and was

elected as a conservativeMP in 1983. Her political

interests include agriculture,education and healthcare.

She is Vice-Chairman of theAll-Party Parliamentary

Pro-Life Group. She votedagainst changes to the

1990 Act.

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The Wellcome Trust new biology and society LabNotes 15

destruction on a far larger scale than everbefore. Such research is wholly unethical.

b) If the embryonic stem cells used in research are created via cloningtechniques, as the 2001 amendments to the HFE Act purport to allow, thisrepresents the practice of asexualreproduction for the first time in humanhistory.We should not underestimatethe threat this poses to marriage,procreation and the nature of the family.

c) The use of ES cells in research carriesserious and unpredictable medical risks.It is unethical to expose patients tothese serious risks.

4. How did you weigh these ethicalissues against the potential benefits to human health when reaching yourdecision about the use of ES cells inresearch?

AB: I have always thought that the potentialbenefits to human health far outweigh anymoral or ethical considerations with regardto the use of embryonic stem cells inresearch. I believe such research has greaterpotential than say organ transplantation andmay in fact be the key to finally finding acure for some of the worst degenerativeconditions that at present debilitate somany people. However, I also believe suchresearch should be subject to tight andstringent controls.

AW: My ethical analysis is guided bytraditional medical ethics which requiresthat one must establish the moral integrityof a course of research independently of itspotential benefits. Certainly, one may weighthe benefits of a course of treatment againstthe disbenefits for a particular subject.But one may not weigh the disbenefits to the subject (in this case the embryo)against potential future benefits to others.

5. Is there in your view, an ethicaldifference between creating humanembryos specifically for stem-cellresearch and using embryos left overfrom fertility treatment?

AB:There is an ethical difference betweencreating human embryos specifically for

stem-cell research as opposed to usingthose left over from fertility treatment.However, I believe that it is even moreimportant to allow embryos to be createdthrough cell nuclear replacement because it is through this method the greatestpotential lies.Where stem cells createdthrough cell nuclear transplant from therecipient’s own cells are used, the chancesof rejection are lessened. It is this cloningtechnique which I believe will result in thegreatest medical advances and will have the greatest clinical application.

AW: In essence, no. All embryos, howevercreated, are entitled to the utmost respectin recognition of their inherent dignity asearly human beings.

I have always been completely opposedto the creation of ‘spare’ embryos in thecourse of infertility treatment such as IVF.The reason why such large numbers of‘spare’ embryos are created is because thesuccess rate of treatments like IVF remainsso poor (according to the HFEA AnnualReport 2000 the live birth rate was 18.2%).Therefore it is perceived that there is aneed to maximize the number of embryoscreated to maximize the chances of thetreatment being successful.

The Utilitarian argument that these‘spare’ embryos should be used fordestructive research perhaps in preferenceto embryos created specifically fordestructive research fails to recognize thatthe humanity of embryos entitles them to aminimum human respect, despite the cleardifferences between human embryos andolder human beings.

6. Do you have ethical concerns over the use of fetal stem cells forresearch, such as those obtainedfollowing abortions?

AB: I do have some ethical concerns aboutthe use of fetal stem cells but thoseconcerns are predominantly in the area of informed consent by the person who is providing the fetus.

AW:Yes I do.Where these cells have beenobtained as a result of the deliberatedestruction of human life through abortion

then the use of such cells is wholly unethical.Furthermore, there is the potential problemthat clinicians, in an attempt to obtain thesefetal cells, could encourage or provideincentives to pregnant women contemplatingabortion to proceed with their abortion.Women would be vulnerable to psychologicaland financial exploitation.

In any event, adult stem-cell researchcurrently shows more clinical promise thaneither embryonic or fetal stem-cell research.Adult stem-cell research combines scientificexcellence with best ethical practice and isa viable alternative that should be pursuedin preference to all other forms of stem-cell research.

7. Do you feel that there is a risk that the technology employed whenobtaining stem cells from embryoscreated using cloning methods couldlead the way to human reproductivecloning, in spite of the fact that atpresent most countries have in placelegislation to prevent it?

AB: It may be that somewhere in the world,an unethical scientist will try to clone ahuman being. However, I do not believe thatthey will be successful because they will beoperating, in most cases, outside the lawand outside the mainstream scientificcommunity.

AW:Again, yes, I do.The UK Governmenthas sought to make a clear distinctionbetween so-called ‘therapeutic’ (whichshould more accurately be termed‘experimental’) cloning and ‘reproductive’cloning and insists that the licensing ofexperimental cloning will not lead toreproductive cloning.

However, the terms ‘therapeutic’ and‘reproductive’ draw neither an ethical nor a scientific distinction.They refer simply tothe reasons for which a cloned embryo iscreated. In practical terms they are one andthe same process.The techniques thatwould be developed to allow cell nuclearreplacement to result in a healthy, dividinghuman embryo would be published ininternational journals and could then beused by ‘rogue’ scientists anywhere in theworld to produce a cloned baby.

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16 LabNotes new biology and society The Wellcome Trust

Writers: Brian Stableford, Peter Finegold,Marianne Talbot

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Editorial advisory board:Ms Victoria LezemoreDr Pauline Beattie Ms Sarah GinnsMs Nan DaviesMr Dean MaddenProfessor Richard Gardner

Next issue: Ageing

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In Colorado, USA, Molly Nash was born with Fanconi’sanaemia, a gene-related bone marrow disease thatthreatened her with early death. Molly’s parents, Jack andLisa, took advantage of IVF techniques and geneticscreening to make sure that their second child,Adam,would not have the same disease.

They took further advantage of the opportunity toselect an embryo by choosing one whose tissuesmatched Molly’s, so that stem cells recovered fromAdam’s umbilical cord might be used in treating Molly’scondition, thus increasing her chances of survivalconsiderably.

Adam was born in October 2000 amid debate as towhether it was ethical to select an embryo for thebenefits it can give, especially when that individual cannotgive consent to being used in this way. Concerns werealso raised over the number of embryos that wereproduced before a suitable match was found – over 100embryos were produced in total.

Adam Nash:The right cord

Top: Molly NashBottom:Adam Nash

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