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EMBRYO RESEARCH -

EUROPEAN OVERVIEW

The Dossiers of the European Institute of Bioethics

Stem cells are non-differentiated cells which divide and multiply in their undifferentiated state for a long period. Under certain physiological or experimental conditions, they can also generate more specialized differentiated cells such as nerve cells, muscle cells or insulin producing cells. Stem cells can be divided in three categories:

Totipotent: able to produce every typology of cells of the human organism. (Embryonic stem cells at the stage of zy-gote or blastocyst);

Pluripotent: able to produce every typology

of cells of the human organism but not able to start a new organism. (Embryonic stem cells and iPS cells (Induced Pluripo-tent Stem cells));

Multipotent: able to generate a number of

cell typologies but not every typology. (Adult stem cells, umbilical stem cells, pla-cental and amniotic stem cells, fetal stem cells).

STEM CELLS RESEARCH AND CELL THERAPY

Cell therapy describes the transplant of cells aimed at restoring certain functions of a tissue or an organ that has been modified. Within this framework, adult stem cells are al-ready used for the treatment of :

blood diseases, such as leukemia; wounds and burns; tendons and tissue engineering (such as

the repair of trachea); vessel walls; others are still under evaluation for the

treatment of cerebral motor disabled child and of Krabbe disease.

However, it is believed that the use of pluri-potent stem cells, instead of adult stem cells, would allow to develop more potent treatments. Among pluripotent stem cells there are em-bryonic stem cells and iPS cells (Induced Pluri-potent Stem cells). The latter have been discov-ered by Professor Yamanaka in 2006 and allow obtaining pluripotential cells without destroying human embryos :

This dossier aims to give an overview of the European embryo research framework. Stem cell re-search is one of the most promising areas of biotechnology, offering science the prospect of under-standing cell differentiation and growth, of developing new methodologies to repair or replace dam-aged tissues or cells of the human body, and of understanding diseases development.

One of the possible sources for stem cells are human pre-implantation embryos. Pre-implantation embryos are embryos prior to implantation in the wall of the uterus, created through In Vitro Fertiliza-tion (IVF) – that is the fertilization of an egg by a sperm outside the human body.

When a research involves the use of human embryos it raises ethical questions about limits and conditions for such research.

Different countries have chosen to regulate embryonic stem cell research in very different ways.

SCIENTIFIC ASPECTS OF STEM CELLS

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They are obtained from adult body (i.e. the skin);

They are de-programmed and re-programmed to become non-differentiate;

They can be turned into different typologies of tissues.

Recent studies on animal models have showed that iPS cells can give therapeutic re-sults, as it is the case for embryonic stem cells, such as successful treatment of a myocardial lesion in mice.

Nowadays, human embryonic cells and iPS cells are not used to treat human patients. They are used to categorize diseases and to screen molecules, in order to research for new treat-ments. ADVANTAGES OF EMBRYONIC STEM CELLS AND OF IPS CELLS

Both embryonic stem cells (ESC) and iPS have capacities of reproducing themselves and of differentiating;

Both are useful for the screening of mole-cules and for the creation of examples of diseases;

iPS don’t suffer immune rejection if they come from the patient;

ETHICAL IMPACT OF EMBRYO RESEARCH

Human embryonic stem cell research raises complex ethical questions where scientific pro-gress and hopes has to be balanced with ethical concerns and it has generated a public debate on its guiding ethical principles and limitations. On one hand, there is interest in new knowl-edge that can lead to treatment of incurable dis-eases. On the other, this research involves the use and destruction of human embryos, so it raises the question of ethical values at stake and of the limits and conditions for such research.

The fundamental ethical principles (European Group on Ethics, Opinion n. 15, “Ethical aspects of human stem cell research and use”, 2000) ap-plicable to stem cell research are :

Respect of human dignity; Individual autonomy; Justice and beneficence (with regard to the

improvement and protection of health);

Freedom of research; Proportionality (including that research

methods are necessary to the aims pursued and that no alternative more acceptable methods are available).

As a summary…

It implies the destruction of human embryo; There are alternative ways of research

such as research on animals and on iPS cells which do not imply human embryo de-struction;

It is funding a non-therapeutic research at the expense of a potentially therapeutic re-search;

It is based on the principle that a human embryo can be destroyed in order to obtain material to be used for treating another human being or only as a research pur-pose.

iPS produce pathological models directly from the patient’s cells;

iPS don’t encounter ethical problems.

DISADVANTAGES OF EMBRYONIC STEM CELLS AND OF IPS CELLS

Both can cause cancerous tumors; Both are not currently clinically applied; ESC suffer immune rejection since they

are obtained from the embryo not form the patient; ESC produce only pathological models

limited to genetic diseases; ESC encounter ethical problems since

they imply embryo destruction.

