Research Cloning

I. Medical and Scientific Aspects

The sexual reproduction for many living organisms takes place through the formation and recombination of germ cells (sperm cells and egg cells). A new genome originates from the composition between paternal and maternal genotypes. The term “cloning” is in contrast a form of asexual or vegetative multiplying, in which the genome of the respective organism is duplicated. In the process of cloning, there is no reorganization (recombination) of genes; rather a nearly or even completely identical genetic “copy” of the original organism arises. Beside sexual reproduction, cloning is a usual way of reproduction for many invertebrates and for most plants. The natural occurrence of identical twins (monozygotic twinning) in humans is also considered a form of identical multiple formation, yet it occurs only in the context of sexual reproduction.

In the laboratory, organisms can be cloned in different ways. One way is the division of already existing embryos, meaning through embryo splitting. Another method is the creation of an embryo by means of cell nuclear transfer. A further procedure is known from the generation of so-called transgenic mice, namely the tetraploid complementation assay. Beside these variations in the cloning technique, different purposes of cloning should be differentiated, namely between research and therapeutic cloning on the one side, and reproductive cloning on the other side. In all cloning techniques a genetically identical duplicate is produced: the duplicate of a DNA fragment or molecule, a cell, a tissue or in the case of reproductive cloning, a complete organism.

The object of this focal point is cloning for research and therapeutic purposes. Reproductive cloning, however, is only considered insofar as the techniques are identical to a certain degree.

To avoid possible misunderstandings, the term therapeutic cloning, which dominates the public debate, will be substituted and complemented with the term “research cloning” in the following text. A major part of the current research does not aim at concrete therapeutic purposes; rather it mainly belongs to the field of basic research. This basic research can and should lead to the development of new therapies on the long run, but is also used above all to achieve a basic understanding of the scientific relevant processes.

What is research cloning or therapeutic cloning?

Different methods are summarized under the term “research cloning” or “therapeutic cloning” such as cell nuclear transfer, the reprogramming of differentiated cells and embryo splitting.

Using Somatic Cell Nuclear Transfer (SCNT), the nucleus of any somatic cell is transferred into an egg cell whose nucleus has been removed. The nucleus can be isolated from practically any adult somatic cell of a donor. The egg cell gained by means of puncture from the ovaries of a donor after a special hormonal treatment is then enucleated. The enucleation takes place using a micro pipette which sucks off the nucleus of the egg cell and substitutes it with the nucleus extracted from the somatic cell. The transfer of the new nucleus takes place through injecting the nucleus into the cytoplasm of the egg cell. The egg cell sends out impulses whose mode of action is so far unknown. These impulses bring about a reprogramming of the cell nucleus which causes the nucleus to lose its specialization. This way the nucleus will be restored from its already differentiated state back to the state which enables the development of the embryo.

Considering the genetic material contained in the nucleus, the cloned embryo is genetically identical with the donated nucleus. The Mitochondria, i.e. the cell components which serve the production of energy inside the cell, are derived from the egg cell. The clone developed as a result of the cell nuclear transfer is genetically almost completely identical with the donor of the transferred nucleus. A complete identity is only accomplished, when the donor of the nucleus and the donor of egg cell are genetically identical.

The method of cell nuclear transfer gained recognition through the results of the team of Ian Wilmut's research team. The team succeeded in 1997 for the first time in producing and fully developing a mammal-embryo by means of transferring the nucleus of an adult somatic cell into an enucleated egg cell. The cloned sheep Dolly stands for the success of the research, yet also for the possibility of using the cloning technique for reproductive purposes which are ethically extremely controversial.

In addition, one procedure has been known for many years now by means of which human somatic cells can be successfully reprogrammed so that they exhibit significant characteristics of embryonic stem cells. Such cells are called induced pluripotent stem cells (also known as iPS cells). Since the iPS cells are also genetically identical with the donor’s cells, this technique offers a less problematic alternative to therapeutic clones in ethical and legal terms. It is debatable whether iPS cells can evolve into totipotent cells under the condition of cell culture. However, the successful establishment of pluripotency from iPS cells of mice with the aid of the procedure of tetraploid complementation assay triggers discussion here. Considering these results, it is doubtful whether the procedure, with respect to its ethical permissibility, is brought more closely to research cloning as well as research on donated and artificially generated embryos.

With regard to the technical aspect, research cloning and cloning for reproductive purposes are not fundamentally different. However, it is decisive that the embryo in the case of research cloning is not implanted into the uterus in order to be born. Rather it gets destroyed in an early stage of the embryonic development (the blastocyst stage) so that embryonic stem cells can be extracted and differentiated in vitro into specific cell types. It is not inappropriate to describe the approach as “therapeutic cloning”, since there is the hope that the cells which have become available can at the end be transferred again to the donor organism for therapeutic purposes. Currently, cloning is, however, mostly conducted for research purposes, if it’s legally permitted at all.

