Cloning and Stem Cell Research

Developments in Biotechnology which could lead to new ways of treating some serious diseases but which raise ethical issues.

Some questions to consider. What is IBAC and what does it do? The Independent Biotechnology Advisory Council (IBAC) was set up by the Government in May 1999. Our main role is to help New Zealanders explore and consider issues in biotechnology. We do this by providing information about biotechnology and seeking people’s views. This information booklet is one way we are doing this. We value our independence highly. From time to time, we make recommendations to the Government on some aspects of biotechnology.

We believe that groups with different opinions can learn from one another. Part of our role is to facilitate this learning through a process of dialogue. Our approach recognises that the same facts can have very different meanings for different people. We hope to build mutual understanding and search for ways forward that benefit New Zealand.

There is a vast amount of information about biotechnology. We make this information available to the public so that well-informed discussion can proceed about issues of concern to New Zealanders. Many other countries are also grappling with biotechnology issues. We can learn from their experience, but decisions made in other countries will not necessarily suit our needs. New Zealanders need to make their own choices.

We are providing you with information about cloning and stem cell research because the Government is preparing to legislate in this area and the technology raises ethical issues that need to be discussed.

What is biotechnology? Biotechnology is a set of scientific tools which uses living things to solve problems and make products. It covers many kinds of technology. Some, like using yeasts for brewing, have been around for centuries. Others, like genetic testing, are very recent. Cloning and stem cell research form another branch of biotechnology – the subject of this booklet.

This booklet was published by:

IBAC

PO Box 530

Wellington.

Email: [email protected]

Phone: 0800 504 222 (to leave a message)

Website: www.ibac.org.nz Contents Introduction: Cloning and stem cell research...... 4

Bringing you more information about cloning...... 4

What are stem cells?...... 4

Potential medical benefits from stem cell research...... 4

How stem cells might be used in medical research...... 4

The sources of stem cells...... 5

Early embryos...... 5

Stem cells from cloned embryos...... 6

Using cloning to produce an embryo...... 7

‘Spare’ embryos...... 8

Foetuses from pregnancy terminations...... 8

Cord blood...... 9

Adults...... 9

Research possibilities...... 10

General possibilities...... 10

Specific possibilities...... 10

Ethical and legal issues surrounding cloning and stem cell research...... 11

How laws reflect divided opinions in other countries...... 11

The situation in New Zealand...... 11

Controlling cloning and stem cell research...... 12

The need for controls...... 12

Use of human embryos or other human tissue: controls in New Zealand.....12

Research on human embryos: controls in other countries...... 12

Should New Zealand have controls on cloning and stem cell research?...... 13

Why have no controls been developed in New Zealand?...... 13

Moves to introduce controls in New Zealand...... 13

An opportunity to get it right...... 13 What kinds of controls are most useful?...... 14

Unforeseen prohibitions...... 14

General prohibitions...... 14

Inconsistency...... 15

Appendix 1: Stem cell technology – a concise history...... 16 Introduction: Cloning and stem cell research When people think about cloning they usually think about copying complete human beings or animals like Dolly the sheep. Many people have strong feelings about the rights and wrongs of this kind of cloning.

But cloning is also used for purposes other than making exact copies of animals or people. The word ‘cloning’ simply means copying.

Individual cells of plants, animals and human beings are copied every day in research and clinical laboratories. For example, it is often part of testing used to diagnose people’s illnesses.

Bringing you more information about cloning This booklet is about the use of cloning in a new branch of research using embryonic stem cells. Some of the techniques used in this kind of cloning for medical research are similar to the technology that might be used to clone complete people – we will explain the similarities and differences.

In New Zealand there is currently no legislation controlling the use of embryos for stem cell research. New legislation covering these issues is currently being considered by Parliament. IBAC is presenting New Zealanders with material on the subject so that they better understand both the technology and the issues it raises.

What are stem cells? Cells which have the ability to continuously divide and develop into various kinds of tissue are called stem cells. This ability to grow into different kinds of healthy tissue makes stem cells especially interesting in medical research.

Potential medical benefits from stem cell research Stem cell technology is a new but rapidly expanding field. Researchers are hoping that stem cells can be used to repair diseased or damaged tissue in patients. This offers an alternative to:

• transplanting tissue from living or dead people, or

• gene therapy (another new technology in the very early stages of development).

