Lab Notes Stem Cells

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LabNotes 3  JA NUA RY 20 03

new biology and society


At the earliest

being is made of

stages of develop-

a thousand million,

ment all of our 

million mill ion cells. Most

cells are the same

of these cells are

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highly specialized.


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are nerve cells,

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blood cells and

cells originates

muscle muscl e cells, all

from these.

of which perform

The importance

specific tasks.

of stem cells for 

But where did

medical researchers

these specialized

is clear. clear. Stem cells

cells come from?

provide prov ide a potential

The precursors

opportunity to

of all the different

treat some of

kinds of cells an

the major diseases

individual has are

that affect human

called stem cells. cells.


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

New cells for old After a few cell divisions, many cells lose their ability ability to divide as they  make up the tissues and organs of the body, body, though some continue continue to be  the source of new cells for the remainder of our lives.The reason is straightfor straig htforward: ward: some cells, cells, such as those those found in the brain, are created created early on in development development and are set for life. life. Others, including blood blood and skin cells, are constantly dying and are therefore therefore in need of replacement. At the earliest stages in our development, development, stem cells have have the greatest capacity to produce a range of cell types. types. Researchers are seeking 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.

A human embryo, six days after fertilization


Sources of stem cells The possibility that stem cells could be used to repair damaged tissues and organs has created a great deal of interest among medical researchers. There are several potential sources of stem cells for  use in such research. They could be: • obtained from the cells of early embryos after a  terminated pregnancy;

A six-day-old human embryo, beginning to implant into the lining of the uterus.

• harvested from of  the umbilical cords newborn 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 questions  to ask in relation to using stem cells from some of these sources. For example, is it acceptable to use the spare embryos embryos from fertility treatments?

Making difficult decisions  We are continually continually faced with a range of difficult decisions to make in our lives.The reason why some decisions are difficult to make is  that even though the options are clearly right or wrong, the right choice is not always always the most attractive one. one. Other difficult difficult decisions are more complicated – with no clear ‘right’ or ‘wrong’. ‘wrong’. Making these difficult decisions relies on the set of personal values  that we have have developed developed during our lives and and on the wider values held by society enshrined in the law or sometimes religion. We refer   to these values, values, rules and the principles principles to which they give rise as ethics. Decision-making Decision-maki ng also relies on having access to information and appreciating all sides of the issues argume argument. nt. Most of the covered in LabNotes: New biology  and society  raise moral dilemmas that are not easily  solved.

Are all stem cells alike? Stem cells are ‘master’ cells  that give give rise to other cells. cells. Some organs organs and tissues, tissues, once established, do not change or grow very much and consequently need few active stem cells. Others, like blood and skin, skin, need continuous replacement throughout our lives and are dependent on a large supply of vigorously  dividing stem cells.

The earlier we go back in our development,  the more able our stem cells appear to be at producing new cells. cells. A newly fertilized egg is said to be ‘totipotent’ (literally (literally,, ‘all powerful’) because it is capable of producing all the kinds of specialized cells a new individual requires. Every totipotent cell has the capacity to develop into a new human being. After three rounds of cell division divi sion,, howe however ver,, the proce process ss of cell specialization or  ‘differentiation’ begins and cells lose some of their  potential to diversify. diversify. Stem cells in embryos of 50–100 cells are ‘pluripotent’ (‘p (‘plur luri’i’ meaning ‘many’), meaning that  they can give rise to any tissue  type in the body, but not a new individual.Those stem cells derived from fetuses and mature humans are even less versatile and are called ‘multipotent’, that is giving giving rise rise Red blood cells, which need to be continually replenished  to a range r ange of cell types. EM Unit, Royal Free Hospital School of Medicine/The Wellcome Wellcome Trust Medical Photo Library 


LabNotes new biology and society The Wellcome Trust

Ethical questions are raised from the differing perspectives about the moral status of a human embryo. There are those who believe that an embryo has the same moral status as a human being from the moment of its creation. creation. Others consider that an early  embryo is simply a collection of cells. The middle ground, on which the the current research uses are are based, recognizes the the special status of an embryo as a potential human being but accepts that it is justified to use early embryos for serious research purposes which may benefit others. If we were able to locate and use stem would be fewer  fewer  cells from adults, there would ethical questions raised than in the use of  embryonic stem cells. Scientists have repor reported ted  that, in the right right environmen environment, t, adult stem stem cells cells from neural tissue can be made to produce blood cells, and blood stem cells can be made  to produce produce liver liver tissue. tissue. At present, present, scien scientists tists are unsure exactly how versatile various kinds of adult stem cells are, or whether these cells could be made more ‘potent’.


 Whatstem is the connection between cells and cloning? The reason for carrying out research into stem cells is to find out whether it is possible to make new cells and tissue  to replace a person’s damaged tissue. At first glance it may appear that scientists simply need to take a few stem cells and produce cultures of different cell  types that that could be be stored and and supplied supplied on demand. deman d. For example, insu insulin-p lin-producin roducingg cells could be taken from a ‘tissue ‘tissue bank’, inserted Frozen Fro zen sperm, used into the pancreas of people with diabetes, for in vitro fertilization enabling them to produce their own insulin. However if the stem cells are not genetically compatible with a person, their immune system will reject reject them. Cloning techniques may may provide a solution to this this problem. If the original stem cell, from which the rest of the replacement cells are grown, is genetically identical to the other cells of the the recipient, the grown cells would be seen as being his or her own cells and would not be rejected. Such cloning techniques raise ethical questions and it may occur  at some point in the future that some cells are removed from an individual at the the embryo stage, cultured and stored stored for when that individual falls ill and needs replacement cells. For the foreseeable foreseeable future, howev however er,, a solution being explored explored involves taking a nucleus of any body cell of a patient and  transplanting  transplant ing this into an egg cell cell that has had its nucleus nucleus removed. removed. The stem cells within the embryo produced as a result would then be totipotent and could be guided into producing the desired cells or tissue.This technique is called nuclear replacement. The technique was used in 1997 by the scientists at the Roslin Institute to produce a clone of an adult sheep, sheep, Dolly Dolly,, and was heralded as a major major breakthrough, breakthrough, in part because it demonstrated 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 human life, only to use it to produce produce a type of   tissue for therapeutic purposes. Other ethical concerns relate  to whether the development of a cloned human embryo is only  one step away from a cloned human being. The same technique underlies therapuetic and reproductiv reproductive e cloning.

