I. Medical and Scientific Aspects
What are stem cells?
The term 'stem cells' covers a non-uniform group of cells which, at least, share the following two properties:
- Stem cells are precursor cells of highly differentiated cells.
- After the stem cells have divided, the daughter cells can be either stem cells again (capable of self-renewal) or can differentiate into specific tissue, e.g. cardiac, neuronal, skin or muscle cells.
Stem cells can be identified first in the process of early embryonic development. The zygote is a totipotent stem cell (fig. 1). It develops in the early embryonic stages and forms the basis for all human tissue that is developed at later stages through specialisation or "differentiation". The further the specialisation process of the daughter cells of a stem cell advances, the more the spectrum of their differentiation potential into various types of tissue is restricted.
Stem cells also go on to exist throughout the human life span in various types of adult human tissue, playing an important role in tissue regeneration and repair. They maintain the functionality of tissues and organs by supplying differentiated cells to replace damaged or dead cells.
The classification and identification of stem cells is not entirely consistent and, therefore, may easily lead to misunderstandings. Stem cells are classified and identified either according to their potentiality or, as is more common, according to their derivation. In everyday language, a distinction has emerged between adult and embryonic stem cells. However, from a scientific point of view it would be more accurate here to talk of tissue-specific cells instead of adult cells as opposed to stem cells which, depending on their origin, are described as
- EC cells (embryonic carcinoma cells) from embryonic tumour cells,
- EG cells (embryonic germ cells) from foetal precursor cells of gametes,
- ES cells (embryonic stem cells) from early embryonic stages (blastocysts).
The derivation of embryonic stem cells from blastocysts, during which the early embryo is destroyed, is ethically highly controversial.
The following properties of embryonic stem cells have been identified:
- In cell culture embryonic stem cells are capable of infinite division.
- Their chromosome number remains stable.
- Under suitable conditions, they are capable of developing into all types of body tissue - i.e. they are
These website pages are here to help answer questions such as:
- ‘What are stem cells?’
- ‘How are they extracted?’
- ‘What is the current state of affairs in research?’
- ‘What regulations are there regarding the research and use of stem cells?’
- How are human embryoic stem cells derived from blastocysts?
Currently, the technique most often used for the derivation of embryonic stem cells is that of in vitro fertilisation (IVF). The application of this technique has become an established procedure in reproductive medicine as a way of inducing pregnancy in cases of unwanted childlessness. During the infertility treatment, test tube embryos are directly inserted into the woman`s uterus by catheter where they can then develop into a child (fig. 2). Early embryos created in vitro can, however, also be used for the derivation of embryonic stem cell lines.
Five to six days after fertilisation,the zygote has matured into a blastocyst. It consists of an outer cell layer - the trophoblast, which forms the basis the foetal part of the placenta - and of the inner cell mass which develops into the foetus.
In order to derive stem cells (fig. 3),the trophoblast is destroyed either by using antibodies or laser technology. This renders any further development of the embryo impossible. The inner cell mass, which is now accessible, is placed and cultivated in a special culture medium in a culture dish. These cell culturing conditions allow for continued growth of cells without their further differentiation. This is the basis from which embryonic stem cells can be developed.
Up to now, there is no method capable of allowing both the derivation of embryonic stem cells and, at the same time, maintaining the integrity and developmental capacity of the embryo.
Furthermore, abroad there is intense research on educing human embryonic stem cells from previously cloned embryos. This technique did not yet succeed.
There are various imaginable ways of in vitro creation of blastocysts to be used for the derivation of embryonic stem cells. Accordingly, embryonic stem cells are subdivided into the following groups:
- ES cells generated from blastocysts created by in vitro fertilisation (IVF) (fig. 4).
- ES cells generated from blastcysts created by somatic cell nuclear transfer (SCNT) (so-called research or therapeutic cloning).
Of these two methods only the IVF has already been successfully applied in humans in order to establish embryonic stem cell lines. These cell lines mainly differ from SNCT-Stem-cells in respect of their immune tolerance. In case of transplantations involving tissue derived from IVF embryonic stem cells, severe rejection reactions are very likely, similar to those triggered by foreign tissue grafts. In case of transplantations involving tissue derived from SCNT embryonic stem cells, so-called therapeutic cloning, on the other hand, no or only minimal rejection reactions are anticipated provided the cell nucleus donor and tissue recipient would be genetically identical.
The SCNT cell nuclear transfer method could, in principle, also be used for "reproductive cloning", as has been shown in experiments with some species of mammals, where embryos from cell nuclear transfer were implanted in the uterus. The first successful experiment of this type was the creation of Dolly, the cloned sheep. However, this method is linked to high malformation and mortality rates.