There are potential medical benefits in using stem cells, but there are also ethical concerns that have to be faced before we can develop this technology further. How stem cells might be used in medical research Research with stem cells will not lead straight to medical benefits such as a new cure for a disease or condition. First some ‘basic’ work has to be done to understand more about stem cells. For example, these are some of the things stem cells could be used in research to find out:

• whether human stem cells can be multiplied for use in transplantation

• whether the cells, when multiplied, are damaged in any way

• whether their multiplication can be controlled to avoid health risks to recipients

• what leads cells to develop into specific kinds of tissue

• how cells multiply – this might help us understand and combat cancer, which happens when cells divide in an uncontrolled way to form tumours.

The sources of stem cells Stem cells can be obtained from early embryos, foetuses from pregnancy terminations, umbilical cord blood, and adult tissues. The particular ethical issues needing discussion in New Zealand arise from the use of embryos as a source of stem cells. For this reason this section provides more detail about early embryos as a source of stem cells than about other sources of stem cells.

Early embryos Each human being develops from a single cell made by a sperm fertilising an egg. The more than 200 kinds of tissue that make up the human body develop from that cell.

The early embryo, sometimes called the pre-embryo, develops from that cell over a 14-day period. In the right circumstances it will develop into at least one embryo, then a foetus, and enter the world as a newborn baby. Early embryo development:

The first cell divides into two, four, eight cells, and so on until the fourteenth day when the ‘primitive streak’ appears. After that moment the early embryo cannot become more than one child. Within the first fourteen days it can split and develop into more than one embryo. This is how identical twins are created.

At the moment the only source of stem cells that can grow into all types of tissue is from early embryos, up to 14 days old. There are two possible sources for these:

1. Embryos remaining after infertility treatments.

2. Embryos created for use in research. Separation of stem cells from an embryo:

Stem cells from cloned embryos Organ transplants in humans have been successfully carried out for decades, and have saved countless lives. But it is not a risk-free or easy process.

The human body fights against alien tissue and rejects it. This is the main problem when cells, tissue and organs are transplanted from one person to another. Medication has to be used to stop transplanted tissue from being rejected, but this can have side effects that cause other problems.

Using donor cells that are genetically the same as those of the recipient is much more effective.

Cells which are sourced through cloning early embryos have nuclear DNA that is genetically identical to the patient. Using cloning to produce an embryo There are two ways stem cells which have nuclear material identical to that of a patient can be produced using early embryos. Both procedures involve cloning to produce an embryo.

1. Removing the nucleus from a fertilised human egg (e.g. a ‘spare’ embryo) and replacing it with the nucleus of a body cell from the patient. This produces an early embryo in which the nuclear DNA is genetically identical to that of the patient.

2. The nucleus of a cell from the patient is transferred into an unfertilised human egg from which the nucleus has been removed. This also produces an early embryo in which the nuclear DNA is genetically identical to that of the patient.

This embryo could provide stem cells that are compatible with the patient and could form the basis for new tissue or a new organ.

Two methods of creating a cloned embryo:

Questions to consider: • Do you think it is acceptable to use early embryos to provide stem cells?

• Do early embryos have rights? • Is it acceptable to create an embryo by cloning in order to provide stem cells to be used for medical research or treatment?

‘Spare’ embryos There are many stored embryos in countries where infertility treatments are offered, including New Zealand. If they are not used they are destroyed or allowed to perish.

On the other hand, there is a shortage of unfertilised eggs available to infertility clinics. There are also some risks involved in obtaining unfertilised eggs from donors.

Because of these factors, researchers prefer the first option (using ‘spare’ embryos). However, this method destroys one embryo to create another embryo, which is in turn destroyed by the removal of stem cells.

Question to consider: • Is it acceptable to use early embryos remaining after fertility treatment, which would otherwise perish, to provide stem cells for research?

Foetuses from pregnancy terminations Some cells in the foetus have the potential to multiply themselves and to change into various kinds of tissue. They are also stem cells, but the range of tissues they can grow into is more limited than cells from early embryos. Their ability to renew themselves is also more limited. However, some foetal tissues do not trigger rejection problems in the recipient.

But even the more limited power of these cells to multiply and transform can still be useful. If such cells could be multiplied in the laboratory, then less foetal tissue would needed for treating patients.

Foetuses can also provide cells which would have become either sperm or eggs if the foetus had grown into adulthood. However, animal studies have shown that it is more difficult to produce normal tissues from these cells.