 What is a clone? The word ‘clone’ is applied to many different entities in science. Originally it was used to describe genetically identical plants produced by asexual reproduction – a process gardeners exploit when they take cuttings. Plants are prolific in their ability to make identical genetic genetic copies of themselves, as are bacteria and many other organisms. Such genetic copies are termed clones. clones. The only human clones that we have experience of are identical twins.The recent usage of the term ‘cloning’ has been largely in reference reference to Dolly the sheep and other animals. Dolly and others were experiments to see whether animals that were bred to produce therapeutic therapeutic substances, for example in their LabNotes: tes: New biology  milk, could be recreate recreated d identically. identically. (See LabNo and society Issue 1,‘Down on the Pharm’.)

Identical twins are naturally occurring clones

Therapeutic and reproductive – two applications of cloning technology In the recent discussion about the developmen developmentt and use of cloning, some people have made the distinction between reproductive cloning and therapeutic cloning. Both use nuclear transfer  transfer   techniques, but the outcomes are very different. • Therapeutic cloning, cloning, if successful, will lead to the production production of  replacement cells and tissues that are genetically compatible with  the patient and so would not be rejected by the immune system. • Reproductive cloning will produce a baby who would be genetically identical to one of his or her parents. Implanting an embryo created by nuclear replacement into a woman’ss womb is, and is likely woman’ likely to remain, a criminal offence in the UK. Nevertheless, some people people believe believe that that allowing allowing therapeutic therapeutic cloning to take place is the first step on the ‘slippery slope’ towards reproductive cloning and should not be permitted on that basis alone.This alone. This view raises some clear ethical questions, questions, such as: • Is it right to legalize a technology that may at some point in  the future be used for a purpose pur pose 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 be used for a purpose that is not socially desirable? The Wellcome Trust new biology and society LabNotes



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

1998  January: The Human Fertilisation and Embryology Authority (HFEA) launches a public consultation on issues raised by  cloning technology. November: Scientists at the University of   Wisconsin announce the first ever extraction and culture of human embryonic stem cells (‘pluripotent’ cells that have have the potential potential to develop into any other cell in the body).

Dolly the sheep Lord Sainsbury


complete contempt”.A contempt”. A British Medical Medical Association discussion paper suggests that public hostility to human reproductive cloning might be based on an ‘illogical and transient fear of a new technology’.

February: Scientists at the Roslin Institute announce the the birth of Dolly the sheep, sheep, the first mammal to be cloned by nuclear   transfer from adult cells. October: Scientists at the University of  Hawaii Medical School announce the birth of Cumulina, Cumulina, the first-born of 22 mice cloned by nuclear transfer technology. technology. (Cumulina died in May 2000, having raised two two litters of  her own and having lived for 31 months –  95 in mouse years.)

Nuclear transfer: Moving a nucleus from body cell to egg cell.  James King-Holmes/Science Photo Librar y 

December: The HFEA publishes recommendations based on the consultation begun in January; January; the Government Government asks its its Chief Medical Medical Officer Officer,, Liam Donaldson, to consider the issues.

1999 October: UK Science Minister Lord Sainsbury  publicly expresses support for a change in the law to permit stem-cell research on human embryos “The important benefits which came from this research,” research,” Lord Sainsbury said, “outweigh any other consideration one might have” – but the shadow health secretary, Dr Liam Fox, accuse accused d Lord Sainsbury Sainsbury of  “sweeping away all the complex ethical issues [surrounding therapeutic cloning] with 4

LabNotes new biology and society The Wellcome Trust

2000  January: UK patents covering aspects of the nuclear transfer technology used to clone Dolly are granted to the parent companies of Dolly’s creators. April: The UK’s Nuffield Council on Bioethics publishes its discussion paper  ‘Stem Cell therapy:The ethical issues’. August: Publication of the report of   the UK Chief Medical Officer’s Expert Group, entit entitled led ‘Stem ‘Stem Cell Resea Research: rch: Medical Progress with Responsibili Respon sibility’, ty’, which made a number of recommendations, including that stem-cell research using human embryos should be permitted under the Human Fertilisation and Embryology  (HFE) Act 1990.


In vitro

December: Amendments to the HFE Act 1990 to accommodate new research on human embryos (including stem-cell research) are debated in the House of  Commons and accepted by the majority majority..

2001  January: House of Lords votes in favour of the additions to the HFE Act 1990. April: The House of Lords Committee on Stem Cell Research is set up to consider  the scientific and ethical implications implications of  the new legislation. October: The Pro-Life Alliance challenges  the UK Department Depar tment of Health in cour t over  a loophole in the HFE Act 1990 that could  technically allow the reproductive reproductive cloning of human embryos – and wins the case. November: The Department of Health’s newly drafted Human Reproductive Cloning Bill is approved by Parliament and effectively bans human reproductive cloning in the UK.The Bill receives Royal Assent on 4 December 2001.

2002 February: The House of Lords Committee


Since the first ‘test-tube baby’, Louise Brown (right), (right), was born in Oldham, Oldham, Lancashire on 25 July 1978, in vitro fertilization (IVF) has become an accepted method of assisting couples who have difficulty conceiving children, even though they can produce healthy sperm and eggs. Despite some initial adverse reaction to the idea of IVF and the high cost –  which may run to tens of thousands of pounds before an implanted embryo is successfully carried to term – more than 300 000 children haveinnow have been produced by this method more than 40 countries. countries. Before the extension of the Human Fertilisation and Embryology Act to include stemcell research, research, more effective effective IVF treatment was one area of research that was permitted for the spare embryos that the treatment produces. IVF involves the following stages: • Drugs resembling follicle-stimulating follicle-stimulating hormone stimulate multiple follicles in the ovaries, ovaries, each containing a single egg. • A needle is guided into each follicle in the ovary to remove the fluid containing the aegg.The eggs are collected into test-tube.

