Statement of opinion on embryonic stem cell research

Swedish National Council on Medical Ethics
Date: 2002-01-17
03/2002

1. Background

Research on stem cells has recently been the subject of great attention and lively debate. Stem cells are immature cells that have the ability to divide either for self-reproduction, i.e. generation of new immature cells, or for production of daughter cells that mature into specific tissue or organs. Stem cells are capable of replacing cells and tissue that are damaged or diseased; in fully developed individuals they can be said to constitute the spare-parts material of the body. Therefore, this field of research is exceptionally promising. During the past 40 years, important knowledge about stem cells has been generated through research on animals, especially mice. Now human stem cells are increasingly in focus for the researchers.

It is hoped that stem cell research will make possible the development of new methods of treatment for serious chronic illnesses, which today are considered incurable, such as Parkinson’s disease, diabetes, and cardiovascular diseases. There is also hope for developing the capability to repair serious and handicapping tissue damage, such as spinal injuries. At the same time, stem cell research raises complex ethical issues. The debate of today centres on whether it is ethically defensible to conduct research on stem cells from fertilised eggs that are left after test-tube fertilisation (in vitro, IVF).

Ethical problems can be analysed from various points of departure. A useful approach may be to describe the ethical controversies as a conflict between different values, between different actors’ rights and obligations, or between different interests. The question whether it is ethically defensible to do research on embryonic stem cells can be described, in a simplified way, as a conflict between the short- and long-term interests of different groups. On the one hand, there is interest in new knowledge that can lead to treatment of hitherto incurable diseases. On the other hand, there is interest in safeguarding human dignity and not instrumentalising human life. A number of concrete issues are addressed by the ethical discussion:

1. Should research be done at all upon embryos and, if so, is embryonic stem cell research more controversial than other such research?

2. Should research be allowed on fertilised eggs that are surplus from IVF treatment?

3. Should it be allowed to create fertilised eggs solely for purposes of research?

4. Should one allow cell nuclear transfer? If so, under what conditions?

Before these questions can be answered, it is necessary to clarify certain scientific and legal circumstances.

2. Different types of stem cells
Stem cells can be described with regard to their potential to differentiate, to the source from which they are derived, or more specifically to the body tissue in which they are active.

2.1 Potential to differentiate

Stem cells can be distinguished according to their ability to develop into different kinds of cells. The ultimate stem cell is the fertilised egg, which has the potential to develop all the cells that are needed to generate a new individual . The fertilised egg is said to be totipotent.

One can also speak of multipotent stem cells, which can give rise to several different types of cells in a certain kind of tissue or organ. Multipotent stem cells exist in the human body from the foetal stage and, in principle, throughout life. Examples of this are blood stem cells, which can form all types of blood cells, and neural stem cells, which can develop into different types of neurons and into support cells of the nervous system. Stem cells play a crucial role in the development of tissues and organs in the growing foetus, but they gradually decrease in number and importance. In an adult individual, the stem cells serve to form new cells in a certain type of tissue, for example in the skin, intestinal walls or blood.

Stem cells with the ability to form more or less all types of cells in the body are called pluripotent. Unlike the multipotent stem cells, they do not occur naturally in the body. Instead, they belong to the very earliest stage of biological development. They cannot, however, give rise to a new individual.

2.2 Adult, foetal, and embryonic stem cells
Human stem cells can be obtained from different sources: from children or adults (adult stem cells, or body stem cells), from umbilical-cord blood and from foetal tissue (foetal stem cells), and from eggs fertilised in test-tubes (embryonic stem cells). Embryonic stem cells, as well as primordial germ cells from foetuses, are unique in being pluripotent. Other stem cells are multipotent.

Today it is thought that the human body contains some 20 different variants of stem cells. For a number of years, the blood-forming stem cells in the bone marrow of adult individuals have been used to restore the production of blood cells in patients affected by leukaemia or aplastic anaemia. Here, then, the stage of clinical treatment has been reached successfully. Early experiments are underway where a patient’s own bone-marrow stem cells are injected into heart muscle that is impaired after an infarct. The results from animal models are promising. Moreover, there are experiments with transplanting corneal and skin stem cells. Other types of adult stem cells, though, seem to be much harder to identify and isolate.

Stem cells from umbilical-cord blood have the possibility of developing into several cell types in an organ or a tissue – they are multipotent. With the help of umbilical cord blood, one can transplant stem cells in order to increase the production of blood cells, for example in leukaemia patients. Multipotent stem cells can also be obtained from foetuses. In clinical trials, patients with Parkinson’s disease have received transplants of brain tissue from aborted foetuses. The transplants have exhibited the ability to produce dopamine and have resulted in clinical improvement, in some patients for more than 10 years. This method, however, requires brain tissue from 6-8 foetuses, and is thus difficult to handle in both practical and ethical terms. It is not yet entirely clear what developmental potential is possessed by stem cells from foetal tissue and stem cells from umbilical cord blood. Stem cells produced from foetal primordial germ cells have a special position in this respect. They possess the ability to develop into many different types of tissue – that is, they are pluripotent like embryonic stem cells. To use stem cells from foetal germ cells is however a very sensitive ethical issue.