- What are the goals of research involving human embryonic stem cells?
Human embryonic stem cells are of great interest both for basic research and for clinical research. Given their capacity for unlimited proliferation, it is assumed that they are an inexhaustible source for the derivation of cell and tissue substitutes. Because of their differentiation potential, they are also suitable objects of research in order to examine numerous development processes in detail.
In the context of basic research, the main focus lies on gaining insight into the molecular mechanisms of individual cell specialisation as well as on examining the organisation of cells in situ. Furthermore, the goal is an improved understanding of the development and regulation of early stem cell stages as well as of the mechanisms behind the ability to proliferate and differentiate.
In the context of clinical research there are hopes that embryonic stem cells can be used to help in the creation of tissue substitutes, in particular in the case of tissues which have only limited or no natural capacity for renewal, such as neuronal tissue. The current debate concentrates on the use of embryonic stem cells in the treatment of diseases such as Parkinson Disease and Type I Diabetes, as well as diseases of the cardiovascular system. It is also conceivable that embryonic stem cells may be genetically modified and could then be used in gene therapy, for example, to restore a destroyed immune system.
- What are the latest developments in research?
Since the derivation of the first human embryonic stem cell lines in 1998, research in this field has only made slow progress. All the same, initial results on the in vitro differentiation of human embryonic stem cells are available. Up to now, efforts to generate various cell types from human embryonic stem cells have been successfully accomplished in the case of neuronal cells, cardiac muscle cells, vascular cells, blood cells, pancreatic cells, hepatic cells and trophoblast cells. The allocation of the precursor cells to one of these groups of tissue did not generally take place on the basis of the determination of their functionality, but by determining the (surface) markers formed by the cells. In a small number of cases precursor cells derived from human embryonic stem cells were transplanted into model organisms, such as mice or chicken. There is no incidence, however, of a functional involvement of those cells in complex tissue structures. In addition, the derivation of sperm from murine embryonic stem cells has recently been described. In addition two groups of researchers recently published independently of each other techniques to reprogram human somatic cells successfully so that they show essential characteristics of embryonic stem cells.
All experiments undertaken so far fall into the realm of basic research. Neither their design nor their results currently allow for any concrete promises of clinical applications of human ES cells. This does not mean, however, that the possibility of such applications can be entirely ruled out.
Obtaining embryonic stem cells after cell nuclear transfer (so-called "cloning for research purposes" or "therapeutic cloning") has proven to be technically very difficult in humans - leaving aside the ethical and legal problems - and attempts to date have not been successful. In 2004 the group of researchers led by the Korean veterinary surgeon Hwang had reported the successful cloning of human cells. However, this proved to be fraudulent.
In innovative lines of research scientists try to derive human embryonic stem cells without making use of cloning techniques. By parthenogenesis a human egg cell shall be encouraged to divide without adding sperm. Out of embryos developing that way stem cells can be derived, which can differentiate in many different kinds of cells again. So far this procedure was successfully performed with mice.
Additionally in other lines of research scientists try to avoid possible ethic concerns regarding the usage of embryos when deriving stem cells. For this purpose stem cells shall be cultivated, which beforehand got isolated from amniotic fluid. This is the description, that out of such cells human fat, muscle, nerve and liver cells were derived.
- What are the open questions and problems?
For both embryonic stem cells and adult stem cells, the following criteria must be considered with regard to their possible clinical applications:
- Proliferability: it must be possible to proliferate the stem cells in sufficient numbers.
- Differentiability: it must be possible to stimulate their differentiation into the required cell types.
- Purity: it must be possible to generate differentiated cells of one cell type only; i.e. pure cells instead of cell mixtures.
- Targeted integratability: it must be possible to transplant the cell or tissue replacement into the correct part of the body.
- Ruling out tumour formation: it must be guaranteed that there is no uncontrolled transplant growth or risk of tumour formation.
- Long-term therapeutic efficacy: the transplants must prove their functionality in the organism and their therapeutic effects on a long-term basis.
- Immune tolerance: the cell transplants should not be rejected by the immune system of the transplant recipient.
Research on human embryonic stem cells is still at its very beginning. Finding answers to the following questions arising from basic research is the precondition for any application in regenerative medicine:
- How can embryonic stem cells be derived efficiently?
- Do all embryonic stem cell lines show the same properties?
- How can embryonic stem cells be genetically modified?
- How can the differentiation of daughter cells be regulated?
- What new methods and tools are needed in order to measure and control this differentiation in vivo and in vitro?