It is harder to collect stem cells from foetuses than from early embryos.

Question to consider: • Is it acceptable to use stem cells from foetuses for medical research or treatment? Cord blood Stem cells can be extracted from the blood in the umbilical cord after the birth of a child. Collection of these cells presents some practical difficulties. The cells have similar limitations to those removed from foetuses.

Adults Even adults can provide some stem cells, which have limited powers of renewal and change. For example, bone marrow cells can produce all the different types of blood cells and recent research with animals indicates that they may also be able to rebuild damaged tissue.

This and other recent research suggests that adult stem cells are more versatile than previously thought. Researchers are trying to discover what determines that a cell is of a certain kind, for example, a skin cell. If this process could be understood and mastered, then it might become unnecessary to use stem cells from early embryos.

This procedure might be possible in the future, but it would delay current progress in stem cell research if it were the only line of research.

Question to consider: • Is it ethical to delay research using embryonic stem cells until it is known whether adult stem cells are as useful?

Types of human stem cells and where they can be found:

Stem cell type Description Examples

Totipotent stem cells Each cell could potentially All of the cells in a human develop into a new person. embryo in the first few days. Pluripotent stem cells Cells that can develop into Some of the cells in the any of the over 200 blastocyst stage of the early different cell types found in embryo between 5 and 14 the human body. days. Multipotent stem cells These are cells that are Foetal tissue, cord blood already differentiated, but and adult bone marrow which can give rise to a cells. limited number of other cell or tissue types. Research possibilities Many things can damage tissues or organs in the body. They include:

• degenerative diseases such as Parkinson’s disease

• inherited diseases such as cystic fibrosis

• cancer

• disabling events like strokes and accidents.

There are limits to what can be done for such patients at the moment. Therapy involving the use of stem cells might provide new treatment possibilities in many of these areas.

Stem cell technology offers a number of possibilities:

General possibilities • Healthy cells capable of growing into new tissue to replace damaged tissue or organs could be introduced into the body using stem cell technology. This is likely to be safer and more successful than other tissue repair techniques currently being investigated.

• Growing tissues which are not likely to be rejected by recipients would make transplantation medicine much more successful. It would also avoid the need for powerful drugs which suppress rejection but have serious possible side effects such as cancer and reduced resistance to infections.

• Being able to grow tissue using stem cell technology could overcome the inability to treat many patients and the delays faced by patients now because of shortages of donated healthy tissue.

Specific possibilities Stem cell technology might enable us to rebuild all the types of tissue, including cartilage and muscle. Treatments based on stem cell technology could target:

• inherited conditions such as cystic fibrosis (the only treatment currently available is whole- organ transplants using donated organs)

• degenerative conditions involving damaged brain cells, e.g. Parkinson’s disease, Alzheimer’s disease

• nerve cell damage caused by stroke

• diabetes, by restoring insulin-secreting cells • multiple sclerosis, by developing missing neural glial cells

• organ failure, by growing new tissue

• heart disease, with new heart cells which will synchronise with the recipient’s heartbeat

• burns, by growing new skin

• leukaemia – compatible cells would avoid the problems of graft/host disease, a serious risk in current treatment.

Ethical and legal issues surrounding cloning and stem cell research None of the therapies mentioned can be developed without a great deal of research and this depends on adequate supplies of stem cells. At present, early embryos are the best source of suitable cells. But creating and using early embryos as a source of stem cells raises ethical problems. This is because of the range of views people have about the status of the human embryo.

On the one hand are people who see the early embryo as having the same rights to protection as they have. On the other hand are those who see the early embryo as simply a collection of cells with no special rights. There are many shades of opinion between these positions.

How laws reflect divided opinions in other countries Most countries have legislation to control human embryo research have recognised that opinions on the issues involved are divided. The resulting laws tend to take a middle road by offering certain protections to human embryos but allowing them to be created by in vitro fertilisation.

In some countries these embryos can only be used for treating infertile couples and the unused embryos are eventually destroyed. In other countries the spare embryos are made available for research which is subject to tight controls.

The situation in New Zealand In New Zealand there is no regulation in this area but opinions are also divided. Some genetic screening research on early human embryos is proceeding here with the approval of the National Ethics Committee on Assisted Human Reproduction (NECAHR). There is no stem cell research on human embryos being carried out in New Zealand at present.

