1. International Documents
At the international level, many texts proclaim the right to life in general, e.g. the Universal Declaration of Human Rights of 1948 in its Art. 3 or the International Covenant on Civil and Political Rights of 1966 in its Art. 1. Controversially discussed is whether the documents apply to embryos.
The Council of Europe’s Convention for the Protection of Human Rights and Dignity of the Human Being with regard to the Application of Biology and Medicine of 1997 leaves each country the responsibility for legislating on the permissibility of embryo research. The Convention is not ratified by all European member states 1 – for example Germany, the United Kingdom, Ireland and Austria did not ratify it.Reference Druml 2 On the one hand, Germany and Ireland did not sign the convention as for them it is not concrete enough, and on the other hand the United Kingdom did not ratify it because it is too restrictive from a British point of view (Ref. Reference Druml2, p. 651). This shows the completely different views on this very ethically debated topic. The Convention only stipulates two conditions in Art. 18 – the prohibition of producing human embryos for research purposes and the adoption of rules designed to assure adequate protection for the embryo. The second condition leads to the unsolved question of what is an ‘adequate protection for the embryo’ which is not defined further in any document.
Furthermore, the Charter of Fundamental Rights of the European Union expressly prohibits reproductive cloning in its Art.3, but does not comment explicitly on embryo research. In a non-binding resolution on 7 September 2000, the European Parliament stated its opposition to the creation of supernumerary embryos and to therapeutic cloning.
The European Group on Ethics in Science and New Technologies of the European Commission (EGE) adopted Opinion No. 15 of 2000 on the ethical aspects of human stem cell research. The Group stated the importance of different opinions and ethics by saying that ‘pluralism is characteristic of the European Union, mirroring the richness of its tradition and adding a need for mutual respect and tolerance. Respect for different philosophical, moral or legal approaches and for diverse cultures is implicit in the ethical dimension of building a democratic European society’. The Group consequently stated that ‘in the context of European pluralism it is up to each Member State to forbid or authorize embryo research’. The Group outlined that if the research is permitted it should be under ‘a strict public control by a centralized authority.’ Moreover, EGE considered the creation of embryos with donated gametes for the purpose of deriving stem cells as ‘ethically unacceptable’.
2. National Legislation
The European countries have chosen various ways to deal with the allowance of research with supernumerary embryos and the derivation of HESC from supernumerary embryos. For instance, France, Spain, Portugal, the Netherlands, Denmark, Norway, Finland, Estonia, Slovenia, Hungary, Czech Republic and Greece allow the research. France modified its statute concerning stem cell research and now allows it under special circumstances. 3 The regulations in the United Kingdom, Belgium and Sweden are even more liberal. They allow the production of embryos for research purposes. The United Kingdom and Belgium allow the derivation of stem cells from embryos created by nuclear transfer, which in fact means therapeutic cloning. 4 Recently, a new discussion started in the UK as a scientist asked for permission to create a hybrid embryo.Reference Trips-Hebert 5 Austria does not restrict the importation of HESC or their utilization at all.
In contrast, there are also more restrictive regulations in some member states. In Poland, Lithuania and Slovakia research with HESC is completely forbidden whereas in Germany, Italy and Ireland research with imported HESC is allowed under very strict circumstances.
Consequently, the European Union does not want to create a binding opinion for this topic as there is, in no way, a consensus between all member states. There are different ethical standards and solutions of how to deal with supernumerary embryos and when an embryo is protected by human dignity. For instance, within the German Embryo Protection Act, the term ‘embryo’ is defined as the human egg cell, fertilized and capable of developing, from the time of fusion of the nuclei, and further, each totipotent cell removed from an embryo that is assumed to be able to divide and to develop into an individual under the appropriate conditions. On this basis, many authors bestow human dignity on the entity as soon as the gametes fuse to form a zygote. This shows that the German standard is set very high. On the contrary, the underlying principle of the British Human Fertilization and Embryology Act 2008 is that an embryo is covered by human dignity at a later point in time (after 14 days), therefore the creation and utilization of embryos until this point is allowed.Reference Haimes, Porz, Scully and Rehmann-Sutter 6
3. National Differences: a Curse or a Blessing?
The question that arises is what lessons can be learned from the various legal positions. First of all, different legal positions are an expression of national sovereignty and due to this are not to be considered as negative. All countries in Europe have their own culture and moral standards and therefore different opinions and legal positions. It is important to cherish these differences and promote an open-minded discussion in the countries to include the society in the process. This is in accordance with the European Law as there is no unified regulation.