Another method of producing genetically identical clones is the method known as embryo splitting. In this case, an embryo is split using microsurgery to artificially form twins or multiple embryos. Since cells are still totipotent at the beginning of embryonic development, this gives rise to two or more embryos, which continue to develop as an undivided embryo would, given a suitable environment. This method currently plays a more minor role in the field of research cloning.

What is the purpose of research cloning or therapeutic cloning?

A primary target of research or therapeutic cloning is the production of embryonic cells (ES-cells). These cells are of interest for the researchers because they can, under appropriate circumstances, be developed into almost all different kinds of somatic cells. This ability is described as pluripotency. It is controversial, whether the stem cells produced by means of cloning can become totipotent cells under cell culture conditions. An experimental evidence of totipotency of embryonic stem cells is prohibited for moral reasons, since it would be necessary to let a complete organism grow to maturity.

A long-term aim of research cloning is the production of autologous stem cells for therapeutic purposes. These are stem cells, whose genetic features are to a large extent identical with the genetic features of the patient to be treated. In this way it would be guaranteed that the cell or the tissue incorporated in the organism for therapeutic purposes is highly compatible with the immune system. Hence a number of complications which occur during the application of heterologous transplants (such as the case in organ donation) would be avoided. In particular it is hoped, in the case of research success, to be able to provide a transplantation medicine by means of the cloning technique by virtue of which the as of today still necessary long-term administration of immunosuppressivant would be unnecessary or at least diminished and the additional current scarcity of transplants would be relieved. However, in November 2014 researchers of the University Medical Center Hamburg-Eppendorf published in the journal Cell Stem Cell a study on mouse model in which a rejection reaction occurred after the transplantation of embryonic stem cells derived from a somatic cell nuclear transfer procedure. This is due to the mitochondrial differences between the transplanted cells and the ones of the receiver. Since mice show a comparably low variability in mitochondria, immune reactions are possibly to be expected in humans as well. According to opinion of researchers, the the method of somatic cell nuclear transfer (SCNT) still represents, however, a promising path to new therapies when the rejection reaction is solved. However, possible risks of the therapeutic application of cloned stem cells are indicated; in particular, that stem cell therapies can induce a tumor growth. A point will have to be clarified accordingly is whether and how the emergence of tumors can be prevented.

Also, the iPS cells which are genetically identical with the donor's cells are regarded as another favorite for the mentioned research purposes. However, the procedure is currently associated with risks which must first be eliminated before implementing it within a therapeutic framework. Moreover, it has been shown that there are greater differences after all between iPS cells and pluripotent ES cells than initially anticipated. More details are available under the focal point “Stem Cell Research”.

Status of Research

Experimentations in the field of research cloning took place for a long time exclusively in the shape of animal experiments. In 2000, Munise et al. reported for the first time about the successful cultivation of pluripotent embryonic stem cells in mice. For this purpose, they injected the genetic material of mice somatic cells into the enucleated murine egg cells and let the resulted clone grow to maturity until the stage of blastocyst. The embryonic stem cells extracted from the blastocyst were further cultivated in the petri dish and differentiated into nerve and muscle cells. These stem cells were subsequently marked and injected in mice embryos and in already full-grown mice. It has been proved that the cloned stem cells in the embryo of the mouse contributed to the development of brain, liver, lung, kidney and other organs and that they can also develop to build different tissue types inside mature mice.

The successful extraction of stem cells from previously cloned primate embryos was described for the first time at the end of 2007. Cell nuclei were transferred from skin cells of rhesus monkeys via cell nucleus transfer and inserted into enucleated egg cells. These stem cells developed into blastocysts, from which stem cells that were proven to be to a larger extent genetically identical with the original donor cells were be obtained. In all tested aspects, the cells corresponded to conventional embryonic stem cells and, according to the research group led by Shoukhrat Mitalipov, differentiated into cardiac muscle cells and nerve cells.

At the beginning of 2008 Tabar et al. published the results of a therapeutic experimentation on stem cells from a cloned embryo for the treatment of Morbus Parkinson in the mouse model. Embryos were cloned from the skin cells of mice with Parkinson's disease, of which stem cells were be extracted again and developed into specific nerve cells. These nerve cells were injected in the diseased donor mice, which showed no immune response, but rather a significant relief of the disease symptoms. It is uncertain whether these results obtained from animal experiments can be transferred to humans as well.

Likewise, an American research group led by Andrew French published at the beginning of 2008 for the first time the results of the successful cloning of human embryos. Thereby the nucleus of a human adult skin cell was removed and transferred into an enucleated egg cell. The researchers used 29 egg cell from three donors aged 20 to 24 for the experiment. The egg cells were donated by women, who donated them voluntarily when the egg cells became redundant after an IVF treatment. Five of the egg cells which were filled with the foreign genetic material developed blastocysts. This development was then interrupted by the scientists. The blastocysts prove the successful cloning which is represented in the genetic identity between the stem cell line and the donor cell.