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REGULATION OF STEM CELLS RESEARCH IN EUROPE –

SITUATION PER COUNTRY

EU Member States have taken very different positions regarding the regulation of human em-bryonic stem cell research, according to differ-ent views on what is and what is not ethically defensible. Here are the different positions :

Austria : Stem cell research is regulated by the Reproductive Medicine Act of 2004. Un-der the act, the procurement of cells from a human embryo for research purposes is pro-hibited :

- Embryos cannot be used for any pur pose other than for assisted reproduction; - The use of pluripotent embryonic stem cells that have already been established in a lawful manner (abroad, outside the terri-torial scope of the Reproductive Medicine Act) is permissible.

Belgium : Stem cell research is regulated by the Act regarding Research on Embryos in vitro of 11th May 2003. According to this law, research on embryos within 14 days of fertili-zation is permitted. 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.

Obtaining of new insights in the areas of fer-tility, sterility and organ/tissue transplantation also constitutes grounds for conducting re-search on embryos in vitro, if no other re-search 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. According to the Law on research on human embryos in vitro of 2003 it is permitted :

- to obtain human embryo stem cells from supernumerary IVF embryos;

- to create human embryos for research, including somatic cell nuclear transfer (SCNT)2.

Biotechnology is an area with strong poten-tial economic growth and welfare creation. Stem cell research plays a part in its develop-ment. Although considerable funds are avail-able for investment in stem cell research, com-mercial returns on such investments are for the moment very modest, due to the limited results obtained in clinical trials or on animal models.

Another possible limitation that is thought to affect stem cell research and commercializa-tion of therapies based on stem cells is the pat-entability of human stem cells. On one hand, patent rights are necessary to protect and en-sure substantial investments in the sector to support research and innovative development. On the other hand, academic research is stimulated by free and open access to these cell lines, since starting materials are essential for their research.

According to the European Court of Justice, research based on the use and destruction of human embryos are not patentable.

The use of human embryos for industrial or commercial purposes has been banned as im-moral and the use of human embryos restricted to scientific research purposes is not pat-entable, as granted patents must be suscepti-ble of industrial application. A “human embryo” within the meaning of Union law is any human ovum after fertilization or any human ovum not fertilized but which, through the effect of the technique used to ob-tain it, is capable of commencing the process of development of a human being. The judgment says : “it has to be excluded from patentability any procedure that implies the destruction of the human embryo by taking stem cells from a human embryo at the stage of blastocyst”1.

SOCIO-ECONOMIC IMPACT OF EMBRYO RESEARCH

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Finland : The medical research Act of 1999 covers the preconditions and use of human embryos up to 14 days of embryonic devel-opment. The production of human embryonic stem cells from supernumerary embryos is allowed.

France : Laws on Bioethics (1994, 2004, 2011) have multiplied their derogations to the principle of respect of human life. Today, these laws have adapted to the transgres-sions made possible by technology. These laws don’t protect the human embryo.

- “Research on human embryo is banned”; “A human embryo cannot be designed nor created through cloning, nor used for comerc ia l and indust r ia l pur -poses” (Bioethics law of 2004); - Research on “embryonic stem cells and stem cells lineages are banned”; “For derogation […] research is authorized if the following conditions are encountered : […]; research can allow improved medical progresses; it’s clearly established that it’s impossible to get results expected from research if human embryos, embryonic stem cells or stem cells lineages are used” (Bioethics law of 2011). The law of 2004 has required “improved therapeutic progresses” in order to dero-gate the ban. The law of 2011 encounters that condition and embryo research is permitted under that law.

Germany : The use of embryos for research is heavily restricted in Germany under the Embryo Protection Act of 1991.

- The embryo is also protected under the German Constitution. The Basic Law states that: “human dignity is inviolable” and that “everyone has the right to life and inviolability of his person”; - German law gives priority to adult stem cells under the 2002 Stem Cell Act, but the importation of embryonic stem cell lines into Germany is permitted under strict conditions approved by the German parliament; - Embryonic stem cell lines can only be used for research if they are vital in devel-oping new medical and scientific knowl-edge.

Greece : Article 1459 of Law 3089/2002 on medically assisted human reproduction allows the use of surplus reproductive material for research, subject to the consent of the donors. Embryos can be frozen and stored for up to five years, after which they must either be de-stroyed or used for therapeutic or research pur-poses. Fertilized eggs that have not been fro-zen have to be destroyed 14 days after fertilization. Italy : Stem cell research in Italy is regulated by the Law 40 (19 February 2004).