The differences as such do not constitute a good reason for a change in their own country’s legislation and especially should not start a ‘race to the bottom’ towards unrestricted research. But legislators are well advised to observe foreign experiences very carefully since the discrepancy between jurisdictions is like an in vivo experiment which can remove or confirm fears and hopes. The prospects of research with HESC are still a matter of speculation. The proponents hope to find cures for incurable diseases such as Parkinson’s, Huntington disease, and so on, and to understand the causes of birth defects, infertility and pregnancy loss (Ref. 4, p. 8). The opponents are in fear of an instrumentalization of human embryos and the decrease of moral standards regarding the embryo and its dignity. 7 It is the duty of all countries and their legislators to examine their standards closely and be well aware of the changes and the discussion in their own and other countries.
In any case, legislators have to ensure a legal system without inherent contradictions to prevent scientists and society from insecurities about the relevant legislation and its consequences.
4. The Legal Situation in Germany
4.1. Introduction
In Germany, two different Acts are relevant for the allowance of research with HESC – the Embryo Protection Act from 1990 and the Stem Cell Act from 2002. Research with induced pluripotent stem cells (iPSC) as such is not subject to specific regulations in Germany; however, in Sec. 5 Embryo Protection Act it is stated that it is forbidden to use artificially altered germ cells for fertilization; this includes artificially created egg and sperm cells from iPSC. 8
According to the Embryo Protection Act (EPA) the use of an embryo for a purpose not serving its preservation is forbidden (Sec. 2 [1]). Consequently the derivation (production) of human embryonic stem cells (HESC) and with it the destruction of embryos is prohibited in Germany.
The Stem Cell Act (SCA) has been a political compromise between those who wanted to prohibit research with HESC entirely due to the human dignity of embryos and those who wanted to leave the door open in the hope of finding therapies for still incurable diseases. The act was the outcome of a strongly controversial discussion about moral standards and freedom of science. By prohibiting the derivation of human embryonic stem cells while granting exemptions for research with human embryonic stem cells, the German legislation has made an important contribution to social pacification which has existed for quite some time.
Section 1 of the SAC states:
In consideration of the State’s obligation to respect and protect human dignity and the right to life and to guarantee the freedom of research, the purpose of the presented Act is 1. to ban, as a matter of principle, the importation and utilization of embryonic stem cells, 2. to prevent demand in Germany from causing the derivation of embryonic stem cells or the production of embryos with the aim of deriving embryonic stem cells, and 3. to determine the requirements for permitting, as an exception, the importation and utilization of embryonic stem cells for research purposes.
According to Sec. 4 (1) of the Stem Cell Act, the importation and utilization of embryonic stem cells is prohibited. Section 4 (2) permits research if it is approved by the competent agency, the Robert Koch Institute. This approval depends on four criteria which are laid down in Sections 4 and 5 of the Stem Cell Act. Therefore, the exception of the ‘fruits of the poisonous tree’ doctrine and with it the allowance of the use of its fruits is very strictly limited. The criteria on which the approval depends are the following:
(a) Cut-off date: The stem cells must have been derived and kept in culture before 1 January 2002/1 May 2007 in accordance with relevant national legislation in the foreign country where they have been produced. This condition is called the ‘cut-off date’.