Maori perceptions have been taken into account for some aspects of assisted reproduction in New Zealand. Whakapapa, the inherited and traceable common history which establishes mana and identity, would be threatened by the use of anonymous sperm or eggs. Provisions are made to avoid anonymity of donor when requested.

In stem cell technology, no practice is anticipated which would threaten identity by producing inherited traits. Nonetheless, there may be a variety of views on cloning and stem cell research held by Maori and other cultural and religious groups in New Zealand.

Issues include:

• ethical objections to the use of certain technologies

• a demand for power of veto by specific groups

• an examination of research proposals by specific groups on a case-by-case basis.

For New Zealanders it is important that all views are discussed before any laws about uses of embryos are put in place.

Questions to consider: • Do the potential benefits from using early embryos in research justify their use?

• Does such use of embryos undermine respect for human life?

Controlling cloning and stem cell research

The need for controls One response to these ethical issues would be to introduce controls over stem cell research. Types of controls can vary. For example, there can be:

• very comprehensive laws with very specific controls over many types of activity

• more generalised laws which define general outcomes and provide a framework for decision- making on specific cases

• no legal controls, but professional guidelines for groups such as doctors and medical researchers.

Use of human embryos or other human tissue: controls in New Zealand A system of ethics committees in New Zealand examines research proposals put before them involving human participants. There are no laws governing research on human embryos. Using tissue from foetuses is not against the law as long as it is neither an ‘indecent nor improper interference’. Whether the extraction of cells from the foetus would be ‘indecent’ or ‘improper’ has not been tested in the courts. Other types of tissues are harvested without legal challenge. The only possible limit would be the need for the consent of the mother. Similarly, body parts or tissues from adults – living or dead – may be taken given that proper consent procedures are followed.

Research on human embryos: controls in other countries In most developed countries there are rules governing research which destroys human embryos, ranging from a complete ban to various limits on:

• the purposes of the research

• the maximum age of the early embryos used

• the production of embryos for research

• the production and use of cloned embryos

In most countries where there are controls on the use of human embryos there is a ban on cloning human beings i.e. producing children who are genetic copies of other people.

Should New Zealand have controls on cloning and stem cell research? We might feel that the issues are too important to be left in the hands of the medical researchers – that because these issues could affect so many people, these matters should be controlled through the democratic process.

This is the view taken by most countries which have controls on human embryo research.

On the other hand, we might feel these matters are best left to the medical researchers who have expertise in the relevant area.

Why have no controls been developed in New Zealand? Stem cell research is a very recent development (see Appendix 1). So far only the United Kingdom has devised laws or regulations specifically for this activity. Most of the countries which have controls that govern cloning and stem cell research originally designed those controls for other purposes. They are usually found in laws governing the activities of researchers and doctors involved in assisted human reproduction (e.g. techniques such as in vitro fertilisation).

Because the techniques of assisted reproduction have involved research on human embryos, countries have tried to reflect their citizens’ views in the laws which govern researchers’ activities.

Many of the discoveries made in the process of this research have been imported into practice in New Zealand. However, because the original research work was performed elsewhere, there was less pressure to introduce controls here. By default, therefore, research on human embryos now proceeds in New Zealand without any specific legal controls. Moves to introduce controls in New Zealand The practice of assisted reproduction raises ethical issues such as the rights of the child and of the parents. In New Zealand these issues led to proposed controls in the form of two Bills before Parliament:

• The Human Assisted Reproductive Technology Bill (1996)

• The Assisted Human Reproduction Bill (1998)

These Bills were drafted before stem cell research developed. In May 2001 the Government announced that new legislation would be drafted, which would encompass the recent developments in stem cell technology and cloning and issues raised in the earlier Bills.

An opportunity to get it right The delay in introducing the earlier 1996 and 1998 Bills offers New Zealanders an opportunity to address stem cell research and other matters to do with human embryos.

Some countries with laws governing assisted reproduction that were devised before the development of stem cell research find those laws inadequate for dealing with stem cell research.

New Zealand can keep this new development of stem cell technology in mind with the development of legislation covering assisted human reproduction.

What kinds of controls are the most useful? We could adopt the view that no laws are required and that control is best left in the hands of the professional groups of researchers and clinicians. They would produce guidelines to cover the kinds of research which would be approved. A few countries have adopted this approach.

