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Strasbourg, 29 September 2015DH-BIO (2015) 15
COMMITTEE ON BIOETHICS
(DH-BIO)
Information on the situation regarding the use of CRISPR-Cas9 technology,
in particular with a view to the possible modification of the genetic characteristics of an embryo or germline, in the light of
Article 13 of the Oviedo Convention.
Information provided by delegations
TABLE OF CONTENTS
Genome editing of the human germline is governed by Article 64 of the Genetic Engineering Act (Gentechnikgesetz, Federal Law Gazette No. 510/1994, as last amended by Federal Law Gazette I No. 35/2015) and Article 9 paragraph 3 of the Reproductive Medicine Act (Fortpflanzungsmedizingesetz, Federal Law Gazette No. 275/1992, as last amended by Federal Law Gazette I No. 35/2015). Under these regulations, any genetic modification of the human germline is prohibited.
Austrian Genetic Engineering Act (in German):
https://www.ris.bka.gv.at/GeltendeFassung.wxe?Abfrage=Bundesnormen&Gesetzesnummer=10010826
Austrian Reproductive Medicine Act (in German):
https://www.ris.bka.gv.at/GeltendeFassung.wxe?Abfrage=Bundesnormen&Gesetzesnummer=10003046
According to National Board of Health and the primary sites in Denmark for preimplantation genetic diagnosis, CRISPR-Cas9 is a technology that isn’t used for clinical purposes in Denmark.
The current legislation[1]
Genetic examinations
- Genetic examinations on an embryo are only allowed if there is a known and increased risk that the embryo has a serious hereditary disease.[2]
- Genetic examinations are also allowed to determine or exclude a serious chromosomal abnormality in the embryo.[3] Pregnant women are to meet some specific criteria before this type of examination is performed.
- In connection to assisted reproduction, it is illegal to select the gender of the embryo, unless it happens in order to prevent gender-based hereditary diseases.[4]
Modifications of the genetic embryo
- It is illegal to modify the genetic characteristics of an embryo and use it for assisted reproduction or any other pregnancy.[5]
Scientific experiments
Scientific experiments on embryos and germ lines, which are intended to be used for fertilisation, can only be carried out if the purpose is to:[6]
- improve in vitro-fertilization or other similar techniques that lead to a pregnancy or
- improve genetic examination techniques of an embryo, for the purpose of determining serious hereditary disease or serious chromosomal abnormality or
- acquire new knowledge to exploit new possibilities for the treatment of human diseases.
Scientific experiments are, however, never legal if the purpose is to:[7]
- facilitate the making of hereditary identical human individuals.
- facilitate the making of human individuals by combining genetics from different embryos, before they are inserted into the uterus.
- facilitate the making of a living human individual who is a hybrid with a genome from other species.
- facilitate the development of a human individual in the uterus of another species.
In Germany, the use of CRISPR/Cas9 for altering the genetic information of human germ line cells or of embryos, if the aim is to introduce any modification in the genome of any descendants, would be punishable under Section 5 of the Embryo Protection Act.
Section 5
Artificial alteration of human germ line cells
(1) Whosoever artificially alters the genetic information of a human germ line cell shall be punished with up to five years' imprisonment or a fine.
(2) Likewise anyone shall be punished who uses a human germ cell with artificially altered genetic information for fertilisation.
(3) Any attempt shall be punishable.
(4) Subsection 1 shall not apply to
- the artificial alteration of the genetic information of a germ cell situated outside the body, if any use of it for fertilisation is ruled out,
-
the artificial alteration of the genetic information of any other autologous germ line cell that has been removed from a dead embryo or fetus, a human being or a deceased person, if it is ruled out that
- it will be transferred to an embryo, fetus or human being or
- a germ cell will originate from it, and likewise
- vaccinations, radiation, chemotherapeutic or other treatments which are not intended to alter the genetic information of germ line cells.
According to section 8 (3) germ line cells, for the purpose for this Act, shall be all cells that, in one cell-line, lead from the fertilised egg and sperm cells to the resultant human being an. Further, the egg cell from the insertion of or penetration by the sperm cell until the completion of fertilisation by fusion of the nuclei.
No experimentation on human beings appears to be underway, it is possible that some work is being undertaken on animals.
Italian Law No. 40 of 2004, which regulates medically assisted procreation, even though not explicitly referring to this kind of technique, prohibits the modification of the genetic characteristics of gametes and embryos, except for therapeutic and diagnostic purposes aimed at the protection of health and development of the embryo itself.
Therefore, theoretically, a ‘gene therapy’ on human embryos would not be prohibited, even if implying a modification of the genome, when aimed at treating genetic abnormalities. However, in the current state of scientific knowledge, CRISPR-Cas9 doesn’t offer any guarantee of therapeutic efficacy, which leads us to consider that this technique cannot currently be applied to human gametes or embryos.
Italian Law No. 40 of 2004:
CHAPTER VI – PROTECTION MEASURES FOR EMBRYO
Art. 13 – Experimentation on human embryos
1. Any testing on each human embryo is forbidden.
2. Clinical and experimental research on each human embryo is permitted provided that it only pursues diagnostic and therapeutic purposes related to it, aimed at the protection of the health and development of the embryo itself, and if no alternative methodologies are available.