- Are there alternatives to research involving human embryonic stem cells?
Tissue-specific adult stem cells, including stem cells from umbilical cord blood, are discussed as the main alternatives to research on human embryonic stem cells.
In the context of basic research the main focus lies on the cultivation, differentiation and manipulation of human embryonic stem cells. These specific properties can only be found in embryonic stem cell lines; adult stem cells are not viable alternatives in this area.
To date, a number of therapeutic methods have emerged from the field of tissue replacement from adult stem cells. Some of them have already been successfully applied to clinical uses for a long time, e.g. bone marrow transplantation in the wake of radiotherapy (haemopoietic stem cells) or skin regeneration after burns (dermatogenic stem cells). However, this cannot lead to the conclusion that adult stem are particularly well suited for the realisation of the clinical research goals mentioned above. For the assessment of their suitability the above-mentioned criteria of proliferability, purity, differentiability, etc. are the determining factors.
From today' s perspective it can be assumed that adult stem cells are, in terms of purity, risk of tumour formation and immune tolerance, better suited for clinical uses than embryonic stem cells. On the other hand, in terms of proliferability and differentiability, embryonic stem cells offer advantages. With regard to immune tolerance, embryonic stem cells from SCNT blastocysts are very likely to be similar to adult stem cells. Currently it is not possible to give a substantiated estimation from a scientific point of view which would give one of the two lines of research priority over the other in terms of their clinical application opportunities.
- Selected National and International Laws and Regulations
- Key Issues in the Ethical Discussion
- further references (DRZE Bioethic-Links)
- further literature by online search in BELIT
II. Selected National and International Laws and Regulations
1. International Regulations
On neither the level of the United Nations (UN / UNESCO) nor of Europe (Council of Europe / European Union) are there any directly relevant regulations concerning research with human embryonic stem cells. There are, however, on both levels opinions and regulations or regulatory efforts concerning the use of cloning methods in humans. These documents are therefore indirectly also relevant for human embryonic stem cell research. Moreover, there are relevant regulations linked to the European Union Sixth Framework Programme for Research governing the Community support for research with human embryonic stem cells.
- UN / UNESCO
Pursuant to article 11 of the Universal Declaration on the Human Genome and Human Rights of UNESCO of 11th November 1997 "practices which are contrary to human dignity, such as reproductive cloning of human beings, shall not be permitted. States and competent international organizations are invited to co-operate in identifying such practices and in taking, at national or international level, the measures necessary to ensure that the principles set out in this Declaration are respected." The formulation chosen here leaves open the evaluation of the use of cloning methods for non-reproductive purposes, for instance for the purposes of deriving embryonic stem cells. The declaration is not legally binding but recommendatory in character.
In its report "The Use of Embryonic Stem Cells in Therapeutic Research" of 6th April 2001 the International Bioethics Committee (IBC) of UNESCO observes that the question of regulating research involving human embryonic stem cells was an ethical question and that it was not only the right but also the obligation of each individual society to discuss this question in its own right. Against this backdrop, the IBC encourages governments to promote free and informed public debates in all countries. The Committee recommends that in those countries where embryo research is allowed, it should be subject to state regulation in order to ensure adequate respect of the ethical principles. According to the Committee's recommendation the use of so-called "surplus" embryos for stem cell research should be tied to the free and informed consent of the donors and research projects should be reviewed by Ethics Committees. Furthermore, the IBC advocates the careful assessment of advantages and risks of alternative methods of stem cell derivation. The report reiterates that cell nuclear transfer should only be used in conjunction with therapeutic research.
- Council of Europe
Pursuant to article 18 (2) of the Convention for the Protection of Human Rights and Dignity of the Human Being With Regard to the Application of Biology and Medicine: Convention on Human Rights and Biomedicine submitted for signature on 4th April 1997, "the creation of human embryos for research purposes is prohibited." Article 18 (1) states that "where the law allows research on embryos in vitro, it shall ensure adequate protection of the embryo."However, the term 'adequate protection' is not defined in detail. Hence, Member States are at liberty to undertake the conditional authorisation of research with "surplus" embryos. The Convention has not yet been signed by Germany, amongst other countries.
The Additional Protocol on the Prohibition of Cloning Human Beings prohibits in article 1 (1) "any intervention seeking to create a human being genetically identical to another human being, whether living or dead." Pursuant to the definition given in article 1 (2) "the term 'human being genetically identical to another human being' means a human sharing with another the same nuclear gene set." The Member States disagree as to whether an embryo created by way of 'therapeutic cloning' in order to derive stem cells should be regarded as a "human being" and, if so, whether these forms of cloning and stem cell derivation also come under the ban formulated here. According to the Additional Protocol the decision was, "to leave it to domestic law to define the scope of the expression "human being" for the purposes of the application of the present Protocol."