In May 2013 the research group led by Masahito Tachibana and Shoukhrat Mitalipov extracted for the first time human embryonic stem cells from cloned embryos. The scientists had also transferred the nucleus of a human adult skin cell into a donor enucleated egg cell. By means of a systematically enhanced method, only a few egg cells were used for the study, and hence an early death of the embryo was prevented. The embryos were destroyed after a few cell divisions to extract the stem cells from them.

In April 2014 Robert Lanza from the biotechnology company ACT and Dong Ryul Lee from the Stem Cell Institute in Seoul issued the successful establishment of stem cell lines in a cloning process using differentiated cells of adults. They extracted the lines from skin cells of a 35-year-old man and a 75-year-old man. It was thus possible to show, compared to the previous year, that stem cells can also be extracted using cell material which already display numerous genetic and biochemical alterations as well as suspected damages to the DNA. The aim of this therapeutic cloning is to produce a genetically identical replacement tissue from the somatic cells of the patients which does not get rejected.

An overall goal of basic research in the field of therapeutic cloning lies in increasing the efficiency of somatic cell nuclear transfer techniques as well as expanding the number of iPS cells  that can be obtained through reprogramming.

The creation of human-animal hybrids or human-animal chimera represents an additional field of research. The procedure of egg cell retrieval involves the administration of high doses of hormones and is associated with risks. In order to avoid the problems related to the use of human oocytes, alternative egg cell sources are being researched.

In early 2008, a British research team led by the stem cell scientist Lyle Armstrong produced embryos from a human genetic material, derived from skin cells, and egg cells, derived from cows. The goal of these controversial experiments is to determine the possibility of using animal oocytes and embryos instead of human ones for the cultivation and differentiation of stem cells as well as the furthering of the therapeutic application of this procedure.

Studies on embryos with cells of both animal and human origin have since been pursued and widely criticised. Recent studies are no longer aimed at using animal oocytes, but at gaining human tissue, at best whole organs from animal embryos, in which human stem cells are to evolve in vivo. Prior to this, the genetic sequences responsible for the formation of certain organs are ‘deactivated’ by genetic modification of the animal embryos. In their place, the introduced human induced pluripotent stem cells (iPS cells) integrate and at best, form the respective organ based on human cells.

II. Legal aspects

From a legal standpoint, the production of cloned human embryos for obtaining embryonic stem cells touches on issues of embryo protection and the use of cloning methods on humans. Furthermore, it also raises questions in terms of patent law.

Yet national regulations alone are not the only regulations of relevance in this case. Due to the increasing internationalisation of research and practice in the field of bioscience, it is essential that international regulations and declarations are also taken into consideration. Although, at the present time, these regulations are seldom legally binding, they frequently provide a framework for developing legislation at national level. 

1. Internationale Regelungen

There are currently no concrete, binding regulations governing the use of cloning methods on humans at either the level of the United Nations (UNO / UNESCO) or on the pan-European level (Council of Europe / European Union). However, on both levels there are pertinent regulatory attempts as well as opinions/statements that - while not legally binding - have the status of recommendations.

Article 11 of the Universal Declaration on the Human Genome and Human Rights adopted by UNESCO on 11 November, 1997, states that “practices which are contrary to human dignity, such as reproductive cloning of human beings, shall not be permitted”. The legal status of cloning for research purposes is thus left open. 

On 8 March, 2005, the General Assembly of the United Nations adopted the Declaration on Human Cloning on the basis of the recommendation of the Sixth Committee (Legal) of 24 February, 2005. It includes a call to all UN Member States to take all measures necessary to prohibit all forms of human cloning, including cloning for medical purposes, so-called “therapeutic cloning”. The Declaration states that all forms of human cloning are incompatible with human dignity and the protection of human life. The vote reflects the deep division between supporters and opponents of the Declaration. Supporters consider it a milestone for the protection of human dignity and promotion of human rights. Opponents criticised the linking of the ban on reproductive cloning with the ban on cloning for medical purposes, believing that an important opportunity to adopt a legally binding convention on the worldwide prohibition of reproductive cloning had been missed. The current Declaration is not binding and merely has the status of a recommendation. Representatives of governments that voted against the Declaration - including China, Belgium and the United Kingdom - made it clear that the decision would have no effect on their position with regard to “therapeutic cloning”. 

The draft resolution had been tabled in 2003, initially by Costa Rica, with a call for a comprehensive ban on all forms of human cloning, including “therapeutic cloning”. The counterdraft proposed by Belgium similarly included a ban on reproductive cloning, but it left the decision on “therapeutic cloning” to the discretion of individual national governments. In November 2004, despite protracted negotiations, neither of the draft resolutions was able to secure a majority.