Embryonic stem cells, which are the focus of the discussion of today, are pluripotent. They can be isolated when an egg, 5-7 days after fertilisation, has developed into a bud-like accumulation of cells, called a blastocyst. At this time, the egg has been cultivated for some days in nutrient solution. The blastocyst cells are about to differentiate, so that the outer cells will develop into a placenta and foetal membranes, while the inner cells are embryonic stem cells which, at this stage of development, can mature into all types of cells in the body. However, these cells are not totipotent, that is, they cannot develop into a new individual.

In order to make use of the embryonic stem cells, the outer membrane of protein of the blastocyst is punctured, whereupon the inner cell mass with its stem cells is collected. The fertilised egg is thereby destroyed and cannot develop further, but the stem cells can be cultivated in vitro and give rise to a new stem-cell line. To be successful, the cultivation requires, in addition to nutrient solution, so-called “feeder” cells or support cells. Until now fibroblasts from animals have been used for this purpose. A stem-cell line is the designation for those stem cells that have been cultivated from one and the same fertilised egg. If the stem cells are of good quality and if they do not age, the same stem-cell line can yield virtually unlimited amounts of stem cells. Besides their broad potential for development, embryonic stem-cell lines have proved better able to survive in the laboratory than other types of stem cells.

3. Reasons for research on stem cells

Stem cells are of great interest in numerous areas of medical research:

3.1 Fundamental evolutionary biology

Stem-cell cultures can be studied in a manner that is not possible with human embryos. The basic research concerning stem cells offers unique opportunities for a deeper understanding of evolutionary biology and the process leading from embryo to human being. It can also cast light upon causes contributing to infertility and miscarriages.

3.2 Pharmacological and toxicological studies

Cultivation of specific stem-cell lines enables rapid testing of how different chemical substances influence the cells. This is an area of application that will probably emerge in the very near future, and which may decrease the use of experimental animals in early pharmacological trials.

3.3 Gene therapy

Stem cells can be utilised as vectors, i.e. bearers of genetic information in gene therapy. A problem for the research on gene therapy has been to find harmless vectors and stem cells may provide a solution here. At present, experiments are being done with gene therapy to treat diseases of the blood system. Their aim is to introduce new “healthy” genes in the blood-forming stem cells, which can then develop into all types of cells and, moreover, are able to renew themselves.

3.4 Development of transplantation tissue

There is currently a serious shortage of donors of organs and tissues for transplantation. High hopes are therefore raised for the possibility of developing specific stem cell lines into tissue to be transplanted. Damaged or dead tissue could then be repaired or replaced.

Some of the illnesses which one hopes to cure or substantially relieve are Parkinson’s disease, diabetes, cardiac and vascular diseases, multiple sclerosis, and spinal injuries that result in paralytic conditions. Animal experiments in this area are promising, but there remain several years of research before one can expect clinical treatments. A prerequisite for success is likely to be the development of methods for cultivating human stem-cell lines without any support cells from other animal species. Another central problem area will be how to prevent rejection of the transplanted tissue.

4. The need for diversity in research on stem cells
All of the above-mentioned areas of research seem important. However, the question remains, which types of stem cells do the researchers need to use in order to succeed? From an ethical viewpoint, if one can attain equivalent urgent goals of knowledge, it is preferable to use stem cells that can be acquired with no risk of human suffering or destruction of potential life. Since both foetal and embryonic stem cells have given rise to ethical questions, strong hopes have been directed toward the possibility of using adult stem cells. A further advantage is that one has the opportunity of obtaining informed consent from the person involved. The research with adult stem cells has made great progress even during the past year.

4.1 Research with adult stem cells
Adult stem cells exist in many more organs and tissues than has previously been realised. Their task is to renew and repair the body’s organs and tissues. The adult stem cells have a higher capacity to mature into different types of cells than was once believed. It has also been shown that adult stem cells can go backwards in their differentiation and be reprogrammed to give origin to another type of stem cell. According to reports of animal experiments, blood cells under certain conditions can be developed from neural stem cells, and neural stem cells from bone-narrow stem cells. Furthermore, neural stem cells have been shown to exist in the brain of a fully grown individual. This was a sensational discovery, as it challenges the previous understanding that the brain lacks an ability to repair incurred damage. Some clinical experiments are also being done with transplanting adult stem cells, such as insulin-producing cells form donors to patients with diabetes. However, rejection reactions and the need for life-long immunosuppressive medication are as yet an unsolved problem with such transplantation.