- The embryo is recognized as a subject of rights from the moment of fertilization; - The law prohibits the use of embryos for any research unless it is specifically aimed towards improving the therapeutic and medical condition of the embryo concerned; - Law 40 gives support to (adult) stem cell research. It is estimated that around 30,000 supernumerary embryos have been stored prior to the introduction of this Law.

Netherlands : Stem cell research in the Netherlands is regulated by the 2002 Embryos Act. Research was previously permitted, al-though the rules needed amendment.

Whilst the Embryos Act prohibits the creation of embryos for research purposes, research on human embryonic stem cells is permitted. To this purpose stem cells may be obtained from supernumerary embryos up to 14 days after fertilization and with the parents’ prior consent. Such derivation of stem cells and also their use for research require the authorization of the regulatory agency, the Central Committee for Research Involving Human Subjects.

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Spain : Spanish government has a compre-hensive regulatory framework for stem cell re-search, with a series of laws and regulations applied to different aspects of research.

- The Law on Biomedical Research (Law 14/2007) allows for research on embryos for therapeutic and research purposes;

- The creation of embryos specifically for re-search is prohibited;

- The act also regulates stem cell trials and other research involving humans (except clinical trials) and their biological samples, as well as the donation and use of embryos, cells, tissues and organs.

Sweden : the Activities Involving Human Eggs for Research or Treatment Purposes Act of 1991 allows for research on embryos for up to 14 days after fertilization and their destruction afterwards.

- The Bio-banks in Medical Care Act of 2002 set up a national stem cell bank; - The 2005 Act on Genetic Integrity allows the creation of human embryos for research using somatic cell nuclear transfer (SCNT): “therapeutic cloning”. This technique can be used only following approval by an ethics committee and by donors.

United Kingdom : legislation allows the de-struction of embryos for extracting human em-bryonic stem cells, only for one of the following reasons :

- For increasing the knowledge on the development of embryos;

- For increasing knowledge on serious diseases, like Alzheimer or Parkinson;

- To increase knowledge on applying developing treatments for serious diseases.

Embryonic stem cell research is allowed subject to a license from the Human Fertiliza-tion and Embryology Authority (HFEA). Li-censed research can only take place on em-bryos up to 14 days. Stem cells are taken from the blastocyst at the 5th or 6th day. Licensed research can only take place on embryos created in vitro. Most embryos used in UK stem cell research are embryos initially cre-ated for use in fertility treatment, but not used. These supernumerary IVF embryos, if donated with the full consent of the parents, can be used for research. A 2008 amendment allowed the HFEA the power to grant licenses to add limited amounts of animal cells to human ones to make hybrids such as true chimeras, true hybrids and trans-genic human embryos.

Note :

1- Brüstle v/ Greepeace, 18 October 2011. 2- SCNT involves replacing an egg’s nucleus with

the nucleus of the adult cell to be cloned (or from an embryo or foetus) and then activating the egg’s fur-ther development without fertilisation. The egg ge-netically reprograms the transferred nucleus, ena-bling it to direct development of a whole new organism.

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Commission of the European Communities, Report on Human Embryonic Stem Cell Research, Bruxelles, 2003. Deutsches Referenzzentrum für Ethik in den Biowissenschaften, Selected National and Interna-tional Laws and Regulations in Stem cell research, www.drze.de Fazzini, A., Burkey, B., Munoz, D., Yang, R., The Economics of Embryonic Stem Cell Research in the United States, Focus, Carnegie Mellon University, 2007. Fondation Jérôme Lejeune, Manuel Bioéthique de Jeunes, Galiote-Prenant, Vitry-sur-Seine, 2012. International Consortium of Stem Cell Networks, Global Regulation of Human Embryonic Stem Cell Research and Oocyte Donation, www.stemcellconsortium.org Lafont, H., La bioéthique, Ed. La Nef, 2001. Pessina, A., Bioetica. L’uomo sperimentale, Mondadori, Milano, 2006. Regulation of Stem Cell research in Europe, www.eurostemcell.org Service Public Federal Santé Publique, securité de la chaîne alimentaire et environnement, Loi relative à la recherche sur les embryons in vitro, 2003, http://www.ejustice.just.fgov.be/cgi/article.pl Stem Cell Laws, www.stemcellsfreak.com Stem Cell Research-Pros and Cons, www.experiment-resources.com, 2011.

Dossier réalisé par LAURA GOTTI TEDESCHI

www.ieb-eib.org 1 rue de la Pépinière—1000 Bruxelles

BIBLIOGRAPHY