Council of Europe
The pertinent passage in the Convention on Human Rights and Dignity of 4 April, 1997, reads "the creation of human embryos for research purposes is prohibited" (Art. 18 §2). This refers to any form of creation, hence also those created through embryo splitting and cell nuclear transfer. § (1) of the same Article allows research on human embryos provided “adequate protection of the embryo” is ensured under national legislation. The Additional Protocol of 12 January, 1998, on the Prohibition of Cloning Human Beings prohibits the creation of “a human being genetically identical to another human being, whether living or dead”. Germany is not to date a signatory to the Convention or the Additional Protocol.

European Union

Article 3 (2) of the Charter of Fundamental Rights of the European Union proclaimed by the European Parliament, the Council and the Commission on 7 December, 2000, prohibits reproductive cloning. The Explanations on the Charter state in this respect: “The Charter [...] prohibits [...] only reproductive cloning. It neither authorises nor prohibits other forms of cloning. Thus it does not in any way prevent the legislature from prohibiting other forms of cloning”. The Charter therefore adopts a neutral position on the creation of human embryonic stem cells through “therapeutic cloning”.

In its resolution on human cloning of 15 January, 1998, the European Parliament affirmed “that the cloning of human beings must be prohibited”. Furthermore, it calls on “the Member States of the Council of Europe to sign and ratify the Council of Europe Convention on Human Rights and Biomedicine and its Additional Protocol on the Prohibition of Cloning Human Beings”. In a further resolution on human cloning of the 7 September, 2000 the Parliament expresses the view “that ‘therapeutic cloning’, which involves the creation of human embryos solely for research purposes, poses a profound ethical dilemma, irreversibly crosses a boundary in research norms and is contrary to public policy as adopted by the European Union”. Resolutions adopted by the European Parliament have no legally binding force, although they normally exert a formative influence on future legislation and case law in the European Union.

2. Regulations in Individual Countries

A detailed overview of the legal situation in various countries is provided by the DRZE-Expert Report Sachstandsbericht “Präimplantationsdiagnostik, Embryonenforschung, Klonen - Ein vergleichender Überblick zur Rechtslage in ausgewählten Ländern” (German).

The biopolitical legal situation is characterized by a tense relationship between the legislation of the Commonwealth and the federal state on the one hand and the legislation of individual states and territories on the other hand. At the federal level the “Research Involving Human Embryos Act 2002” as well as  the “Prohibition of Human Cloning for Reproduction Act 2002” apply. Both laws provide a frame for specific legal regulation in the individual states. The “Prohibition of Human Cloning for Reproduction Act 2002” which is authoritative for research cloning, prohibits therapeutic as well as reproductive cloning. The creation of embryos containing DNA from more than two people as well as the development of embryos in laboratories in excess of 14 days after the fertilisation is prohibited. However, the Australian parliament repealed the research cloning prohibition in November 2006. So far research on stem cells was permitted to be carried out if the stem cells were derived from ‘surplus’ embryos before 2002. The Prohibition of Human Cloning for Reproduction and the Regulation of Human Embryo Research Amendment Act came into effect in 2006. It was revised and affirmed in 2008. Reproductive cloning remains prohibited in Australia. However, federal states can decide whether they approve cloning for research- and therapeutic ends. For example, research-cloning is permitted inter alia in the states of Victoria, New South Wales and Queensland.

In Belgium all forms of reproductive cloning are prohibited. In principle, cloning for research purposes is also prohibited pursuant to the “Law on Research on Embryos in vitro” (2003). However, since research on embryos in vitro is permitted within the first 14 days of life provided a therapeutic benefit can be attained with such research in the long term, embryos may be created artificially for research purposes. Nevertheless, this only applies if the research goals cannot be achieved solely using stem cells from so-called surplus embryos.

Important sources of law in Denmark are the law Nr. 460 of 6 June, 1997, the enactment Nr. 728 of 17 September, 1997, as well as the law Nr. 923 of 4 September, 2006. They provide for the restriction of biomedical research involving fertilised oocytes on studies that aim at the improvement of medically assisted reproduction, at the improvement of techniques for the detection of severe hereditary diseases or at gaining insights into treatment methods for human diseases. The goal is to respond to diseases in this spectrum, such as Parkinson's Disease, heart diseases or certain types of diabetes, with stem cell therapy of newly acquainted knowledge. Oocytes used for this purpose are allowed to be kept viable outside of the uterus for a maximum of 14 days after fertilisation (excluding cryopreservation). Reproductive cloning as well as experiments intended to facilitate human cloning are prohibited. Acting on behalf of the Danish Parliament (Folketing), the Danish Council on Ethics (Det Etiske Raad) provides some possible pointers in its statement on human cloning of 2001, as well as in the statement of 2010, as to whether this ban should be interpreted as referring to research cloning as well. In the statement of 2001 the Council expressed, inter alia, its opposition to therapeutic cloning. In conclusion to both statements, the Council recommends that research involving embryonic stem cells should be limited to stem cells derived from ‘surplus’ embryos created via artificial insemination.