4.2 Can stem cell research be restricted to adult stem cells?
On the basis of present knowledge, adult stem cells have clear limitations. They do not possess the capacity of embryonic stem cells to mature into a great variety of tissue types – they are multipotent, but not pluripotent. Certain adult stem cells are also difficult to isolate in sufficient quantity and to keep alive in culture. There are, to be sure, well-developed techniques for isolating adult stem cells in blood-forming organs, a fact that has been useful in treating malignant blood diseases. However, it is very much harder to work with stem cells in other internal organs of the body, and their retrieval makes it necessary to expose the donor to discomfort and sometimes even to risk. For example, neural stem cells in the brain of a living person are difficult to reach without an operation that entails significant risks for the individual. The experience with stem-cell cultivation also shows that adult stem cells are harder to cultivate. They do not seem to possess the same life-length and robustness as embryonic stem cells. This has been observed in a large number of studies of adult stem cells from rats. In addition, limited experience until now indicates that the relative difficulties of cultivating adult stem cells may be more pronounced for human cells. To summarise, the developmental potential of adult stem cells, and their availability for experimental studies, appear to be considerably more limited than is the case for embryonic stem cells.

4.3 Why is research on embryonic stem cells important?
Embryonic stem cell research provides opportunities for studying basic evolutionary biology, for learning more about which properties and developmental potential the stem cells possess, and for understanding the mechanisms that guide their differentiation and survival. Such basic research has the capability of generating completely new knowledge regarding what happens in early biological development. Deeper knowledge about the development of stem cells is also an important prerequisite for the continued research with adult stem cells, such as the experiments on making adult stem cells revert to a less differentiated stage.

Embryonic stem cell research is expected to yield new insights into embryonic development and the causes of congenital diseases and early malformations. It is presumably essential for ensuring that future cell treatments – whether these involve embryonic, foetal or adult stem cells – will rest upon a sound foundation of knowledge. Detailed knowledge about the molecular basis for stem cell differentiation is a precondition for being able to guide this process in a controlled manner. With good fundamental knowledge, one should be able to radically reduce the risks of future experimental treatments, such as the risk of tumour development.

4.4 Future use of adult, foetal, or embryonic stem cells
Stem cell research finds itself in a dynamic, yet still early, stage of progress. Some areas of research are closer to application than others. Fairly imminent is the use of stem-cell lines for initial pharmacological trials, which means that one has an opportunity to directly observe how different chemical substances influence the cells. This has the good effect of decreasing the need for experimental animals. Less certain is how soon treatments of various degenerative diseases can become clinical practices. It probably lies farther in the future than is hoped by many afflicted patients and their relatives. The research on how stem cells can be made to mature into a specific tissue is at a very preliminary stage. Still unresolved are the immunological questions and problems with rejection.

Today it is impossible to foresee which contributions will be made by research on embryonic, foetal, or adult stem cells. Scientific breakthroughs are hard to predict. What remains clear is that the embryonic stem cell research at the present stage is in a position to contribute pioneering knowledge which would move the entire field of research forward and closer to clinical application. Researchers of diverse orientations are in agreement on this. They also agree that the research should be conducted on a broad front, that is, with all types of stem cells. Which type of stem cells will dominate when it is time to take the step from research to clinical practice cannot be foreseen.

5. The legal framework

In Sweden, research on fertilised human eggs is regulated by the law (1991:115) on measures with fertilised eggs from humans for purposes of research or treatment. According to the law, experiments may be done no later than the fourteenth day after fertilisation. Experiments on fertilised eggs must not have the aim of developing methods to produce genetic effects that can be inherited. A fertilised egg, which has been subjected to experiments, may not be inserted in a woman’s body, and must be destroyed at latest 14 days after fertilisation. A fertilised egg may be preserved in frozen condition for normally no more than 5 years; the time during which it has been frozen is then not counted in the 14 days allowed for experiments.

When new techniques are introduced in health and medical care, it must be possible to conduct research on them. The law (1991:115) on measures with fertilised eggs from humans for purposes of research or treatment was created primarily in order to regulate research devoted to improving the techniques for test-tube fertilisation. However, embryonic stem cell research means that the fertilised egg is used for a quite different purpose of research, namely for research devoted to developing new and effective methods of treatment for serious and currently incurable illnesses. That such opportunities would arise was unknown when the law came into being. Nonetheless, the law (1991:115) in itself does not pose any obstacles to embryonic stem cell research. According to the preparatory work (Bill 1990/1991:52), research on human embryos may also be done in order to acquire new knowledge about factors of importance for embryonic development. Aspects of embryonic stem cell research are specifically directed toward such goals of knowledge. As mentioned previously, the embryonic stem cells are collected when the fertilised egg is 5-7 days old, i.e. in the stage before the implantation phase, and thus it is not relevant to exceed the 14-day limit. Neither do the legal rules for freezing fertilised eggs constitute any problem for stem cell research. On the other hand, the law gives insufficient guidance about what can be regarded as acceptable research aims, or what principles should be applied to protect the fertilised egg. Nor does it say anything about the research being an object of ethical evaluation.