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• The eggs are then cultured in a special ‘growth medium’.They are sorted and later that day the sperm, following ‘preparation’, are placed with them. In cases where where there are problems with motility of the sperm, each egg is injected with an individual sperm.This technique is called intracytoplasmic sperm injection (ICSI). • Embryos are placed into the uterus using a catheter, catheter, a hollow plastic tube. • Progesterone, Progesterone, a natural hormone, helps the lining of the uterus develop and support the pregnancy.Additional progesterone progester one is given injection, vaginal suppository suppository, , orby vaginal gel.

on Stem Cell Research publishes its report, which supports the use of human embryos in stem-cell research, produced either by in vitro fertilization or by  cell nuclear  replacement (cloning). Meanwhile, Mean while, other  countries across Europe and the USA, Canada and Australia continue to debate  the use of human embryos for stem-cell research and base  their decisions on a range of scientific, cultural, cultu ral, ethi ethical cal and moral considerations.

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A doctor injecting a human sperm into an egg during

in vitro


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The Wellcome Trust new biology and society LabNotes



 Who wants to clone a human being? Most people are concerned about the nucleus in the first place. possibility of cloning a human being. However,, currently this However  We  W e prize individuality and we now  technique is unrefined unrefined know that variation within a species is and would lead to a high a key to its survival. survival. Some of our our fears incidence of embryo wastage have been fuelled by literary depiction and malformed embryos. of human clone drones or by newspaper  The European Convention scare stories. on Human Rights, which was There Ther e are, how however ever,, some people people incorporated into UK law in around the world who would welcome October 2000, declares that  the possibility of reproductive cloning, “everyone has a right to found since this is the only way they are likely  a family”. It is yet yet to be seen  to be able to have children genetically whether people who would not . A woman wom or a related toisthemselves man who infertile could haveana body  cell nucleus, nucleus, containing all of their their genetic material, transferred into an unfertilized unfertilized egg.This could then be implanted either  in the woman’s own uterus or in the uterus of another woman.The resulting offspring would be genetically identical  to whichever parent donated the cell

be able to ‘found family’  this technique willause the without Article Ar ticle from the European Convention  to challenge the laws that currently  prevent such an action. ‘Heidi x: The true horror horror of cloning’, an artwork by Heidi Gray from the  Wellcome  W ellcome Trust’s exhibition ‘Multiplicity’

 Who could benefit from stem-cell therapies? The potential applications of growing new cells,  tissues and even organs are numerous. However However,, if the techniques techniques deliver their their promise, the most likely beneficiaries would initially include people with serious burns in need of skin grafts and patients suffering from neurodegenerativ neurodegenerative e diseases such as Parkinson’s. Parkinson’s. People with with diabetes could be treated so that their faulty insulinsecreting cells are replaced with functional f unctional cells and sufferers of osteoporosis might develop their own new bone cells. The possibility of encouraging growth in the most specialized tissue of all –  the neurons of the central ner vous system – offers a glimmer of hope  to those who are paralysed par alysed from spinal cord injuries.

Cells producing insulin could replace insulin injections for diabetics


LabNotes new biology and society The Wellcome Trust

Possible uses of tissue derived from stem cells to treat disease Cell type

Target disease

Neural (nerve) cells

Stroke, Parkinson’s disease, Alzheimer’s disease, spinal cord injury, multiple sclerosis

Heart muscle cells

Heart attacks, congestive heart failure

Insulin-producing Insulin-produ cing cells


Cartilage cells


Blood cells

Cancer, immunodef Cancer, immunodeficiencies, iciencies, inherited blood diseases, leukaemia

Liver cells

Hepatitis Hepat itis,, cirrho cirrhosis sis

Skin cells

Burns, woun wound d healing

Bone cells


Retinal (eye) cells

Macular degeneration

Skeletal muscle cells

Muscular dystrophy 


Getting to the stem of the argument Background for teachers On 19 December 2000, in a free vote MPs voted voted (366 to 174) to allow embryonic stem cell research under licence from the HFEA.The debate was was fierce, with one side arguing that this would be the slippery slope towards reproductive reproductive cloning, the other arguing that such research research represented represented the ‘only hope’ for people with certain cer tain disabilities. This section of LabNotes is designed to enhance students’ • understanding of the issues involved; • ability to form and defend their own opinions about moral and social issues on the basis of evidence and reasoned argument; • understanding of  the influence of the media on the understanding of new biological technologies.

The activity This activity involves students writing a newspaper ‘leader’ on the question of whether or not embryonic stem 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 cell research; • form their own opinion on whether   this research should be permitted; • defend their opinion in a leader written in the style of the newspaper they have chosen.

How to use this activity This activity is flexible and can be adapted to your requirements.

Students will need • access to the internet (for research purposes); • access to national and local newspapers (including back copies).

Preparation You might like to obtain newspaper  reports of the debate leading up to  the vote, vote, detai details ls of the circulati circulation on and readership profile of a selection of national and local newspapers and  the various various government governmental al reports and discussion discus sion papers. Alterna Alternativel tivelyy, stude students nts might be asked to do this as part of their  research. resear ch. Stude Students nts will will need photoc photocopies opies of the ‘Instructions to Students’ and the list of further reading and information.