Research cloning in France is regulated by the Public Health Code (Code de la santé publique) since 1994. The regulations stated therein were amended several times by bioethics laws (Lois relatives à la bioéthique). 

Since then, the production of embryos for research purposes and consumptive embryo research as well as cloning for research and reproductive purposes have been prohibited in France. With Law 2011-814 of 7 July, 2011 on bioethics, the legislation changed: research on embryos and embryonic stem cells is allowed under certain conditions. Inter alia, "surplus" embryos that resulted from in vitro fertilization and that are no longer intended for parenthood may be used for research purposes under a number of further conditions. The ban on reproductive cloning as well as research cloning remains in place under the bioethic laws enacted to date. For more information on the regulation of stem cell research in France, see the In Focus „Research with Human Embryonic Stem Cells“.

In the Federal Republic of Germany, the Embryo Protection Act (Embryonenschutzgesetz 1991) prohibits the production or use of embryos for any purpose other than to initiate pregnancy. What is more, all forms of manipulation performed on an embryo created outside the body that do not serve its preservation are prohibited. This means that all creation of and research involving embryos that does not serve the preservation of the embryo is banned. In addition, Section 6 (1) of the Act states: “Anyone who causes artificially a human embryo to develop with the same genetic information as another embryo, foetus, human being or deceased person will be punished with imprisonment up to five years or a fine.” Thus, the procedure of research cloning or therapeutic cloning using cell nuclear transfer is fundamentally prohibited by law. However, there is dispute amongst lawyers over how to interpret the term ‘same’ in the wording “with the same genetic information”. Depending on how the term is interpreted, the cloning ban laid down in Section 6 of the Embryo Protection Act might not encompass all types of cloning techniques and would thus permit certain cloning procedures. If the term ‘same’ in this legal wording is understood in the sense of ‘identical’, then an embryo cloned using cell nuclear transfer would not fall under Section 6 (1) of the Act. The genetic information of an embryo cloned in this manner is not completely identical to the genetic information of the nuclear donor as a minimal amount of foreign mitochondrial DNA from the donor egg cell is also passed on to the embryo. However, since the mitochondrial DNA only makes up around 0.01 to 0.02 percent of the whole genome, for quantitative reasons many authors advocate referring to ‘the same genetic information’, i.e. interpreting ‘same’ in the sense of ‘comparable’. As the legislative history for the 2002 Stem Cell Act suggests, legislators also assume that Section 6 (1) of the Embryo Protection Act likewise extends to embryos derived by cell nuclear transfer. 

In legal terms, the actual validity of the Stem Cell Act is undisputed. However, whether the Act is compatible with other laws and constitutional provisions has been the subject of controversial debate for some time now. Among other issues, the interpretation of the Federal Republic of Germany's Basic Law is controversial, namely: the constitutional issue of whether the full worthiness-of-protection status should apply to the human embryo from the moment of pronuclear fusion. 

The Federal Constitutional Court (Bundesverfassungsgericht) has hitherto expressed an opinion on the question of how far human dignity and the protection of life extend with respect to unborn life on two occasions in connection with court practice on abortion. In its first decision on abortion of 25 February 1975, the Federal Constitutional Court determined that the basic right to life defined in Article 2, paragraph 2 of the Basic Law also extends to unborn life and life “at least from the fourteenth day after conception (nidation, individuation)”. This formulation leaves open the question as to whether the basic right to life is also afforded to an embryo before the fourteenth day after conception. While the second decision of 28 May 1993, affirms that human dignity is “already [due] to the unborn human life”, the court expressly left unresolved the question of “whether, as insights of medical anthropology would suggest, human life arises prior to the fusion of egg and sperm cell”. Regulations governing abortion formed the subject matter of the proceedings. Consequently, only the term of the pregnancy, which “according to the [...] provisions of the Criminal Code [extends] from completion of the fertilised egg becoming implanted in the uterus [...] until the commencement of birth”, had a bearing on the decision.

Whether a human embryo should be protected from the “point of pronuclear fusion” or not until a later point in its development is considered to be insufficiently clarified at present due to differing protective regulations for an embryo depending on whether it is in vitro or in vivo. For some time now, the possibility of amending the Embryo Protection Act has been discussed among scientists and in the public realm.

The 1991 Embryo Protection Act has no provision for research carried out on those embryonic stem cells which have become available abroad under different statutory requirements. Since 2002, the import and use of human embryonic stem cells for research purposes has been regulated by the Stem Cell Act. Even before the Stem Cell Act was passed, a number of relevant institutions, including the German Research Foundation, the German Parliament's Committee of Inquiry on the Law and Ethics of Modern Medicine (14th Legislative Period) and the German Ethics Council, were working intensively on this subject and they also released a number of statements on the issue.