To establish a stem-cell line, the embryonic stem cells must be cultivated in the laboratory. Neither isolated stem cells, nor established stem-cell lines, are regulated by the law (1991:115) on measures with fertilised eggs from humans for purposes of research or treatment. They can, however, probably be considered to fall under the coming law on bio-banks in health and medical care etc., although the law proposal is not quite clear on this point (Bill 2001/02:44). According to the proposal, every donor of biological material shall have the right at any time to withdraw a prior consent, but “what shall be destroyed is the tissue sample that has been submitted for research, and not the result of the research” (par. 10.7, p. 44). Fertilised eggs are included in the law since they are considered to constitute a tissue sample, and the same applies to stem cells that are taken from a fertilised egg. By contrast, a stem-cell line could be regarded as a result of the research. The bill is unclear on this point, though, and it is not explicitly stated how long the donors are considered to have the possibility of withdrawing their consent with a request that the biological material be destroyed.

The Council of Europe Convention on Human Rights and Biomedicine (1997), which has been signed by Sweden, states in its Article 18 two conditions for research on embryos fertilised in test tube. The first condition is: “Where the law allows research on embryos in vitro, it shall ensure adequate protection of the embryo.” Current Swedish legislation contains certain important restrictions, but it is questionable whether these suffice to meet this condition. The second condition is: “The creation of human embryos for research purposes is prohibited.” Thus, creation of embryos to obtain material for stem cell research would explicitly violate the Council of Europe Convention. Yet today there is no explicit legal ban against this in Sweden. The lack of legal regulation emphasises the need for ethical analysis.

6. Instrumentalisation and protected value – “not just a means”

The fundamental ethical problem is the conflict between, on the one hand, research interests and the opportunity for new knowledge and new treatments of hitherto incurable illnesses, and on the other hand a requirement of respect for the human embryo, for integrity, human value and human dignity.

Should research be done at all upon a fertilised human egg? Does such research not imply that the fertilised egg is used as a means, and that human life is thereby instrumentalised? Do we risk undermining human dignity? How these questions are answered depends greatly on what moral status one attributes to a fertilised egg. When does human life begin? Both the sperm and the egg are living organisms. When their merging is completed, a new organism arises that has a potential to develop with an ever higher degree of complexity. Three different views can here be distinguished:

1. Human life begins at fertilisation, and the fertilised egg has full human value, i.e. the right to protection and an unconditional right to life.

2. The inception of human life is a process, where the fertilised egg is a life in the making, with a value to be protected. This value increases gradually during the course of development. Milestones in the early development are: implantation, when the fertilised egg, just over a week old, attaches to the placental wall; gastrulation, just over a week later, when the neurocanal is first formed; development from embryo to foetus, during the ninth week of pregnancy; and finally, the time when the foetus can survive outside the mother’s body, when the value of the foetus has become its full human value.

3. The fertilised egg has developmental potential but, in itself, no value to be protected.

Most people in Sweden can be assumed to attribute some, but not an unconditional, value to a fertilised egg and thus adopt the second view. There are, of course, also people who have a different outlook. Some take the first view and attribute to a fertilised egg, without hesitation or limitation, the same value as a fully developed child, and therefore believe that no research on fertilised eggs should be allowed. There are also those who consider a fertilised egg, and even a relatively developed foetus, to be like any other human tissue, and thus adopt the third view.

Comparatively wide room for interpretation exists within the bounds of the second view. A generally held attitude is that both the developmental potential and the degree of development influence the value to be protected. It is not obvious, however, at what point during the process a life in the making becomes an individual with full and inviolable human value. Opinions are partly divergent. Since 1985, this Council has dealt with the question in a long series of cases, and in detail most recently in a report, The beginning of life (2000, in Swedish).

One of the arguments against extending the research allowed on embryos to include research on embryonic stem cells is that it leads to instrumentalisation of human life. The concept of instrumentalisation signifies that something is systematically used as a means to achieve something else, and that this undermines the former entity’s value in itself. It becomes solely a means. If embryos are created solely for research purposes, instead of using supernumerary embryos that are left after infertility treatment, then they have been created just as a means in the service of research. According to many people, this implies a more marked instrumentalisation than if surplus embryos are used.

The Council of Europe Convention, Article 18, expresses the basic outlook that a fertilised egg is a potential life and, as such, has a certain value to be protected. The convention leaves the door open for research on embryos, but emphasises that the research must be carried out in carefully regulated forms. At the same time, it forbids the production of human fertilised eggs for use in research. The line has been drawn so that a fertilised egg will not become solely a means.