Subject areas and key skills This activity is designed for students of the biological sciences, general gener al studies, studies, Engli English, sh, media studies and philosophy philosophy. It is relevant to all students in the contribution made to: • students’ students ’ spiritual, spiritua l, mora moral, l, socia sociall and cultural development; developme nt; • teaching of citizenship and personal, social and health education; • key skills of communication, information technology, technology, working with others (if groups are used) and problem solving; • thinking skills of information processi pro cessing, ng, rea reasonin soning, g, enquiry and evaluation skills.

Further activities (optional) You could extend this activity by: • inviting the editor of a local newspaper   to talk to students about writing leaders and/or reporting on social and ethical issues; representatives from groups • inviting representatives supporting the different sides of the debate to talk to students; • using the leaders written as the basis for a formal debate on the issues involved (this could be just the class or you could extend it more widely); • conducting an opinion poll to see how the vote would have gone in the school community;

• find out whether school governors (or parents) have any expertise that could contribute to the debate and asking them to share this expertise with students.



Instructions to students Choosing a newspaper  You are asked to write a ‘leader’ article for a national or local newspaper – a newspaper  article giving an editorial opinion.The leader article  will be 150–650 words (depending on the newspaper you choose), and it will contain an argument for or against the use of human embryos for stem-cell research.

You will need to: • conduct research into the different styles and readership profiles of various newspapers; • decide which newspaper you will write for; • conduct research into the arguments for and against the use of human embryos for stem-cell research; • form your own opinion about whether it is ethically permissible to use human embryos for stemcell research; • identify your reasons for holding this opinion; • express your opinion (together with your reasons for holding it) in the style of the newspaper you have chosen, and in such a way that you might hope to convince the readers of this newspaper to agree with you.

There are many different newspapers. Some of these are aimed at a national readership, others are aimed at readers in a local area. Each newspaper, newspaper, whether national or  local, has a certain ‘readership profile’. The readership profile of a newspaper identifies the ‘typical reader’ of that newspaper. This reader might be male or  female, come from a particular age group and socio-economic socio-economic class, be inclined to vote for the Right or the Left and be likely to have had a certain sort of  education and to pursue certain interests or hobbies.The readership profile of a newspaper is important because the people who write for the newspaper  need to know for whom they are writing so they can anticipate what their readers will be interested interested in, and what view they  are likely to take on it. You can get details of readership profiles by contacting the advertising departments of the various newspape newspapers. rs. To choose which newspaper you would like to write for, you will want to have a look at the various newspapers available. The school/college library may have copies of some newspapers, but you might have to go to the local library for others. Alternatively you can read most newspapers online. In choosing a newspaper for which to write you might consider whether you would prefer to: • have more or fewer words (remember  it is often harder to express an argument when you have to be concise, on the other hand you might prefer   the challenge of having to express a complicated argument very simply); • write for a highly educated readership or a less well educated one; • write for a readership likely to hold strong political or ethical views; • write for a national audience or a local audience (if you choose the latter you will want to find a local ‘angle’ for your  argument).


LabNotes new biology and society The Wellcome Trust

Identifying and evaluating the arguments for and against the use of human embryos for stem-cell research An argument consists of a claim (the conclusion), conclusion), together with one or more reasons for believing this claim (the premises). premises). A good way of  ‘identifying an argument’ argument’ is to set it out in ‘lo ‘logic gic book book style style’.’. The following argument is set out logic book style:

Argument 1

Premise 1: If it snows the mail will be late Premise 2: It is snowing Conclusion: Therefore the mail will be late Arguments are either good or bad arguments. Argument 1 would would be a good argument so long as we have reason to believe believe the premises. premises. It is a good argument because if the premises are true, the conclusi conclusion on must must be true. (It is important to note that this does not mean  that the the premises premises are true, only that that if they  are true, the conclusion conclusion must must be true.) In a good argument the premises must not only be reasonably believed to be  true, tak taken en toget together her they they must must also also prov provide ide good (but not necessarily conclusive) reason to believe the conclusion.

Further reading and sources of  Books and journals and reports Anthony Weston, A Rulebook for Arguments Arguments, Hackett, 2001 (ISBN 0 87 220552 5) The Report of the Committee of Enquiry into Human Fertilisation and Embryology, chaired by Dame Mary Warnock Warnock (HMSO ISBN 0 10 193140 9) The National Bioethics Advisory Advisory Commission, Ethical Issues in Human Stem Cell Research: Volume 1, 1999, and Volume 11 (commission (comm issioned ed papers), 2000, Maryland USA HGAC and HFEA, Cloning Issues in Reproduction, Repro duction,Scienc Sciencee and Medicin Medicinee, DTI 1998


A bad argument is one in which the premises are not reasonably believed to be  true, or one in which the premises, even  taken together, together, do not provide good reason  to believe the conclusion.The following is a bad argument (even though it may look like  the good argument above):

In order to evaluate the strength of the argument it is necessary to (i) ask whethe whetherr the premis premises es are true; (ii) decid decide e whether whether the premises, premises, take taken n  together,, give good reason to believe  together  the conclusion. If you come to believe believe the premise premisess are true, and that the premises give good reason to believe the conclusion, conclusion, you have no rational

opinion, you are saying saying  that other people have reason to believe the claim you are making. Your leader ar ticle will be more persuasive if, as well as giving arguments for your  opinion, you also also give arguments against what seems to you to be  the strongest argument against your own Formulating your own argument position. In doing this be careful not to set up The box on ‘Further reading and sources of  reject. information’ provides material material to help iidentify  dentify  a ‘straw man’, an easy argument to reject. Your aim is to make the strongest possible arguments both for and against the use of  case for your own position position by setting setting up, and human embryos in stem cell research.Y research. You destroying the strongest possible argument may also find it helpful to refer to the views expressed by MPs MPs on pages 14 and 15. Make against your position. You might find it easier to identify your  sure that you identify and evaluate at least own argument if, once you think think you know one argument for and at least one against. what you believe, believe, you set it out as an Once you have identified and evaluated the argument in logic book style. arguments argumen ts you will be in in a position to form your own opinion, opinion, and to formulate your  your  own argument for that opinion. opinion. Only you can  Writing your leader  do this because only you know which of the Once you know what you believe, believe, and why, why, arguments seems to you – rationally speaking you are in a position to write your leader. leader.  – to be stronger stronger.. You will want to consider how to express your arguments in a way that is likely to Doesn’t this make my argument subjective? convince the typical reader of the newspaper  It is important to note that this does not  that you have chosen. Remember to stick make your argument ‘subjective’ ‘subjective’ because you  to a reasonable word limit for the paper are giving giving rationally persuasive reasons reasons for  you have have chosen, and to choose a headline headline believing what you you believe. In making an designed to grab the interest of the