In accordance with the Stem Cell Act (introduced in 2002 and partially revised in 2008), the import and use of embryonic stem cells is generally prohibited and only permissible in certain circumstances. Excepted from the general import and research bans are, among others, those stem cells obtained before the cut-off date of 1 May 2007 (in the original version, the cut-off date was 1 January 2002) and derived from embryos surplus to IVF treatments. Even the passing of the Stem Cell Act has not ended debate on the issue in Germany. 

Further information on present regulations of stem cell research in Germany can be found here: In Focus „Research with Human Embryonic Stem Cells“.

In the Netherlands the creation of embryos for research purposes is forbidden by the Embryos Act. This ban can, however, be lifted by Royal Decree within five years of the Embryos Act coming into force in June 2002, so it is perhaps more appropriate to speak of a moratorium. Were the current ban on research cloning to be lifted, section 11 of the Embryos Act already provides that such research may only be carried out in order to obtain embryonic stem cells for use in transplantations if this cannot be made possible by other means. Irrespective of the above, however, the derivation of stem cells from so-called surplus embryos is currently permitted within the first 14 days of fertilisation provided the donors have given their consent.

In Switzerland, all forms of human cloning, i.e. both for reproductive purposes and in order to obtain human embryonic stem cells for research purposes, are banned. Article 119, Paragraph 2 of the Federal Constitution states: “All forms of cloning and interventions in the genome of human germ cells and embryos are prohibited.” Nevertheless, under certain conditions stem cells may be obtained from surplus embryos or imported for research purposes (See the "In Focus" issue on "Human embryonic stem cell research"). The Stem Cell Research Act (StRA) regulates the conditions under which it is possible to carry out research on human embryonic stem cells in Switzerland. This law is made explicit by the Stem Cell Research Ordinance (SCRO). Both the Act and the Ordinance came into force on 1 March 2005.

United Kingdom
By adopting the Human Fertilisation and Embryology Act (1990), the British legislator permitted the derivation of stem cell from ‘surplus’ embryos created in the context of IVF-treatments as well as the creation of embryos for research purposes. British law is therefore considered to be one of Europe’s most permissive laws in this regard. However, this characterization often neglects that research involving human embryos is restricted to embryos before the 14th day of embryonic development. Furthermore, research is bound by closely monitored regulations and legally defined research purposes. Compliance to these regulations is being supervised by the Human Fertilisation and Embryology Authority (HFEA).

The statutory instrument (2001 No. 188), adopted by the House of commons on 24 January, 2001, amends the Human fertilisation and embryology. Since then, all forms of research on human embryos have to be supervised by the HFEA. Also, the creation of embryos using IVF as well as cloning techniques requires the prior consent of the regulatory agency.

Until 2001 research was restricted to projects aimed at the following purposes:

  • Optimising IFV-methods
  • Increasing knowledge about the reasons for miscarriage
  • Increasing knowledge about the reasons for congenital diseases
  • Improving the effectiveness of methods of contraception
  • Developing methods, allowing to discover chromosomal abnormalities in fertilised oocytes before their implantation (preimplantation genetic diagnosis, PGD)

The 2001 amendment adds three research purposes granting researchers further possibilities to obtain a license:

  • Increasing knowledge about embryonic development
  • Increasing knowledge of severe diseases
  • Transferring new insights into the therapeutic research of severe diseases.

Cloning for reproductive purposes has been banned with the Human Reproductive Cloning Act, 2001. Violation of law can be punished with a prison sentence of up to ten years.

According to the Human Fertilisation and Embryology Act of 2008 and revised by the Human Tissues and Embryos Bill, research on half-human, half-animal chimeras and hybrids as well as their creation are permitted by law under strict conditions.

In the United States, research involving human embryonic stem cells and research cloning is not explicitly regulated on a federal level. Instead, legislative power in this respect is in the hands of the individual states. An explicit regulation of research cloning by law is not provided by all federal states. Furthermore, legal regulations in federal states differ with regard to the derivation and utilisation of human embryonic stem cells. Research cloning is explicitly regulated by law in some federal states like California, where research cloning is permitted, or in North Dakota, where research cloning is prohibited. 

However, public funding of research involving human embryonic stem cells and cloning for research purposes is regulated on the federal level. Until August 2000 no public funding of research on human embryos was available. Even after the introduction of a programme promoting research on human embryonic stem cells by the National Institutes of Health (NIH) and under the support of former US-President Clinton, funding was limited to research on already established stem cell lines derived from surplus embryos originally created solely for reproduction purposes and used with informed consent of the donors. Research projects involving the derivation of stem cells from embryos were still not eligible for public funding. Under President George W. Bush, further restrictions were added. Although federal law did not prohibit private funding of research deriving stem cells from human embryos, public funding was further limited to projects using stem cells lines that had been established before August 2001.

Shortly after his inauguration, this restriction of older stem cells lines concerning federal funding of research involving human embryonic stem cells was overruled by President Barack Obama’s “Executive Order 13505: Removing Barriers to Responsible Scientific Research Involving Human Stem Cells”. This change of course of US-American bio-politics opened an intense public debate in which, above all, members of the Bioethics Council intervened. They had been assigned by former President Bush and were responsible for a restrictive stand towards stem cell research. In June 2009, Obama dissolved the Council and assigned the development of guidelines for public funding to the National Institute of Health (NIH).