The European Group of Ethics in Science and New Technologies, and the Nordic Committee on Bioethics, in their respective statements of opinion, stress the potential utility and value of embryonic stem cell research, while they also reject the possibility of creating fertilised eggs solely for research purposes. This is in harmony with the Council of Europe Convention.

7. Embryonic stem cell research – ethically acceptable within certain bounds

During the last two years, the Council has kept itself informed about the progress in stem cell research. Since October 1999 the Council has invited leading authorities in the field to its meetings. Expert members of the Council have continuously followed the international developments in the field, regarding scientific, ethical and legal aspects. The Council was co-arranger of a symposium at the Swedish Medical Society’s national convention in 2001, with the title “May and should one do research on human embryos?” The Council has taken account of current literature and international policy documents. Individual council members and the secretariat have also had contacts with additional experts on adult, foetal and embryonic stem cells.

On the basis of this knowledge the Council considers that embryonic stem cell research has a special status for the advancement of this field of knowledge as a whole. Thus, there are persuasive scientific arguments that the research should be pursued with adult, foetal and embryonic stem cells in parallel.

The value of the new knowledge must nevertheless be weighed against the risk that embryonic stem cell research might undermine respect for human life and human dignity. A fertilised egg is a potential life; given certain preconditions, it could develop into a human being. The fertilised eggs that would be used in this context are left after test-tube fertilisation. Either they have been put aside at an early stage because of their inadequate quality, or they have been preserved frozen for a time and the couple no longer has any intention of using them because the treatment has already yielded the desired result. In neither case would the eggs develop further, since they will not be inserted in the body of the woman. If they are not used for research purposes, they will be destroyed.

Research with human adult stem cells is also not free of ethical complications. In order to isolate these, one must expose the research person to some level of discomfort or risk. It can be especially difficult and risky to isolate stem cells from the internal organs of a living human being; an example clear to us all is that of neural stem cells in the brain.

The Council also wants to stress that it would entail an ethical responsibility to refrain categorically from the possibility of conducting research on embryonic stem cells, and to decline an advancement of knowledge which could have great importance for many seriously ill people.

Consequently the Council considers, with reference to the principles of beneficence and non-maleficence, that there should be opportunities of conducting research on embryonic stem cells.

In addition, the Council wishes to point out that it would involve a kind of moral double standard to regard this research as ethically unacceptable and therefore not to allow it in Sweden, if at the same time one is prepared to utilise the results of international research in the field.

An ethical analysis and evaluation must continually take place. One precondition for considering embryonic stem cell research to be ethically defensible is that it be subject to public scrutiny and regulation. Moreover, each individual research project must undergo legally regulated ethical examination by a committee for research ethics. Such an examination must include a judgement of whether the same knowledge could be obtained by other methods. Research on embryonic stem cells can be allowed only if there are no scientifically well-founded and ethically acceptable alternatives for attaining the same goals.

Another important precondition is that the research field as a whole is subject to open and continuous ethical discussion. The fears and apprehensions expressed in the lively debate during the autumn of 2001 have not been dismissed. They should be sustained in the discussion and in the evaluation of the continued progress of knowledge.

7.1 Stem cells from embryos donated after test-tube fertilisation

Research on stem cells from supernumerary embryos that are left after infertility treatment is compatible with current Swedish legislation, as well as with the Council of Europe Convention, provided that both of the donors have given their consent.

In the opinion of this Council, there are several ethically relevant differences between (a) the creation of a fertilised egg solely for research and (b) the use in research of fertilised eggs that have been created for purposes of treatment. The first case would require that the woman be subjected, solely for research purposes, to a hormone treatment and an invasive measure. This is something which, with reference to the principle of due caution, there is reason to avoid if alternatives exist. In the second case, eggs are used that have been left after test-tube fertilisation. To spare the woman repeated operations, several eggs are taken out on a single occasion for IVF treatment, which leads in most instances to a certain surplus of fertilised eggs. These will not be used in the attempts to create a pregnancy in the woman, either because they are not of sufficiently high quality, or because the treatment has already given the desired result and eggs that have been frozen are surplus. Thus, the eggs lack the possibility of developing further and must be destroyed within the time limit stipulated by the law (1991:115). The choice is therefore between destroying the supernumerary fertilised eggs after carrying out research on them, or destroying them without doing research.

One can also argue that the creation of embryos for research purposes would involve an additional step toward instrumentalisation of human life. Moreover, this seems unnecessary in purely practical terms, since there is at present a good supply of embryos that have been left after treatment for involuntary childlessness.