choice other than to believe the conclusion. (If you don’t believe this look again at

argument for a claim you are saying that your conclusion is more than just your 

Argument 2 Premise 1: If it snows the mail will be late Premise 2: The mail is late Conclusion: Therefore it is snowing This is a bad argument because even if the premises both they provide us with no reasonare at all fortrue believing the conclusion. The mail might be late because the mail van has broken down. (This argument is an example of the fallacy of affirming the consequen conse quent. t. Fall Fallacies acies are are bad arguments arguments  that look like good arguments.)

argument one – could you believe the premises without believing the conclusion?) If you can argue that even one of the premises premi ses is false, false, on the other other hand, or that  the premises, taken together, together, do not give good reason to believe believe the conclusion, conclusion, then  the argument does not provide good reason  to believe the conclusion.

 typical reader. reader.

information  Websites  Websites New Scientist: Institute of Biology: Wellcome Library: resources/ob_cloning.shtml BBC: www.b nce/genes/gene_safari/ afari/ clone_zone/intro.shtml Department of Health:  The Royal Society: stem_cell_research1.htm Newspapers include:

Newspaper articles The Times: 18 November 2000, P.14 ‘Commons tussle with morality of embryo research’ 14 December 2000, letter ‘cloning treats life as disposable’ 16 December 2000 p.16 ‘Disabled MPs plead for stem cell research’ and p.8 ‘MPs pressured over human embryo embr yo vote’ 20 December 2000 p.1 ‘MPs vote to allow cloning of human embryos’ p.2.‘MPs take leave of their senses and come alive’ and p.10 ‘Passions run high in stem cell debate’.

The Guardian: 16 December December 2000, page 13,‘MPs agonise over matters of life and death, and p. 23 ‘Stem cells offer hope’ The Sunday Telegraph: 3 December 2000.‘Embryo cloning is acceptable, accept able, say sayss C of E’ The Mirror: 20 December 2000, p.4 ‘Research on embryos OK’ The Daily Mail: 20 December 2000, p.2 ‘Scientists can clone human embryos after Commons vote’

The Wellcome Trust new biology and society LabNotes



Theoretical background History In 1984 the Committee of Enquiry into Human Fertilisation and Embryology (chaired by Dame Mar y Warnock) Warnock) recommended  that research on human embryos should be permitted only under licence. It stated that research could take place only with the full consent of the couple who generated the embryo and within the first 14 days (after  which the embryo embr yo must be destroyed). These recommendations led to the Human Fertilisation and Embryology Act Act of 1990 which made it a criminal offence to experiment on human embryos without a licence from the Human Fertilisation and Embryology Authority. Authority. Such licences would be granted only for research that is judged  to be necessary and desirable for one or  other of the following purposes: • developing infertility treatments; • developing more effective techniques of contraception; • developing methods of detecting the presence of gene or chromosome abnormalities in embryos before implantation; • acquiring an understanding of the causes of congenital diseases and miscarriages.  When the Act was made law, law, the use of  embryos for stem-cell research had not been envisaged (though their use in reproductive cloning had been). In 1998, howeve howeverr, the Human Fertilisation and Embryology Authority (HFEA) and the Human Genetics Advisory Committee (HGAC) recommended the addition of  three further situations under which licences might be granted. Such research, argued the HFEA, HFEA, would hold out the promise of producing treatments for serious degenerative diseases such as Parkinson’ Par kinson’ss disease and multiple sclerosis. These extensions would be: • increasing knowledge about the development developme nt of embryos; • increasing knowledge about serious disease;


LabNotes new biology and society The Wellcome Trust

• developing methods of treatment for serious disease as a result of  this knowledge. It was this extension to the 1990 Act for which MPs voted on 19 December 2000 and was passed by  Parliament in January 2001.

Ethics The arguments against extending the purposes for which HFEA might grant licences lice nces are, in brief, brief, that that:: a) it is wrong to use any  human being (even a potential human being) as even en a means to an end, ev A three-day-old three-day-old embryo, fertilized in vitro. A hole has been if that end is the alleviation made in the outer coat, so that a cell can be removed. removed. of human suffering; The cell can then be tested to see whether the embryo b) to use human embryos for  has a genetic disease such purposes threatens  to undermine our respect does not demand the full respect  – it is but a short step for human life accorded to a human person or even from this to the the use of fetuses, fetuses, newborn a human fetus; babies (etc.) as means to the end of the d) even if adult cells can be used for some alleviation of suffering; research purposes, the stem cells cells of the c) to permit stem-cell research on embryos embryo are uniquely suited for other  would be to permit therapeutic cloning  types of research; and so to move further down the ‘slippery e) reproductive cloning is, and will continue continue slope’ towards reproductive cloning;  to be, illegal.There is no slippery slope; d) even if reproductive cloning continues to be f) it will be many years before scientists are illegal in this country, the knowledge gleaned gleaned able to make adult stem cells behave like from therapeutic cloning could be exported embryonic stem cells. Until this can be and used elsewhere for such purposes; achieved, embryo stem cells provide provide the e) such research is not necessary because only means of alleviating suffering.  the benefits to be derived from it can potentially be achieved by other means Some of these arguments are forward(specifically by using adult stem cells). looking (they consider the consequences of permitting such research), research), others are The arguments for extending the purposes backward-looking (they consider the for which HFEA HFEA might grant licences licences are, in intentions of those who do the research). brief,f, tha brie that: t: Others are based on the belief that certain a) it is wrong to allow suffering to continue acts should never be permitted whatever  when it might be alleviated;  their consequences, consequences, and whatever whatever the b) it is unprincipled to permit research on intentions with which they are carried out. embryos for some purposes but not for There is no reason why you shouldn’t others; combine the different types of argument, c) the human embr yo before the ‘primitive so long as your overall position is coherent. streak’ stage (14 days after fertilization)