(b) Origin of the stem cells. The embryos from which the stem cells have been derived must have been produced by medically-assisted in vitro fertilization in order to induce pregnancy and must definitely no longer be used for this purpose. It must be evident that this is not due to inherent reasons in the embryos themselves. Moreover, no compensation or other benefit in money’s worth has been granted or promised for the donation of embryos for the purpose of stem cell derivation.
(c) Intended utilization of the cells: Research is only allowed for high-level goals without any alternative. Furthermore, the Central Ethics Commission for Stem Cell research as an independent, interdisciplinary committee has to express an opinion about the utilization.
(d) Uniformity of the legal system: Other legal provisions, in particular those of the German Embryo Protection Act, shall not conflict with the importation or utilization of the embryonic stem cells.
4.2. Double Moral Standards?
It has been pointed out that the derivation (production) of embryonic stem cells is forbidden in Germany. However, the importation and utilization is allowed if it is permitted by the competent agency. Does this lead to double moral standards in German legislation?
This question definitely has to be answered in the negative as there are legal and moral differences between an original act and following acts of exploitation. The state’s legal system is not responsible for the protection of legal interests situated abroad in the same way as it is for those within the country.Reference Kloepfer 9 At most there might be a responsibility to prevent embryos from being consumed for ‘German research’ or on behalf of German scientists. Moral objections to the exploitation of embryonic stem cells do not per se exclude any weighing of interests. Moreover, the legislator has to take into consideration the freedom of science and his/her responsibility for ill people. The responsibility for preventing the consumption on German behalf and regarding the scientists and the ill who depend on such specific research must outweigh the moral objections.
The consumption of embryos in the past is irreversible. The former embryo is no longer protected by Art. 1 of the German constitution,Reference Dederer 10 even though the application of Art. 1 of the German constitution for living embryos is debated. It is discussed if a post-mortal protection of the human dignity of the embryo is possible.Reference Brewe 11 Even if a post-mortal protection of human dignity is possible for an embryo (see below), it is open for weighting with other constitutional rights. (Ref. Reference Dederer10, p. 309) As stated above, the legislator must pay particular attention to the rights of the ill and consider the possibility that HESC research might find cures for serious diseases.
The Stem Cell Act inhibits German participation in the derivation of embryos situated abroad by fixing the cut-off day to an earlier date than the date when the act came into force. The original Act came into force on 1 July 2002 and according to this original Act the stem cell must have been derived and kept in culture before 1 January 2002. An amendment which shifted the cut-off date to 1 May 2007 came into force on 21 August 2008.
4.3. The Cut-off Date
Benefit of the cut-off date?
A heated discussion arose about the concept of the cut-off date. The object of this restriction was to protect embryos from abroad of being utilized for the purpose of German research. The legislator wanted to prevent the destruction of embryos on behalf of German scientists. Some proponents of the cut-off date consider it as the greatest possible protection of life.Reference Fassbender 12 But the consequences of the cut-off date are far-reaching and are based on the general suspicion that all destructions of embryos in order to derive embryonic stem cells after the cut-off date have been ordered by German researchers and are not based on the individual behaviour of a scientist acting abroad. The restriction is too far-reaching as any German participation in the derivation of embryonic stem cell is already considered illegal apart from the Stem Cell Act. The German Embryo Protection Act in connection with the general rules of criminal law prohibits any participation even if the derivation of stem cells is legal at the respective place.
Moreover, the aim of protecting international embryos from being utilized for the purpose of German research is not achieved by this restriction due to the increasing global demand for embryonic stem cells. The existing cell lines can be kept in culture for a long time and can be propagated at will. For this reason, a connection between the number of embryonic stem cells used in Germany and the number of embryos destroyed abroad is (at the least) extremely questionable.Reference Klopfer 13 Consequently the cut-off date does not fulfil its aims.