A prerequisite for allowing the research is that both of the donors have given their consent. Information about the research should be given stepwise, both orally and in writing. The couple should receive information already in connection with the first consultation, so that there is time for reflection and for asking new questions. Renewed information must be given in connection with the possible donation. Before consent is obtained, the couple shall have received complete information about the method and purpose of stem cell research, what their possible consent entails, who is responsible for the research, and that they have the right to withdraw their participation at any time. It is an absolute requirement that both of the donors are clearly informed that the donation may result in a stem-cell line with an extensive life-length. The donors have the right to withdraw their consent, but it is not clear over what period this right extends. It is not a given fact that they shall be able to request destruction of a stem-cell line, since an established stem-cell line could be regarded as a research result rather than a tissue sample (see Bill 2001/02:44). It is essential that regulations and practice become clarified on this point, and that both of the donors receive full information about current rights and obligations.

Consent must be obtained with special care and with respect for the extremely sensitive situation in which the couple find themselves. From an ethical viewpoint, it is preferable to use, if possible, frozen fertilised eggs. The couple can then be asked after they have terminated their treatment, when it is entirely clear that they no longer need the frozen fertilised eggs. It is important that the couple do not experience that they have a relationship of dependence on, or a debt of gratitude to, the researcher. This means that the treating physician and researcher must not be the same person. Even if one distinguishes between roles and functions, the couple may be in a psychological state of dependence with regard to the clinic, and it is therefore imperative that one be sensitive to possible signs of anxiety or doubt in either of the parties. A desire not to take part must obviously be respected, even if it is expressed in a less articulate manner. These ethical considerations have still greater weight if the question concerns surplus, fresh eggs 5-7 days old. In this case, the possible donation coincides with the IVF treatment itself, and the couple are psychologically – as well as physically, for the woman – in a highly vulnerable situation.

7.2 Cell nuclear transfer

Cell nuclear transfer means that the genetic material in a cell is exchanged, by replacing the nucleus in one cell with the nucleus from another cell. What has hitherto aroused most discussion is somatic cell nuclear transfer (SCNT).

In somatic cell nuclear transfer, the nucleus from a foreign body cell is transferred to an egg whose nucleus with the genetic material has been removed. The genetically changed egg is cultivated in the laboratory. When the blastocyst stage is reached, one can collect the inner cell mass and cultivate pluripotent stem cells that are genetically identical to the individual from which the inserted cell nucleus came. The hope is that, in future treatments, this will enable the creation of stem cells and tissue which genetically match a sick patient. In this way, the problem of rejection of transplanted tissue would be solved. Somatic cell nuclear transfer has also been called therapeutic cloning. Ethically, the method is particularly sensitive, since one initially uses the same technique as in reproductive cloning. Under some conditions, the embryo that is created through the nuclear transfer could give rise to a new individual. There is no absolute biological barrier to such utilisation.

The technique of nuclear transfer is still very uncertain, and one must expect to expend a large number of eggs in order to bring about a single successful nuclear transfer. This constitutes a further ethical complication. Which women would donate these eggs? What inconveniences or risks would it entail for them? Do we have sufficient guarantees for complete protection against commercialisation? The knowledge base as a whole is still deficient, and clinical transplantations lie far in the future. Continued research may find other, and perhaps ethically less controversial, opportunities for dealing with the problem of rejection.

A possible approach could be somatic nuclear transfer to cells that cannot develop into a new individual. In October 2001, researchers in Göteborg reported having succeeded, in animal models, with nuclear transfer to embryonic stem cells. Stem cells established in cell culture are no longer totipotent, and there is thus a clear biological restriction which means that these genetically altered cells cannot be used for reproductive purposes. An established stem-cell line could then yield a virtually unlimited supply of material for experiments with somatic nuclear transfer. In animal experiments, some progress has been made, but much research remains to be done before nuclear transfer to human stem cells can be expected to become a reality.

In Great Britain a decision was made in January 2001 to allow research on human embryonic stem cells, and also to allow nuclear transfer to egg cells. According to a court ruling in November 2001, the latter decision led to a legally unclear situation, where even reproductive cloning – that is, cloning of entire human beings – must be considered permissible by British law. The court ruling has aroused dismay among both legislators and researchers. A rapid inquiry was initiated in order to supplement the law as soon as possible.

The British experience points to the importance of a satisfactory legal regulation of the field. Today there is no general ban against reproductive cloning in Sweden. This Council considers that such a ban must be introduced to Swedish law as soon as possible, and that the supplementary protocol of the Council of Europe Convention on a ban against reproductive cloning of human beings should be a starting-point.

This Council believes that there are numerous important medical-ethical and legal issues surrounding cell nuclear transfer which call for further elucidation and analysis. Cell nuclear transfer to egg cells, or to fertilised eggs, means that one produces embryos for research purposes – which, as we have seen, conflicts with the Council of Europe Convention on Human Rights and Biomedicine. Given the current state of knowledge, it is appropriate to keep open the question of cell nuclear transfer. Therefore, this Council considers that Sweden should not introduce to Swedish law any ban against production of embryos for research purposes. The area is complex and includes a number of issues, which may require different resolutions. The Council intends to carefully follow developments in the area.