Giving nature’s repair helping hand process a Natural selection has enabled our  bodies to cope with the wear and tear  caused by living, living, and to repair damage. damage. Our understanding of science and its applications has increased our chances of survival. survival. For exampl example, e, we know know how to assist the natural skin healing process by keeping a wound free of infection or, or, in the case of larger  wounds, by stitching the skin together. together. More advanced technology has supplemented our natural repair  processes as demonstrated by skin grafting, or in the case of broken broken bones, the addition addition of metal pins and splints to promote repair.

Transplantation Up to now organ and tissue  transplantation have have been among  the most dramatic technological interventions in the healing process. However,, rejection by the immune However system of the recipient has been the major challenge challenge to their success. Drugs  that suppress the host’s immune system go some way  to preventing rejection reje ction,, but  they increase vulnerability to other infections. The severity of   the immune

Alexis Carrel

reaction can be minimized by improving  the genetic match between the host and the donor, donor, so that the tissue is perceived by the body as less ‘foreign’. This is why close relatives are often the best available available donors, and why identical identical  twins are ideal donors. The ultimate aim of therapeutic cloning is to enable any  patient in need of bodily repair to receive genetically identical tissue.

Stem-cell-derived tissues Stem-cell researchers might eventually  be able to establish banks of stem cells modified in such a way that they no longer carry the biochemical markers  that trigger immune responses. If so,  then it would no longer be necessar y   to use therapeutic ther apeutic cloning techniques  to overcome the problem pr oblem of rejection for tissue grafts and ultimately even organ donation. Using cloned tissue to repair the effects of a degenerative disease caused by a variant gene would be problematic because the cloned cells would carry the same genetic defect as those they were replacing. Even though they would suffer the same degenerative process, continual renewal of the tissue could slow down the deterioration.

Alexis Carrel (right) with his perfusion apparatus,  which maintained blood blood flow to a transplant transplant organ  Jean-Loup Charmet/Science Photo Li brary 

Alexis Carrel (1873–1944) was the great pioneer of the field of biotechnology which includes cloning and tissue-culture research. He carried out his earliest experiments in skin graftingg in the 1890s, and attempted graftin attempted to grow and maintain new tissue outside the body for use in grafting and transplantation. Carrel won the Nobel Prize for Physiology or Medicine in 1912 for a method of suturing blood vessels, and pioneered the treatment of  wounds by antiseptic irrigation during World World War I, but his work in tissue-grafting and organ transplantation never overcame the problem of rejection. He was the first to demonstrate that animals tolerated grafts from their own tissues, but rejected those from unrelated animals. Carrel was able to keep chicken heart cells alive for an incredible 28 years by regularly refreshing the solution they were bathed in.

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The ethics of embryonic stem-cell research Multiple sclerosis, Parkinson’s disease, leukaemia and osteoarthritis are diseases  that cause great human suffering. Surely Surely,,  therefore, we are mor ally required to alleviate this suffering by any means available to us. Or are we? Should we really be prepared  to do anything  to  to alleviate human suffering? If we think we we should, then we are saying

“Should we be prepared to do anything to alleviate human suffering?”

 that this end – the alleviation of human suffering – will always  justify the means, whatever  the  the means. If this is right it means  that so long as good will eventually come of our actions, actions, it does not matter matter what  these 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 genetic mutation ensuring that his body contains a substance that, when taken by someone with any of the diseases mentioned above, cures them immediately and forever.There’s only one problem problem:: in order to ‘harvest’ this substance, subst ance, James must must be killed. killed. Should we kill James to alleviate this suffering? Or would it be wrong to kill James despite  the fact that it would enable us to alleviate  this suffering? This story is wildly implausi implausible, ble, of course, but it is designed only to stimulate thinking about whether we really do believe that we should do anything at all if doing it will alleviate human suffering.

“The philosopher Kant argued that it is always morally wrong to use another person simply as a means to our own ends” There are many people who think that an individual’s right to life overrides any  good we might otherwise do by killing  them.The  them. The philosopher Kant argued that it is always morally wrong to use another  person simply as a means to our own ends. Kant would certainly disapprove of killing  James in order to alleviate the suffering of others.


LabNotes new biology and society The Wellcome Trust

“A Utilitarian would argue that we should do whatever will produce the greatest happiness of the greatest number” A Utilitarian, Utilitarian, howe however ver,, would argue that that we should do whatever will produce the greatest happiness of the greatest number. On the surface surface of of it, theref therefore, ore, a Utilitarian Utilitarian would approve of killing James because in killing him we would be bringing about the greatest happiness of the greatest number. Those who believe that the use of spare embryos, or the creation creation of new embryos, embryos,  to obtain stem cells is morally wrong believe, believ e, like Kant, Kant, that even even the alleviation alleviation of human suffering is not a good enough reason to override override others’ right to life. These people believe that a human embryo, howe however ver it was created, created, has the the same moral status as a human being with a right to life that it is not morally permissible  to violate for any reason at all. Those who believe that the use of embryonic stem cells is morally acceptable, acceptable, on the other  hand, believe either that the human human embryo does not have the same moral status as a human, with an unquestionable right to life, or that its right to life life can be overridden for the greater good. It might seem that it is dangerous to believe that our right to life can be overridden for the sake of a greater good. Such a belief might lead to the idea that anyone can be sacrificed so long as someone can argue that it was for the greater good. Usually Usual ly,, though though,, those who believe believe that using spare or created embryos to obtain stem cells is morally acceptable argue for it on the grounds that human embryos do


not have a right to life because they have not yet developed to the stage where they  have hav e acquired acquired this right. Such embryos, embryos, they  argue, are not yet yet worthy of the the moral respect we undoubtedly accord to human beings at a later stage of development.  We cannot deprive someone of a right