On 7 July, 2009, the “2009 Guidelines on Human Stem Cell Research” which had been developed on the basis of the NIHs recommendations, came into force. Research projects involving newer stem cell lines are thus now eligible for public funding. However, funding is restricted to the use of stem cell lines derived from ‘surplus’ embryos left over from IVF-treatments and used with informed consent of the donors.

In 2019, public funding for embryonic stem cell research was restricted under President Donald Trump by prohibiting scientists that were employed by the National Institutes of Health (NIH) from doing research on human fetal tissue derived from voluntary abortions. In addition, an ethics advisory board (The Human Fetal Tissue Research Ethics Advisory Board) was introduced into the NIH approval process for research funding, to be staffed by the US Department of Health and Human Services, which evaluated applications separately. The advisory board stopped its work in September 2020. Furthermore, the restrictions on public funding of stem cell research that were put in place under the presidency of Donald Trump were lifted in 2021 under the presidency of Joe Biden. The other requirements for research projects on embryonic stem cells and their funding remain in place.

Research projects which aim at the creation of human embryos for research purposes, and with this also research aiming at the cloning of human embryos, is still not eligible for public funding.

III. Ethical Aspects

One question which has caused controversy at both national and international level is whether it is legitimate to produce human embryos by cell nuclear transfer for the purpose of obtaining human embryonic stem cells. The protagonists in this debate come from a wide range of relevant scientific disciplines, politics, the public and the media. The discussion is centred less on how legitimate the goals of this research are. The aim of creating immunocompatible organs and researching the differentiation and reprogramming mechanisms in human cells needed for this purpose is generally recognised to be a morally high-ranking research goal. What is controversial here is much more the issue of whether the means of achieving these ends, i.e. cloning human cells, is acceptable and, accordingly, legally and morally permissible - or even advisable.

Therapeutic cloning and research cloning are classed as belonging to the field of consumptive embryo research, i.e. they imply the destruction of the human embryo for research purposes. This problem, already of relevance in the general stem cell research debate, is heightened in the debate on research cloning due to the fact that embryos have to be produced expressly for the purposes of research, i.e. it is not possible, as it is with stem cell research, to use pre-existing non-transferable IVF embryos. Critics of research cloning consider this to be a particularly drastic form of the instrumentalisation of the human embryo. This is rejected by many even if long-term research cloning could lead to producing immunocompatible organs without the need to recourse to embryos.

In this respect, the argument brought against cloning for research purposes is that an embryo produced by nuclear transfer also has, in principle, the potential to develop into a complete organism. In that sense, it would therefore be equal to a traditionally generated embryo in terms of its worthiness for protection. In this context, in ethical discussions, critics refer to the various pertinent arguments used when debating research on human IVF embryos or the permissibility of preimplantation genetic diagnosis: namely, the arguments regarding species affiliation, continuity, identity and potentiality.

The species affiliation argument is based on the premise that every human being is to be accorded the same moral status, or rather, the same right to have its dignity acknowledged simply by virtue of belonging to the 'human' species. The notion that the right to protection or dignity could be coupled to the development of specific human characteristics - for example, certain physical attributes or features of consciousness - is emphatically rejected. Representatives of this side of the argument conclude that insofar as a cloned human embryo belongs to the human species, it must also be considered worthy of protection. 

As part of the continuity argument, proponents point out that the development of an embryo into a 'born' human being is such a continuous process that it is not possible to determine a distinct cut-off point which would justify changing the moral status of a human embryo at a specific point in its development. As a result, the moral status of an early human embryo cannot be measured by degree. Without the possibility of this kind of graduation, the moral status of the embryo must inevitably therefore be regarded as equivalent to that of an adult person.

The identity argument is based on the assumption that fundamentally the identity of a living organism does not change at any point in its development. According to this argument, the identity of a human being over time does not differ in any way from that of the embryo out of which the person developed. This approach too essentially boils down to according a human embryo the same moral status or right to dignity as more developed foetuses or ‘born’ humans.

The potentiality argument, on the other hand, may be summarised as implying that the moral status of an embryo is measured by its capacity to develop into a human subject. This argument points out that unborn or unconscious humans, even though they effectively do not yet, do not currently or no longer possess consciousness or are even able to act autonomously, they should nevertheless be considered as potentially conscious and autonomous subjects. Consequently, according to a variant of this argument's approach, they must therefore be accorded the same dignity as a human being. Thus, this argument maintains that as potential subjects entitled to be accorded dignity, embryos must also be protected on account of their potential capacity for development.

Arguments that refer to species affiliation, continuity, identity or potentiality are countered by those who maintain that ethically appropriate, distinguishing features absolutely exist between early-stage embryos, foetuses and born humans.