7.3 Commercial aspects

Stem cell research is currently in a dynamic stage and is costly. Government authorities frequently point out the value of collaboration between industry and academic researchers. Company-financed research is predominant in Sweden. Furthermore, grants from the state do not fully cover the academic research. The Swedish Research Council finances hardly 10% of the medical research in the country. Many believe that the possibilities of public financing are insufficient and that successful research on embryonic stem cells will require support by risk capital. Companies have already been established, which include researchers from the Karolinska Institute and the Sahlgrenska University Hospital.

Academic research and industrial research are pursued under somewhat different conditions. Both categories of research are needed; they complement each other and work with different time perspectives In industry, it is natural to see expenditures on research as investments, which must yield returns within a limited period of time. The commercial interests in this field are linked to hopes for breakthroughs in stem cell research that should enable, for instance, pharmaceutical companies to earn profits on new medicines.

The advantages and drawbacks of commercialisation must be discussed in relation to the goals of the research activity. How the goals should be interpreted, specified and ranked is therefore a key issue.

Important values and goals are associated, for example, with freedom of research as well as with the possibility to develop new knowledge and new methods for curing illnesses. However, these values must be balanced against other values and goals that set limits. The latter include the respect for human dignity, equality and integrity. This implies, among other things, that human beings are ends in themselves and must not be handled solely as a means for other values. It also implies that human organs and human tissue must not be regarded merely as material.

Additionally, the goals can be specified in terms of threats, that is situations that one wants to avoid. One threat could be that undesirable commercialisation of research influences the orientation of research and resources, creating a bias toward development of patentable products and what may be profitable for the pharmaceutical companies, while other urgent needs of research are set aside. This threat is important to recognise, as is the question of who will have access to the new commercial products and be able to afford them. The last matter is a fundamental issue of justice.

A way of maintaining and strengthening the trust in research is a clear role allocation, to show which roles the different actors should play. This applies not only to researchers and industry, but also to universities, research councils, supervisory authorities, and others involved.

If the researchers own companies and have economic interests of profit in the business, potentials for conflict of interest are built into the system. Such double roles can also give grounds for suspicion of individuals and of results. Numerous examples exist of how companies that are dissatisfied with research results have tried to prevent publication. To a certain extent, Swedish stem cell researchers have participated in forming companies in order to secure the economic basis for their research. There is reason to discuss whether this might harm public trust in the activities and, if so, what forms of scrutiny might be able to counteract such a risk.

In the case of stem cell research, commercialisation may entail special ethical complications. The Swedish law on transplantation forbids the sale of biological material from a living or deceased person, or of tissue from an aborted foetus. Similar bans exist in the Council of Europe Convention. The European Group of Ethics has expressed its opposition to allowing the purchase and sale of embryos or tissue from aborted foetuses, and considers that any import or export of stem cells and their products must be done under licence from national or European authorities. Several of these documents contain rather vague formulations. There are diverse forms of conceivable barter to which they do not explicitly refer.

It is necessary to revise the Swedish law on transplantation, so that it will explicitly state that its ban against commercial handling of human biological material, also covers embryos and stem cells. A precondition for the meaningfulness of bans are that one can control whether they are obeyed or not and that they cannot be easily circumvented through other (legal) constructions.

It is also urgent to discuss the question of patents, that is, the possibility for legal protection of inventions involving embryonic stem cells. An important task is to clarify the distinction between what is to be regarded as human tissue and what, in this context, is to be regarded as a biotechnical innovation.

The Council wishes to point out the significance of a deeper analysis of these issues, and intends to return to them later. A key point of departure is that stem cell research, to the greatest possible extent, should be safeguarded from unethical commercialisation.

7.4 Concluding views

It is urgent that opportunities exist for conducting embryonic stem cell research, in parallel with research on other types of stem cells. Moreover, it is important to highlight the risk of placing excessive hopes on this promising orientation of research at the cost of other efforts. Speaking too optimistically of the future possibilities for treatment can raise an ethical complication. Seriously ill people and their relatives, as well as those citizens who have reservations of conscience about all non-reproductive handling of human embryos, must be informed that the research is long-term and that no guarantees for success can be given.

At this time, the Council has taken a position on some issues which have been central to recent debate, and which are decisive for the most immediate choices of direction for research. Other questions have been left unanswered at present. New questions will emerge. In a field of research that is seeing rapid progress, all guidelines and recommendations should be considered as provisional. If, for example, a breakthrough in research occurs with regard to adult stem cell potential for differentiation and to possibilities of controlling it, this will have a radical impact on current guidelines. The Council intends to continuously monitor developments in the field.