Additionally, the constitutionality of the cut-off date is very questionable as the freedom of science, which is granted in Art. 5 of the German constitution, is affected. Freedom of science guarantees not only the freedom to choose the topic of the research but also the freedom to choose the necessary means for the research.Reference Spickhoff 14 In general, the only reason to restrict a constitutional right is the protection of another (conflicting) constitutional right. Embryonic stem cells are not considered as an embryo and as such they are not an object of Art. 1 of the German constitution, which grants human dignity 15 (Ref. Reference Spickhoff14, p. 2794). Other authors create a protection of the embryonic stem cells by means of post-mortal protection of human dignity.Reference Dederer 16 This does not seem to be highly consistent as the embryo situated abroad was never a legal subject and an object of the German Constitution. Thus, its protection is not of concern to the German legislation (Ref. Reference Spickhoff14, p. 2790). Furthermore, even though the concept of post-mortem protection of human dignity is recognized by the Federal Constitutional Court in general, this protection is linked to the fact that the person in question lived and worked in a human community and therefore its respectful memories are protected even after death. This idea cannot be transferred to embryos in vitro.
Postponement of the cut-off date
The act came under a lot of pressure as the effects of the original cut-off date increasingly tended towards a complete prohibition of research. This was due to the fact that there had been massive improvements of the quality of the HESC. The ‘old’ HESC were of considerably inferior quality as they were cultivated on layers of animal cells and thus could not be used therapeutically due to a serious risk of infection for human beings. Moreover, the stem cell lines were not isolated and cultivated under standardized conditions pursuant to the rules of good laboratory practice or good manufacturing practice. Further, sub-optimal culturing conditions have in part resulted in genetic and epigenetic changes. The expression patterns and development stages of the old stem cell lines were very heterogeneous. The cut-off date provision resulted in considerable problems within international cooperation as there was an extremely high risk that criminal offences would be committed by German or foreign researchers in collaborative projects where work was undertaken with ‘new’ stem cells. A large number of opinions and reports referred insistently to the problem of an increasing international isolation of German researchers.Reference Taupitz 17 The German parliament was well aware of these issues and in April 2008 it was therefore decided to shift the date to 1 May 2007. 18 After the amendment of the Stem Cell Act it is noticeable that not only did the requests of using HESC (and the approvals) increase remarkably, but so did the amount of scientific publications. 19 The change of the cut-off date obviously had the desired effect and German research seems to continue to reinforce its position.
4.4. Origin of Stem Cells
The permission to import HESC further depends on, inter alia, the origin of the stem cells. The embryos from which the stem cells have been derived must have been produced by medically-assisted in vitro fertilization in order to induce pregnancy and were definitely no longer used for this purpose and there is no evidence that this was due to reasons inherent in the embryos themselves. This ensures the impossibility of the embryo’s future survival.
The rationale of the criterion is that apparently performing a pre-implantation genetic diagnosis (PGD) and the utilization of embryos that have been selected after a PGD was an indictable offence. Therefore, German researchers should not profit from such an offence. Consequently, research with stem cells that have a defined genetic defect is prohibited, even though these cells would be very useful to generate scientific knowledge about the defect. Precisely such research would be desirable, not least in pharmacogenetics or toxicity testing, as it avoids endangerment to patients. The risk for patients decreases since these cells make it possible to test new medical products in in vitro conditions before being used on human beings.
In contrast to the background of the Stem Cell Act, pre-implantation genetic diagnosis (PGD) is allowed under strict circumstances in Germany according to Art. 3a Embryo Protection Act since 2011. This means that performing PGD is apparently no longer an indictable offence. The legislator allowed the PGD for women or couples if the genetic pre-disposition suggests that their offspring will be highly likely to have serious genetic injuries.
The question arises of whether the use of embryos for research purposes is really a violation of human dignity. The embryo, which was rejected from the genetic mother after a PGD because of inherent diseases, has no chance to be transferred to any woman. It does not have an opportunity of survival as there is no obligation to keep the supernumerary embryos alive.Reference Günther, Taupitz and Kaiser 20 It is questionable whether the disposal constitutes a violation of human dignity solely because the embryos are not merely disposed of, but additionally used to derive stem cells. This can hardly be seen as a ‘scornful disparagement’ according to the judicature of the Federal Constitutional Court. It is no longer consistent that the legislator does not allow the importation and utilization of HESC, which were selected after a PGD as the former reason is eliminated and the PGD is legal in Germany. There seems to be no legal or ethical difference between the two types of embryos except for the scientific advantages. Consequently, there is an inherent contradiction within the German legal system.