- European Union
The European Group on Ethics in Science and New Technologies (EGE), set up by the European Commission, states in its Opinion on the Ethical Aspects of Human Stem Cell Research and Use of 14th November 2000 that "in the context of European pluralism, it is up to each Member State to forbid or authorise embryo research. In the latter case, respect for human dignity requires regulation of embryo research and the provision of guarantees against risks of arbitrary experimentation and instrumentalisation of human embryos." In the countries where it is permitted, it should be placed "under strict public control by a centralised authority - following, for instance, the pattern of the UK licensing body (the Human Fertilisation and Embryology Authority)." Moreover, the group deems "the creation of embryos with gametes donated for the purpose of stem cell procurement ethically unacceptable, when surplus embryos represent a ready alternative source." The group also declares "that, at present, the creation of embryos by somatic cell nuclear transfer for research on stem cell therapy would be premature since there is a wide field of research to be carried out with alternative sources of human stem cells (from surplus embryos, foetal tissues and adult stem cells)."
On 30th September 2002 the Sixth Framework Programme of the European Community for Research, Technological Development and Demonstration Activities, Contributing to the Creation of the European Research Area and to Innovation (2002 to 2006) was approved. One of the areas supported by this Programme includes life sciences, genomics and biotechnology. According to the Decision of the European Parliament and of the Council of 27th June 2002, the fundamental ethical principles must be respected in carrying out research activities within the programme as laid down in the Charter of Fundamental Rights of the European Union and the Convention on Human Rights and Biomedicine of the European Council as well as the Additional Protocol on the Prohibition of Cloning Human Beings. Pursuant to a Council Decision of 30th September 2002 "research activities intended to create human embryos solely for the purpose of research or for the purpose of stem cell procurement, including by means of somatic cell nuclear transfer" are to be excluded from Community support. Moreover, "any research project involving the use of human embryos and human embryonic stem cells, following the ethical review" by the European Commission "will be submitted to a Regulatory Committee." The formulation of detailed implementing provisions by the Council was planned to be completed by 31st December 2003. On the same day, the European Commission declared that, during this period and up to the formulation of implementing provisions, it was suspending the promotion of human embryo or human embryonic stem cell research projects with the exception of studies involving human embryonic stem cells or human embryonic stem cells isolated in cultures or in stem cell banks.
On 9th July 2003 the European Commission submitted a draft regulation to the Council. The European Parliament responded on 19th November 2003 with a proposal for a legislative resolution. The European Commission proposal envisaged that only surplus embryos created earlier than 27th June 2002 could be used in research activities supported by EU funding. According to the proposal for a resolution of the European Parliament research involving human embryonic stem cells should only be financed, if the embryos used for this purpose were "'surplus' early stage (i.e. up to 14 days) human embryos." A deadline, however, was rejected. In its deliberations on 26th November and on 3rd December 2003 the Council was unable to reach agreement on the implementing provisions. On 18th February 2004 Research Commissioner Philippe Busquin declared in an interview that, for the time being, the Commission refrained from promoting the controversial creation of human embryonic stem cells.
Last but not least the question about a possible patentability of stem cells became of current interest. While the Federal Patent Court reached clarification in 2006 in Germany, the question about a European stem cell patent still remains.
- The International Society for Stem Cell Research (ISSCR)
The International Society for Stem Cell Research (ISSCR) was founded in 2002. It is an independent, non-profit organisation and tries to foster the exchange of information on stem cell research. On February 1st 2007 the ISSCR published a catalogue of standards for the work with human embryonic stem cells. Researchers shall via self-commitment adhere to this provision, furthermore abandon cloning humans for reproduction purposes. Only under strict regulations mixed beings of human and animal (chimeras) shall be produced and the payment for egg cell donations reduced. Beyond that ISSCR wants to achieve that only such surveys where those conditions were kept, will be published by well known magazines.
2. Regulations in individual countries
For more details of the regulations governing stem cell research in individual European countries, and also around the world, please see the expert report Vol. 3, DRZE-Sachstandsbericht "Präimplantationsdiagnostik, Embryonenforschung, Klonen - Ein vergleichender Überblick zur Rechtslage in ausgewählten Ländern".
If nothing else, the question about a possible patentability of stem cells has become up-to-date. While the German Federal Patent Court has arranged for clarity in 2006, the question about a European stem cell patent remains unanswered.