3. It is, anyway, prohibited:
a) the production of human embryos for research or experimental purposes or for any other purpose than the one provided by this Act;
b) any form of selection for eugenic purposes of embryos and gametes or interventions that, through selection or manipulation techniques, or by means of any artificial process, are intended to alter the genetic heritage of the embryo or gamete or to predetermine its genetic characteristics, except for interventions pursuing diagnostic and therapeutic purposes, as referred to in paragraph 2 of this article;
c) cloning interventions by means of nuclear transfer or early embryo splitting or ectogenesis, for both procreation and research purposes;
d) the fertilization of a human gamete with a gamete of a different species and the production of hybrids or chimeras.
4. Violation of the prohibitions referred to in paragraph 1 shall be punished with imprisonment from two to six years and a fine ranging from 50,000 to 150,000 euros. In case of violation of one of the prohibitions referred to in paragraph 3, the penalty is increased. Mitigating circumstances competing with aggravating circumstances provided for in paragraph 3 shall not be deemed equivalent to or outweighing the latter.
5. Suspension from one to three years from professional practice is provided against a health professional convicted of offences under this article.
Spain ratified the Oviedo Convention on 23 July 1999. The ratification entered into force on January 01 2000.
The Convention for the Protection of Human Rights and Dignity of the Human Being with regard to the Application of Biology and Medicine: Convention on Human Rights and Biomedicine, was opened for signature in Oviedo (Asturias) on 4 April 1997. Relative to intervention on the human genome Article 13 establishes that: “An intervention seeking to modify the human genome may only be undertaken for preventive, diagnostic or therapeutic purposes and only if its aim is not to introduce any modification in the genome of any descendants.”
In accordance with this article we understand that it is not allowed to carry out an intervention to modify the germline only for health care-related purposes.
From an ethical point of view two questions come up. First, the modification of the genome could affect the progeny (the decision of such change can only be taken by the couple), and second, the outcome of this technology is unknown so that the benefits that could be achieved cannot be foreseen.
The use of this technology in research could have a place in the Spanish legislation (Law of Biomedical Research), as long as the embryo were not going to be implanted. In that case possible adverse consequences for the progeny can be excluded. In addition, the application on human and germline of new technology has to be subjected to the observance of some requirements and guarantees of control, among them to have a favorable report of the National Commission of Guarantees of Cells and Human Tissues.
Moreover, since the results of such research could never be applicable in the clinical practice, their possible social benefits would hardly justify the use of human material in its execution.
In the UK, the Human Fertilisation and Embryology (HFE) Act permits the use of new technologies such as gene editing in germ cells, for research purposes, including the use of human embryos up to 14 days old. This is only permitted where the Human Fertilisation and Embryology Authority (HFEA) considers that those activities are necessary for the purpose of the research and where the research is necessary or desirable for one of the purposes set out in the Act, such as to increase knowledge about serious diseases.
The HFE Act only allows the use of eggs, sperm and embryos in treatment that have not had their nuclear or mitochondrial DNA altered. The only exception to this is where eggs or embryos are modified to prevent the transmission of serious mitochondrial disease, but the current regulations permitting this do not allow for the eggs or embryos to be genetically modified.
In September 2015, a group of leading UK research organisations called for a broad and inclusive discussion about genome editing and its future implications. This statement was made in support of the experimental procedure, CRISPR, which is a gene-editing technique that can effect changes to faulty DNA. THE statement also anticipated a possible application to utilise that technology in research initially (but recognising that the law in the UK would need to be changed to allow such techniques in treatment). In April 2015 the Nuffield Council on Bioethics began a project on the ethical issues surrounding genome editing techniques such as CRISPR-Cas9.
In mid-September there was further UK media coverage of this issue, confirming that a UK-based research group have made an initial application to the HFEA for a licence to use the CRISPR technique in a research setting. The HFEA have acknowledged receipt of the application and stated that “Genome editing of embryos for use in treatment is illegal. It has been permissible in research since 2009, as long as the research project meets the criteria in the legislation and it is done under an HFEA licence. We have recently received an application to use CRISPR-Cas9 in one of our licensed research projects, and it will be considered in due course.”
The Government has said publicly that the use of genetically modified sperm, eggs or embryos in treatment is illegal and there are no plans to change this. However, if research that could currently be undertaken under the HFE Act (using altered gametes) could lead to new treatments or therapies that did not require the genetic alteration of sperms or eggs, that would be welcomed.
The Government has also made clear that in introducing regulations to allow mitochondrial donation for the prevention of serious mitochondrial disease, the view was that the mitochondrial donation techniques were not regarded as a form of human genetic modification. The nuclear DNA is not altered and the techniques involve the replacement of mitochondrial DNA not the modification of that DNA.
[1] The consolidation act of assisted reproduction in connection to treatment, diagnostics and scientific experiments etc. nr. 93 off 19/01/2015.
[2] § 7, stk. 1.
[3] § 7, stk. 2.
[4] § 8.
[5] § 27, stk. 1.
[6] § 25.
[7] § 28.