“Embryos,, som “Embryos somee argue, argu e, ar aree not yet yet worthy of the moral respect we accord to human beings at a later stage of  development”

 they do not (yet) have, so there can ca n be no moral objection to experimenting on these embryos. Such claims are appealing. After all,  the embr yos used for research purposes are merely clusters of cells with no organs or nervous system.They neither look nor act like human beings.They are not capable capabl e of indepe independent ndent existence, existence, they  cannot make make choices, feel fear fear, pain or pleasure, pleasure, nor are they conscious. conscious. Surely to accord to this cluster of cells  the right to life is to take the idea of the right to life to extremes? On the other other hand, if it is the lack of all  these proper ties that prevents these cells from having a right to life, then anyone who is in a persistent vegetative state would also have no right to life. To one who believes that a human being, at every stage of deve developmen lopmentt and however damaged, has the right to life life this  too would be unacceptable.

The question of whether the use of  embryonic stem cells or therapeutic cloning is morally permissible is not solved by  pointing to the fact that these techniques will alleviate human suffering because that suggests that anything that alleviates human suffering is morally and ethically permissible. Nor is it solved by appeal to the fact that every human being has a right to life because it is neither obvious that the embryo has a right to life, life, nor that our our right  to life cannot be overridden for the sake of  a greater good. Questions regarding what is morally  permissible are clearly complex and not easily answered.

Christopher Reeve: Reeve: From Superman to spokesman spokesman The actor Christopher Reeve, famous Christopher Reeve, for playing the title role in the 1978 film Superman and its sequels, sequels, was paralysed paralysed from the neck down when his spine was

the all-important gaps. gaps. In 1996 Reeve Reeve and philanthropist Joan Irvine Smith established a research centre in the College of  Medicine at the University of California,

injured in a horse riding accident in May 1995. He has since become an ardent ardent supporter and fund-raiser for researc research h into medical technologies of repair, showing great courage in defying the crippling effects of his injuries and awesomee resolution in expressing the awesom hope that he may one day walk again. Many people involved in accidents suffer paralysis as a result of severed neural connections, that prevent prevent signals from the brain getting through to the limbs and may impair the function of other organs. Stem-cell research research is one field field of  research researc h offering the possibility of bridging

Irvine.The Christopher Reeve Paralysis Foundation has issued a position statement supporting research on human pluripotent stem cells.

Left: Rex Features Features Right: Kobal Collections Collections

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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 1990 HFE Act.The vote split the House as MPs had to grapple with difficult moral and ethical questions before they made their vote.Two 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 of  embryonic stem (ES) cells in research .

Anne Begg MP was born in 1955 in Scotland and joined thee Lab th Labour our Party Party in 1983 1983.. She inherited the genetic condition Gaucher’s disease meaning Gaucher’s that she uses a wheelchair. Her political poli tical interests include broadcastin broa dcasting, g, genetic research, poverty and the oil industry. She voted in favour  of  changes to the 1990 Act.

interests include agriculture, education and healthcare. She is Vice-Chairman of the All-Party Parliamentary Pro-Life Group. She voted against changes to the 1990 Act.

1.Are you in favour of the amendments that were made to the 1990 Human Fertilisation Fertilisation and Embryology Act, allow allowing ing human embryonic stem cells to be used in

2.When in your view does life begin and how did this influence your views on the use of ES cells in research?

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

AB: I believe life does not truly begin until

AB: I think the main ethical issue lies in

research resear ch and for therapeutic cloning?

a fetus is able to sustain life outside the mother’ss body. Howev mother’ However er,, I am happy that the HFEA places a limit of 14 days on an embryo used in researc research. h.

the answer to the question question as to when life life begins. I argued in my House of Commons Commons speech that anyone who already supported the use of embryos for research into such things as contraception, contraception, or is in support of  abortion, should also support support the use of  embryonic stem cells in research into serious diseases. I found that most of those those who were arguing against the use of human embryos in stem-cell research were the same people who would argue against abortion and against the use of embryos at any stage of the development in any research.

AB:Yes. I spoke in the debate in favour AB:Y of changing regulations. AW: No. I was opposed to the Human Fertilisation and Embryology (HFE) Act 1990 in so far as it allowed for the creation, manipulation and destruction of early human life. The 2001 amendments merely extend the purposes of research under the HFE Act to include, amongst other things, ‘increasing knowledge about the developm development ent of embryos’.The amendments for the first time allow pure research on embryos without reference to any clinical goals. This makes a mockery of the so-called ‘special status’ of the human embryo.


Ann Winterton MP was born in 1941 and was elected as a conservative MP in 1983. 1983. Her political political

LabNotes new biology and society The Wellcome Trust

AW: Life begins at at conception, the moment of the fusion of the human gametes (male sperm and female egg).This new human life, which comes into into existence with the formation of the one-cell zygote, has an inbuiltt capa inbuil capacity city to initia initiate, te, susta sustain, in, contr control ol and direct its own development. As human life begins at conception and the use of ES cells in research necessarily involvess the destruction of human embryos, involve I am completely opposed to such research regardlesss of the scientific and medical regardles benefits such resear research ch may bring.