Stem cell research in Belgium is regulated by the Act regarding Research on Embryos in vitro of 11th May 2003. Accordingly, research on embryos within 14 days of fertilisation is permitted by law in Belgium. This is subject to the condition that therapeutic goals are pursued with the research and that insights are gained into the prevention or treatment of disease. The obtaining of new insights in the areas of fertility, sterility and organ/tissue transplantation also constitutes grounds for conducting research on embryos in vitro, if no other research methods promise results of equivalent quality. The creation of embryos purely for research purposes is generally prohibited, although permitted if the available surplus embryos do not meet the needs of the research project.
The Embryo Protection Act, which came into force on 1st January 1991, prohibits the production of an embryo "for any purpose other than the bringing about of a pregnancy." Furthermore, it bans the use of an embryo "for a purpose not serving its preservation". The Act makes it a punishable offence to cause "artificially a human embryo to develop with the same genetic information as another embryo, foetus or deceased person." An embryo is defined in this context as "each totipotent cell removed from the embryothat is assumed to be able to develop into an individual under the appropriate conditions for that". The Act thus bans the creation of embryos for research purposes. In the same way, the use of embryos for the production of stem cells, i.e. not for the purpose of their preservation, is also prohibited. The ban applies independently of whether these stem cells are totipotent or not and also extends to 'surplus' embryos. Whether the Embryo Protection Act also prohibits 'therapeutic cloning' or whether there is a regulatory gap is subject of a controversial debate amongst legal experts.
The import and the utilisation of embryonic stem cells, which are not totipotent, are regulated in the Stem Cell Act adopted on 28thJune 2002. According to this Act, the import and utilisation of these cells are only admissible subject to specific preconditions: They must have been "derived before 1st January 2002 in the country of origin in accordance with relevant national legislation there;" and the embryos from which they were derived must "have been produced by medically-assisted in vitro fertilization in order to induce pregnancy." Moreover, they must "definitely no longer (be) used for this purpose." Apart from these stipulations the Act also lays down that "no compensation or other benefit in money's worth may have been granted or promised" for the donation of these embryos. Research activities involving stem cells must serve "eminent research aims" and must "have been clarified as far as possible through in vitro models using animal cells or through animal experiments." Lastly, there must be scientific reasons to believe that "the scientific knowledge to be obtained from the research project concerned" can only be expected to be gained by using no other cells but embryonic stem cells." The question whether the preconditions are fulfilled must be considered " by a competent agency in its portfolio determined by ordinance by the Federal Ministry for Health." This agency will be advised by an independent, multi-disciplinary "Central Ethics Commission on Stem Cell Research."
Pursuant to a corresponding ordinance of 18th July 2002, the competent authority is the Robert Koch Institute (RKI). A regularly updated overview of the research projects approved to date can be accessed on the RKI website (as at 28th August 2007: 23 approvals).
The limited use made of the increased support available for stem cell research from EU funding is viewed as a special problem facing German researchers. Due to the restrictive legislation there have been only a few instances where German researchers are able to access EU support for stem cell research.
After long controversial discussions the German Bundestag agreed on the 11th April 2008 about an alteration of the stem cell law. With that the postponement from the 1st January 2002 to the 1st May 2007 of the key date regulation with regard to importing embryonic stem cells was enacted. The position papers of the German Research Foundation (DFG) and the German National Ethics Council of the years 2006 and 2007 gave new impetus to the discussion and the eventual amendment of the law.
Another problem is the patenting of Stem Cell research techniques and results. In 1999 the scientist Prof. Oliver Brüstle from Bonn got the patent for the technique of developing neuronal stem cells from human embryos. Greenpeace brought a charge that the patent was 'contrary to public order' because of killing human embryos. On 5th December 2006 the Federal Patent Court has revoked the patent on a method for generating a class of human embryonic stem cells. It declared the granted patent as partly cancelled: the patent is no longer valid for developing cells that originate from human embryos. But it is still valid for the extraction of cells originating from stem cells, which are not gained from embryos, but from germ cells.
Loi no. 94-654, article L. 152-3 of 29th July 1994 permits the in vitro creation of an embryo only in conjunction with medically-assisted reproduction. Hence, the in vitro creation of an embryo for research purposes is prohibited. This ban is again explicitly formulated in article L. 152-8, an article which lays down a general prohibition of any form of research involving embryos. Research of this type can only be allowed by way of an explicit exception. Preconditions for such an exception are: the embryo will not suffer any harm, the research has a medical implication and both parents as well as the competent regulatory committee have given their prior approval. Consequently, any derivation of human embryonic stem cells which may cause damage or harm is banned. The import and utilisation of human embryonic stem cells are, however, not prohibited.