8. Summary

The Swedish National Council of Medical Ethics considers that there should be opportunities for conducting research on embryonic stem cells. The Council believes that under certain circumstances it can be ethically acceptable to perform research on fertilised eggs, and that embryonic stem cell research in itself is not more controversial than other research on embryos. Embryonic stem cell research has the possibility of contributing new knowledge that may become very important for future treatment of many different illnesses. There is every indication that stem cell research should be pursued on a broad front, with adult, foetal and embryonic stem cells. In this context, embryonic stem cell research can be expected to yield unique possibilities of understanding the fundamental mechanisms of biological development, which are also significant for the continued research on adult stem cells.

Therefore, the Council holds that embryonic stem cell research

· is ethically defensible on the condition that it is conducted in controlled forms and under public scrutiny, including legally regulated ethical examination of each individual project by a committee of research ethics;

· is permissible only if there are no scientifically well-founded and ethically acceptable alternatives for attaining the same goals of knowledge;

· may, after careful information to, and free informed consent from, both the woman and the man, use fertilised eggs which are left after test-tube fertilisation and which have been donated explicitly for this purpose;

· does not justify the creation of embryos, through test-tube fertilisation, solely for research purposes;

· must be subject to continued evaluation and ethical discussion, in pace with the growth of knowledge and the development of new techniques;

· must be protected from unethical commercialisation.

The Council has not, at this stage, taken a position on the issue of cell nuclear transfer. The medical-ethical and legal implications of allowing cell nuclear transfer to egg cells, or to fertilised eggs, are insufficiently elucidated at present. Consequently, the issue should remain open until the level of knowledge and understanding is adequate to provide a base for policy decision. For the time being, a ban against creation of embryos for research purposes should not be introduced to Swedish law. As a first important measure, the Council strongly recommends

· that reproductive cloning be forbidden in Swedish law.

 

 

GLOSSARYAppendix 1

adult stem cells – stem cells from a fully developed individual. Adult stem cells have a limited capacity to develop into other types of cells. They exist in many different organs and can be said to constitute the spare-parts material of the body. Adult stem cells are used in medical treatment of, for example, malignant blood diseases.

blastocyst – a 5-7 day old embryo, which is a bud-like formation of cells. The outer cells are intended to form the placenta and foetal membranes, while the inner cells develop into the actual embryo. On the fifth day after fertilisation, the blastocyst is ready to implant itself in the mucous membrane of the uterus.

cell nuclear transfer – exchange of the genetic material in a cell, by replacing the nucleus of one cell with the nucleus from another cell.

cloning – the use of somatic cell nuclear transfer to create cells, tissue, or individuals with genetic material identical to that of the individual from which the somatic cell came.

embryo – the stage of development following fertilisation. In humans, the embryo constitutes a developmental phase of up to eight weeks after fertilisation, after wchich it is considered a foetus.

embryonic stem cells – stem cells from the blastocyst stage. They are pluripotent, i.e. able to develop into all cell types in the human body.

fertilised egg – arises when an egg cell and sperm are united to form a cell with a double set of chromosomes, called a zygote.

fibroblast – a type of connective tissue cell.

implantation – the process by which the blastocyst, i.e. the fertilised egg 5-7 days old, is attached to and embedded in the mucous membrane of the uterus.

multipotent – ”capable of much”. Cells that are multipotent can develop into several different types of cells in a tissue or organ. They exist in the human body from the foetal stage and, in principle, throughout life.

pluripotent – ”capable of most”. Cells that are pluripotent can develop into all types of cells in the body, but not into a new individual. They do not exist naturally in the body, but belong to the very earliest stage of biological development.

rejection – occurs when the immune system of the body recognises foreign cells and attacks them.

reproductive cloning – a method of creating new individuals by transferring the nucleus from a body cell of an adult individual to an egg cell, thereby producing an embryo which is implanted in a uterus. This technique was used to create the sheep Dolly.

somatic cell – a cell from any part of the body, not an egg or sperm.

somatic cell nuclear transfer – a technique by which the genetic material (cell nucleus) from a foreign body cell (somatic cell) is introduced into an egg cell from which the genetic material has been removed.

stem cells – immature cells that can give rise to new immature cells by division, or to more specialised daughter cells.

stem-cell line – stem cells that are cultivated in the laboratory and have an unlimited ability to divide themselves. A stem-cell line are stem cells which originate from the same fertilised egg.

therapeutic cloning – the creation, through somatic cell nuclear transfer, of an embryo with genetic material identical to that of the individual from which the body cell came. It is hoped that this technique will make possible the creation of stem cells and tissue that match a sick patient, whereby rejection can be avoided.

totipotent – ”capable of all”. Cells that are totipotent can develop into all types of cells in the body and placenta , and thereby into a new individual.