AW: a) The primary ethical ethical issue is that that the use of ES cells in research involves destructive research on human embryos.These human embryos are early human beings and the amendments to the HFE Act introduced in 2001 authorize their


destruction on a far larger scale than ever before. Such research is wholly unethical. b) If the embryonic stem cells used in research are created via cloning techniques, as the 2001 amendments to the HFE Act purport to allow, this represents repres ents the practice of asexual reproduction for the first time in human history.. We should not underestimate history the threat this poses to marriage, procreation and the nature of the family. c) The use of ES cells in resear research ch carries serious and unpredictable medical risks. It is unethical to expose patients to these serious risks.

stem-cell research research as opposed to using those left over from fertility treatment. However Howev er,, I believe that it is even more important to allow embryos to be created through cell nuclear replacement because it is through this method the greatest potential lies.Where stem cells created through cell nuclear transplant from the recipient’s own cells are used, the chances of rejection rejection are are lessened. lessened. It is this cloning cloning technique which I believe will result in the greatest medical advances and will have the greatest clinical application.

4. How did you you weigh these ethical ethical issues against the potential benefits to human health when reaching your  decision about the use of ES cells in research?

in recognition of their inherent dignity as early human beings. I have always been completely opposed to the creation of ‘spare’ embryos in the course of infertility treatment such as IVF. The reason why such large numbers of  ‘spare’ embryos are created is because the success rate of treatments like IVF remains so poor (according to the HFEA Annual Report 2000 the live birth rate was 18.2%). Therefore it is perceived that there is a need to maximize the number of embryos created to maximize the chances of the treatment being successful. The Utilitarian argument that these ‘spare’ embryos should be used for destructive research perhaps in preference

AB: I have always thought that the potential benefits to human health far outweigh any moral or ethical considerations with regard to the use of embryonic stem cells in research. resear ch. I believe such research research has greater potential than say organ transplantation and may in fact be the key to finally finding a cure for some of the worst degenerative conditions that at present debilitate so many people. Howev However er,, I also believe believe such research should be subject to tight and stringent controls. AW: My ethical analysis is guided by traditional medical ethics which requires that one must establish the moral integrity of a course of research independently of its potential benefits. benefits. Certainly Certainly,, one may weigh weigh the benefits of a course of treatment against the 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 view,, an ethical difference between creating human embryos specifically for stem-cell research and using embryos left over  from fertility treatment?

AB: There is an ethical difference between AB:There creating human embryos specifically for

AW: In essence, essence, no. All embryo embryos, s, howe however ver created, are entitled to the utmost utmost respect

to embryos created specifically for destructive research research fails to recognize that the humanity of embryos entitles them to a minimum human respect, respect, despite the clear differences between between human embryos embr yos and older human beings. 6. Do you have ethical concerns over the use of fetal stem cells for  research, resea rch, such as those obtained following abortions?

AB: I do have some ethical concerns about the use of fetal stem cells but those concerns are predominantly in the area of informed consent by the person who is providing the fetus. AW: W:Yes Yes I do.Where these cells have been obtained as a result of the deliberate destruction of human life through abortion

then the use of such cells is wholly unethical. Furthermore, there is the potential problem problem that clinicians, in an attempt to obtain these fetal cells, could encourage or provide provide incentives to pregnant women contemplating abortion to proceed with their abortion. Women would be vulnerable to psychological and financial exploitation. In any event, adult stem-cell research research currently shows more clinical promise than either embryonic or fetal stem-cell research. Adult stem-cell research combines scientific excellence with best ethical practice and is a viable alternative that should be pursued in preference to all other forms of stemcell research. 7. Do you feel that that there is is a risk that the technology employed when obtaining stem cells from embryos created using cloning methods could lead the way to human reproductive cloning, in spite of the fact that at present most countries have in place legislation to prevent it?

AB: It may be that somewher somewheree in the world, an unethical scientist will try to clone a human being. Howev However er,, I do not believe believe that they will be successful because they will be operating, oper ating, in most cases, cases, outsi outside de the law and outside the mainstream scientific community. AW: W:Again, Again, yes, I do.The UK UK Gover Government nment has sought to make a clear distinction between betwe en so-ca so-called lled ‘therapeutic ‘therapeutic’’ (which should more accurately be termed ‘experimental’) cloning and ‘reproductive’ ‘reproductive’ cloning and insists that the licensing of  experimental cloning will not lead to reproductive cloning. However Howev er,, the terms ‘therapeutic’ and ‘reproductive’ ‘repro ductive’ draw neither an ethical nor a scientific distinction.They refer simply to the reasons for which a cloned embryo is created. In practical terms they they are one and the same process.The techniques that would be developed to allow cell nuclear replacement to result in a healthy, healthy, dividing human embryo would be published in international journals and could then be used by ‘rogue’ scientists anywhere in the world to produce a cloned baby.

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Adam Nash:The right cord In Colorado, Colorado, USA, Molly Nash was born with Fanconi’ Fanconi’ss anaemia, a gene-related bone marrow marrow disease that threatened her with early death. death. Molly’ Molly’ss parents, Jack and Lisa, took advantage of IVF techniques techniques and genetic screening to make sure that their second child,Adam, would not have the same disease. They took further advantage of the opportunity to select an embryo by choosing one whose tissues matched Molly’s, s, so that stem cells recovered from from Adam’s umbilical cord might be used in treating Molly’s condition, thus increasing her chances of survival considerably. Adam was born in October 2000 amid debate as to

Writers: Brian Stableford, Peter Finegold, Marianne Talbot

whether it was ethical to select an embryo for the benefits it can give, especially when that individual individual cannot give consent to being used in this way way.. Concerns were also raised over the number of embryos that were produced before a suitable match was found – over 100 embryos were produced in total.

Dr Beattie Ms Pauline Sarah Ginns Ms Nan Davies Mr Dean Madden Professor Richard Gardner 

Editor: Fern Maybee Editorial assistants: Lucy Moore, Kathryn Merritt Student activity design: Marianne Talbot Picture research: Anne-Marie Margetson  Wellcome ellcome Trust Publishing Publishing Department Design: W

Editorial advisory board: Ms Victoria Lezemore

Next issue: Ageing Top: Molly Nash Bottom:: Adam Nash Bottom


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