On 11th December 2003 the National Assembly adopted a revised version of the 1994 bioethics laws on second reading. These laws included Loi n° 94-654. The bill continued to stipulate a ban on embryo-consuming research. However, it was envisaged that this prohibition would be suspended for five years.
On 8th July 2004 the National Assembly and the Senate passed the new French bioethics law (Loi n° 2004-800 6th August 2004). As provided by the bill, the new regulations also essentially confirm the 1994 ban on research involving stem cells and embryos. Nonetheless, research on surplus human embryos is to be permitted for a period of five years. During this time research involving human embryos and the obtaining of human embryonic stem cells are to be allowed subject to certain conditions. They include a requirement that the embryo was created in vitro in order to induce a pregnancy and is no longer being used for this purpose. Moreover, the research projects must facilitate the attainment of significant therapeutic progress which - according to the current level of scientific knowledge - cannot be achieved with comparable efficiency using alternative means.
Compliance with these regulations is monitored by a competent agency, the Agence de la biomédicine. The import and export of human embryonic stem cells also requires the authorisation of the Agence de la biomedicine.
Furthermore, all forms of human cloning remain banned.
- United Kingdom
According to the Human Fertilisation and Embryology Act of 1990 embryos may be used for research purposes subject to certain conditions. They may also be created through cell nuclear transfer, i.e. 'therapeutic cloning'. These conditions stipulate that the genetic parents must give their consent and that the embryo cannot yet have developed a primitive streak or be older than 14 days. Furthermore, a licence must be granted by the competent regulatory authority, the Human Fertilisation and Embryology Authority (HFEA). Licences are granted on condition that the research project aims to improve infertility treatment or contraception methods, to increase knowledge about the causes of miscarriages or hereditary diseases or to develop methods to identify genetic or chromosomal abnormalities in embryos prior to implantation. With regard to these goals, the project must be without alternative.
As a consequence of the Human Fertilisation and Embryology (Research Purposes) Regulations which came into force on 31st January 2001, the list of research aims eligible for a licence in conjunction with research using human embryonic stem cells was extended. According to these Regulations, the use and also the creation of embryos for research purposes may also be licensed if the research project aims at improving knowledge about embryonic development or about serious diseases, or at the application of such knowledge to the treatment of serious diseases. A continually updated list of research projects involving human embryonic stem cells, which have been licensed to date, can be accessed on the HFEA website (as at 16th September 2005: 33 licenses).
The current discussion about stem cells in Great Britain concerns about new research applications which were made to the HFEA, in which the license to produce and research animal/ human cross creatures animal/ human cross creatures (hybrids) is the subject matter.
- The Netherlands
Stem cell research in the Netherlands is regulated by the 2002 Embryos Act. Research on already existing stem cell lines was previously permitted, although the rules needed amendment. While the Embryos Act prohibits the creation of embryos for research purposes, research on human embryonic stem cells is allowed. To this end stem cells may be obtained from so-called surplus embryos up to 14 days after fertilisation and with the parents' prior consent. Such derivation of stem cells and also their use for research require the authorisation of the regulatory agency, the Central Committee for Research Involving Human Subjects (CCMO).
Swedish legislation ranks amongst the most liberal in the world with respect to research on human embryonic stem cells. Research on human embryonic stem cells from so-called surplus embryos is permitted under the In Vitro Fertilisation Act No. 115 of 14th March 1991. These embryos must, however, be destroyed 14 days after they were obtained and may not be implanted in a uterus. The donors' consent is also required.
Following a national referendum on 28th November 2004 research on embryonic stem cells in Switzerland has been regulated by the Stem Cell Research Act (Stammzellenforschungsgesetz - StFG) of 19th December 2003. The Stem Cell Research Ordinance (Stammzellforschungsverordnung) puts the law into concrete form and sets out, inter alia, the conditions for approval of a research project involving stem cells. While the regulations prohibit the creation of embryos purely for research cells, stem cells may be obtained from surplus embryos until the seventh day of their development, provided both parents give their consent and the Federal Office of Public Health (Bundesamt für Gesundheit) authorises the research project in question. The subject of the research project must be the identification, treatment and prevention of human diseases or human developmental biology. In this context, it must be ensured that insights of an equivalent quality cannot be obtained by other means and that the project is ethically acceptable. In addition, embryonic stem cells obtained from surplus embryos may be imported from abroad for research purposes subject to the approval of the Federal Office of Public Health. Stem cells may only be exported if the prevailing legal situation in the destination country is in accordance with Swiss research conditions.