If on the other hand we develop laws to directly control cloning and stem cell research then we should avoid:

• unforeseen prohibitions

• general prohibitions

• inconsistency.

Unforeseen prohibitions In some countries, where the laws governing human embryo research were made some years ago, cloning human embryos and using embryos for research is banned. Stem cell research was not envisaged when the ban was made.

The result is that this type of research has been ruled out unintentionally. Stem cell researchers in such countries can only overcome these prohibitions by: • using stem cells collected from early embryos in other countries where research on embryos is allowed

• restricting their activities to the use of foetal, cord blood or adult cells.

Questions to consider: • How can we avoid the problems of unforeseen prohibitions in New Zealand?

• If the use of embryos for research is banned in New Zealand, should researchers be allowed to use embryos from other countries?

General prohibitions Laws which take the form of general prohibitions can be inflexible and do not accommodate rapid developments in either public opinion or areas of science. General prohibitions are sometimes made to ensure a ban is placed on something that a society feels very strongly about.

The problem is that specific activities such as cloning are hard to deal with in isolation. For example, many people would like to see a ban on commercialising human embryos or a ban on cloning of individual human beings – creating a new living person who is a genetic copy of its ‘parent’. But if we ban cloning altogether we could also be banning the cloning of embryos that is part of stem cell research – a branch of medicine that is not trying to create cloned people, but to seek new treatments for diseases.

If we make laws to prohibit certain activities, our challenge is to make sure that we do not inadvertently restrict other activities that we might want to continue or consider separately. One solution could be a mix of direct controls and a more flexible regulatory framework.

Question to consider: • How can we provide controls which are flexible enough to take into account technological developments in the future?

Inconsistency Laws to control stem cell research would need to be consistent with existing legislation which governs research and medical practice in New Zealand. The welfare of the foetus is already affected in several areas of law and practice. For example:

• under the Contraception, Sterilisation and Abortion Act, for a restricted range of reasons, the termination of a pregnancy and the destruction of the foetus is permitted • the prescription of the ‘morning after’ pill as an emergency contraceptive measure is common place

• research carried out on genetic screening of early embryos has been approved by the National Ethics Committee on Assisted Human Reproduction (NECAHR).

The latter two activities involve the destruction of early embryos.

Any rules about the use of early embryos for health research and, eventually, therapeutic purposes, would need to be consistent with other areas of law and practice. That could involve aligning new laws with existing laws, or conversely, amending existing laws to bring them into line with new legislation governing the use of human embryos, cloning and stem cell research. APPENDIX 1

Stem cell technology: a concise history 1663 Cells were first described by Hooke

1838 Schleiden (Botanist) and Schwann (zoologist) independently state the basis of the cell theory: All living things consist of cells. All cells come from other cells.

1902 Haberlandt suggests that all living plant cells are totipotent – that each cell carries all the genetic information for the whole organism. Not shown in practice until some 50 years later.

1944 DNA is shown to be the hereditary material in living organisms.

1953 Watson and Crick discover the double-helix structure of DNA and crack the genetic code.

1969 The first gene is isolated.

1969 Patrick Steptoe and Robert Edwards announce the fertilisation of human eggs outside the body (in vitro fertilisation). 1978 saw the birth of Louise Brown, the first ‘test tube’ baby.

1985 The first transplantation of foetal neural tissue into the brains of Parkinson’s disease sufferers claimed limited success.

1988-1994 Various countries introduce laws governing treatment of human embryos: 1988 Sweden, Spain and Australia; 1990 UK and Germany; 1992 Denmark and Austria; 1994 Norway and France; two New Zealand Bills (1996 and 1998) have not yet become law.

1991-1998 In the United Kingdom alone, 763,509 in vitro embryos were created and 48,444 given for research.

1998 James Thomson published an account of the development of pluripotent embryonic stem cells from human blastocysts.

1999 US company announces successful cloning of human embryonic cells from an adult skin cell.

2000 Japan’s main science policy body, The Council for Science and Technology, draft Bill to allow stem cell research on cloned embryos.

2000 US National Institutes of Health Guidelines allow research on stem cells obtained from spare embryos. 2000 UK Government amends law to extend the regulations governing embryo research to cover stem cell research.

2000 Stem cells induced to differentiate into forerunners of several kinds of body cells.

2001 New Zealand legislates to control assisted human reproduction?