4.5. Intended Utilization of Stem Cells
Lack of alternatives
As stated above, the permission to import HESC depends on the intended utilization in Germany. They may be imported and used only for research that serves eminent research aims to generate scientific knowledge in basic research or to increase medical knowledge for the development of diagnostic, preventive or therapeutic methods for the cure of severe and incurable diseases. The severity of an illness is assessed by its impact on the life and health of the affected person (Ref. Reference Spickhoff14, p. 2795). Deadly diseases or such which cause disability are, by definition, severe illnesses. Huntington’s and Parkinson’s are examples of severe diseases (Ref. Reference Spickhoff14, p. 2795).
Furthermore, in the application process it has to be shown that, according to the state-of-the-art of science and technology, the questions to be studied in the research project have been clarified through in vitro models using animal cells or experiments as far as possible. Additionally, it has to be proven that the scientific knowledge to be obtained from the research project will only be achieved by using embryonic stem cells.
Both partial requirements from Sec. 5 of the Stem Cell Act may be reduced to the linked aspects of necessity and subsidiarity, and can be summarized under the term ‘lack of alternatives’ (Ref. Reference Brewe11, p. 200). The constitutionality of this criterion is also debated as, if a post-mortal protection of the embryo is denied, the freedom of science is restricted by the legislator without another constitutional right.Reference Taupitz 21
The reason why this criterion was implied is that embryos and HESC are valuable and ethically controversial resources. Therefore, they should only be used for high-ranking goals. Consequently, an exemption of the ‘fruit of the poisonous tree’ doctrine is made for research purposes. Generally the consumption of embryos is forbidden in Germany and ethically rejected (see above). With the allowance of the importation of embryonic stem cells for research purposes, the legislator creates an exemption to support scientific development and to ensure the freedom of science.
Research purposes
On the one hand, approval requires a high-ranking goal but on the other it prohibits the application of stem cell therapies in daily clinical practice. The embryonic stem cells are only allowed to be used for research purposes. Research purposes cover both basic research and the transfer to the human body for a therapeutic experiment (Ref. Reference Spickhoff14, p. 2796). However, the main long-term goal of the research of HESC is to find a cure for incurable illnesses, which is definitely a high-ranking goal. Thus, the research should end in clinical practice for the ill. Nevertheless, according to the current Stem Cell Act this is not allowed as the requirement of research is not met. The allowance for research purposes only, on the one hand, and the high-ranking goal of curing the ill on the other seems to be an inherent contradiction in the German legal system.
5. Closing Remarks
There is a good chance that the act will be repeatedly challenged (see above) if stem cell therapy becomes available for daily clinical practice. The number of international projects in which therapeutic experiments are used has increased in the last four years. 22 There were great successes with studies in the US where scientists tested a procedure to cure an illness of the eye (Morbus Stargardt) (Ref. 22, p. 12). Nevertheless, there is still a long way to go before stem cell therapy may be available for daily clinical practice. If, on the contrary, the future should prove that the concept of stem cell therapy is a fallacy, then Germany will not have dirtied its hands.
Acknowledgements
I would like to express my thanks to my assistant Anna Grümmer for her support to this article.
Jochen Taupitz is Professor of Civil Law, Law of Civil Procedure, Private International Law and Comparative Law at the University of Mannheim. He is Managing Director of the Institute for German, European and International Medical Law, Public Health Law and Bioethics of the Universities of Heidelberg and Mannheim. Since 2001 he has been a member of the German Ethics Council and of the former National Ethics Council. He is a member of the Academia Europaea and of the (German) National Academy of Sciences Leopoldina.