In the United States research involving human embryonic stem cells is not as yet explicitly regulated on the federal level. Instead, legislative powers in this respect are in the hands of the individual states. Special significance attaches here to California, which in 1997 initially prohibited the cloning of human cells - the first US state to do so - and then re-legalised cloning for research purposes subject to certain conditions with the amendment of the Health and Safety Code in 2004. At present, there are no US Federal laws prohibiting either research involving human embryonic stem cells or their derivation from embryos.
The legislation 2001 by the former president George W. Bush enacted restriction concerning the federal funding of research involving human embryonic stem cells was overruled in March 2009 by the current president Barack Obama. At that time Bush prohibited federal funding for such research projects using new human embryonic stem cells. He announced that only research involving stem cell lines established before 9th August 2001 is eligible for funding. Furthermore, these stem cell lines must have been derived from surplus embryos originally created solely for reproduction purposes and their use must meet with informed consent of the donors. Unlike Bush, Obama wants to subsidise stem cell research with federal funds without restrictions.
Several federal laws are currently pending in the US Congress relating to research involving human embryonic stem cells. On 27th February 2003 the House of Representatives adopted the bill prohibiting human cloning. The ban on human cloning envisaged in this bill refers to the transfer of nuclear material from a human somatic cell to an enucleated oocyte or to an oocyte with a deactivated nucleus. The consequence of this procedure would be the creation of a living organism which - irrespective of the stage of its development - in genetic terms, would be virtually identical with a living or deceased human being. Hence, the bill contains a ban on 'therapeutic cloning'. Furthermore, it makes the utilisation and import of embryos produced in this way or any products developed from them punishable offences. The Senate has not yet adopted the bill.
An overview of the bills currently pending in Congress in connection with research involving human embryonic stem cells can be accessed on the website of the National Institutes of Health (NIH).
On 18th July 2006 the United States Senate voted 63 to 37 in favour of a new bill to lift restrictions on stem cell research dating from 2001. The House of Representatives had previously passed the bill in May. The intention was that stem cell research could now also receive support from public funds. President George W. Bush then blocked the law on 19th July by exercising his power of veto for the first time in his term of office. Bush justified his veto by noting that this law would destroy human life in order to perhaps help other people. The President recommended embryo adoptions as a means of dealing with so-called surplus embryos. The bill to expand stem cell research can now only be adopted with a two-thirds majority in Congress.
- Medical and Scientific Aspects
- Key Issues in the Ethical Discussion
- further references (DRZE Bioethic-Links)
- further literature by online search in BELIT
III. Key Issues in the Ethical Discussion
A proven method of the ethical assessment of an action involves on the one hand asking whether the goals pursued with this action are legitimate and on the other hand examining whether the means used to achieve these goals are justifiable.
There is widespread agreement that the goals pursued in research involving human embryonic stem cells, both in fields of basic biological research and therapeutic research, are not only legitimate, but also eminent, i.e. 'high-ranking' (cf. part I: "Medical and Scientific Aspects"). Opinions differ, however, on the question of the justifiability of the means used in this research, if they involve the utilisation and - according to state-of-the-art technology - also the destruction of human embryos.
One manifestation of this disagreement is, for instance, the great diversity of national and international regulatory models and their current discussion (cf. Part II: "Selected national and international laws and regulations").
The discussion mainly focuses on the question of how far human embryos are particularly worthy of protection and whether their protection status permits using embryos for the derivation of stem cells or even producing them especially for this purpose (1). Granting a possible inadmissibility of embryo-consuming research leads on to the ensuing question of whether this also applies to "surplus" embryos (2) or to cell nuclear transfer embryos which are not created by the 'conventional' nuclear fusion of two germ cells (3). Finally, as assessing the justifiability of the means also depends on the availability of other means, the discussion of possible alternatives also plays an important role (4).
1. The question about the worthiness of protection of the human embryo
The debate about the worthiness of protection of the human embryo is characterised by two different fundamental positions.
At the heart of the first position lies the conviction that from the moment in which nuclear fusion is completed, i.e. right from the beginning, the embryo is entitled to the same protection status as that accorded to human beings after birth on the basis of their personhood. The moral status of the early embryo is thus determined on the basis of the autonomous subject into which he or she may potentially develop. Accordingly, embryos must never be instrumentalised for other purposes, irrespective of the embryos' developmental stage or how eminent the purposes may be.
Following the second fundamental position, the embryo first needs to reach a specific stage in its development before it is entitled to the same protection status granted to human beings after birth on the basis of their personhood. Prior to this stage, embryos are only entitled to a graduated protection level.