Identity or continuity arguments are criticised in the debate chiefly by referring to the different stages of embryonic development. Arguments which refer to the identity of an embryo and that of the person developing from it are criticised on account of the fact that the identity of an embryo in an early stage of development cannot be as clearly determined as some maintain. Proponents of such arguments maintain that it is not until the formation of the primitive streak (i.e. at a later point in embryonic development than the one deemed relevant for research purposes) that a multiple pregnancy can be ruled out and thus the (numerical) identity of the embryo established. They go on to say that at the developmental stage relevant for research projects, embryos do not possess the neural capacity to feel pain, possess consciousness or develop interests of their own and that these abilities are central to attributing full protective rights to embryos. In this context, the arguments which tend to be criticised are chiefly those which maintain that full rights to protection are justified on the grounds that the human embryo belongs to the human species. Proponents maintain that demands for full protective rights for human embryos which refer solely to their affiliation to the human species are insufficiently substantiated unless they refer to the anticipated or pre-existing formation of typically human characteristics. They also go on to say that the species affiliation argument only draws its strength from the fact that members of the human species tend to demonstrate specific features, yet the formation of these features is precluded from the outset in the case of embryos cloned for research purposes.

Accordingly, it is argued that the potentiality argument (based on the fact that an embryo is capable of developing into an agent who possesses consciousness) can at best only legitimise full protective rights for those embryos for whom this potential becomes a reality. The argument continues that since cloned embryos have only been produced for research purposes and not transferred to a uterus and carried to term, potentiality arguments are not relevant to these kinds of embryos, at least. Occasionally in this context, people also point out that those embryos produced using nuclear transfer are not embryos in the conventional sense. They go on to say that in cases of doubt, embryos produced by nuclear transfer should not be accorded the same degree of worthiness of protection as an embryo produced in a conventional way, i.e. by fusing together the nuclei of two germ cells. It is currently the subject of some discussion as to whether the potentiality argument could also come under pressure as current research findings are starting to call into question the concept of totipotency.

Aside from these arguments which refer to the moral status of human embryos, slippery slope arguments also play an important part in the debate. Research cloning opponents point to the technical similarities between therapeutic and reproductive cloning. They assume that the use of cloning techniques for research purposes will open the door to the technology being abused for reproductive cloning. The metaphor of the slippery slope stands for the inexorable nature of certain developments once the floodgates are opened, even if they are only opened ever so slightly. Reproductive cloning is generally rejected by both opponents and proponents of research cloning. The reasons behind this rejection range from concerns over the medical safety of the procedure itself to pointing out that every human being has a right to individuality.

In response to slippery slope arguments, opponents point out that the distinction between therapeutic cloning and reproductive cloning is sufficiently clear. Unlike reproductive cloning, the aim of therapeutic cloning is not that the cloned embryo should develop into a complete organism, nor would it be transferred to a uterus. Rather, the embryo is simply created for the purpose of obtaining stem cells and once these have been harvested, the development of the embryo is curtailed. 

A further objection to research cloning points out that the development, and where applicable the use of this technology in medical practice, requires the availability of a considerable number of female egg cells. Using human egg cells once eggs have been donated is considered to be ethically problematic because on the one hand the hormonal stimulation and puncture required are risky and involve quite considerable difficulties, and on the other hand there is a fear that women could be coerced into donating their eggs for other purposes. Using animal egg cells as an alternative is seen as problematic from an ethical point of view because this could be tantamount to taking the first step towards the formation of chimera or human-animal hybrids. If these were to be used in medical practice, there would be reservations not only regarding their medical safety but also in terms of maintaining strict boundaries between species. 

These experiments with human-animal hybrids and chimeras raise ethical questions in terms of the above-mentioned species argument (i.e. can human-animal hybrids be classified as belonging to the ‘human’ genus?) but also in terms of those moral theories that base the right to protection or dignity on manifestations of specific human characteristics. Human-animal chimeras could potentially develop some of these specific characteristics, i.e. physical features or features of consciousness, thus raising the issue of their moral status.

Relatively little space has been given in the discussion to the objection that the necessity of egg donations could result in undue pressure being placed on potential female donors. Some authors point out that a similar effect has not occurred in donor practices in other fields of medicine, so if the appropriate precautions were taken one could assume that unacceptable pressure would not be exerted on women in the field of egg donation. 

To make an ethical judgement on research cloning, we need to pose the question of whether the procedure is necessary to achieve the objectives and whether the therapeutic approaches pursued are fundamentally valid. It is a matter of intense debate whether the stem cell research required to develop immunocompatible transplants necessarily involves producing human embryos through nuclear transfer or whether stem cells from cord blood or other non-embryonic stem cells such as iPS cells (see module on Reprogramming Cells) could provide an alternative. In this regard, on occasion there are also calls for greater prior verification of the procedure's therapeutic efficacy and efficiency using animal models.

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