Accordingly, embryo-consuming research using embryos that have not reached the relevant developmental stage requires justification, but is not ruled out entirely on moral grounds. As a consequence, this type of research is not only morally admissible, but is even imperative if the research goals are sufficiently eminent and if there are no alternative means. The same applies to the creation of embryos for research purposes.
Advocates of the first position generally draw on the following lines of reasoning . Firstly, they argue that right from the beginning the embryo has the potential to develop into a person (potentiality argument). What is more, following completion of nuclear fusion the embryo develops into a person in a continuous process. Hence, if one seeks to avoid arbitrary assertions, the commencement of protection worthiness can also only be located at this point in time (continuity and identity argument). Not only that, the proponents of this position point out that it would be a violation of the fundamental principle of human dignity to make worthiness of protection dependent on a property other than that of being a human being (species affiliation argument).
Supporters of the second position, which only accord the embryo full worthiness of protection when it reaches a specific stage of development, vary in their definition of this specific stage. Some consider the moment of nidation in the uterus as the decisive factor, because the embryo would only be truly able to develop from this point onwards. Others define the formation of the primitive streak as the decisive criterion: only then could the possibility of a multiple pregnancy be ruled out and the individuation process was completed. A third group of proponents considers the development of the neuronal preconditions for such capacities as pain sensation or the ability to develop interests to be the decisive factors. They argue that without these capacities it was impossible to establish any claims, even less so to justify any related claims to protection.
The German Embryo Protection Act is based on the first position which prohibits the creation of embryos for research purposes and the use of embryos for purposes other than their preservation. The British regulations - the Human Fertilisation and Embryology Act of 1990 and the Human Fertilisation and Embryology (Research Purposes) Regulations of 2001 - are based on the second position. Under certain further conditions, they not only allow the use of surplus embryos for defined research goals up to the formation of the primitive streak, but also to create embryos for these very purposes.
2. The question about the admissibility of research involving so-called 'spare' embryos
In many countries in which in vitro fertilisation treatments are permitted and carried out, the problem of the so-called 'surplus' embryos arises. These are embryos which are created in the course of in vitro fertilisation (IVF), but which are not transferred to the uterus and are no longer needed by the parents - either because the mother has developed a disease or has died or because she has abandoned the idea of transfer.
Should the use of such embryos for the derivation of stem cells and their destruction in this process be permitted?
Supporters of their use for stem cell derivation argue that this does not constitute an inadmissible instrumentalisation. These embryos would not have the chance to develop into a child anyway and were consequently "doomed to die." The only remaining options were to let them die or store them for an unlimited period.
Opponents have their doubts whether such embryos are necessarily "doomed to die." They point out the possibility of embryo adoption. Furthermore, they fear that permitting the use of such "surplus" embryos for stem cell derivation could tempt IVF providers and also IVF users in future to produce even more embryos in order to make them available to research.
Those in favour of such a permission counter that the artificial creation of surplus embryos could be prevented by adequate legal regulations. They reject embryo adoption mainly on the grounds that gestational motherhood involves considerable risks for the child. Moreover, they point out that releasing these embryos for adoption could lead to disguised surrogate motherhoods, enforced adoptions and commercialisation. Apart from this, they maintain that embryos which are preserved by cryo-conservation over a longer period of time may suffer damage which could prevent further development. These embryos were, therefore, unsuitable for embryo adoption.
[Translate to English:] 3. Die Frage nach der Zulässigkeit der Forschung mit Kerntransfer-Embryonen und ihrer Erzeugung
Die Entwicklung vielseitiger patientenspezifischer Therapieverfahren bisher unheilbarer Krankheiten verspricht man sich durch den Einsatz spezifisch klonierter Stammzellen. Die Technik ihrer Gewinnung (Zellkerntransfer) sowie die rechtlichen Regelungen ihrer Verwendung und die ethische Diskussion werden im Blickpunkt "Klonen zu Forschungszwecken" dargelegt.
Stem Cell Research
Medical and Scientific Aspects
- Written by Herbert Püttmann (2004), fundamentally revised by Simone Hornbergs-Schwetzel (2006), revised by Simone Hornbergs-Schwetzel (2007, 2008)
Selected National and International Laws and Regulations
- Written by Ingo Hillebrand (2004), revised by Simone Hornbergs-Schwetzel (2006), (2007), (2008) and Sebastian Mutke (2008), revised by Lisa Tambornino (2009)
Key Issues in the Ethical Discussion
- Written by Ingo Hillebrand (2004), revised by Simone Hornbergs-Schwetzel (2006, 2007, 2008)