Human Genetics Commission

Information Gathering Session on Stem Cell Research:

Joint Meeting between Eurostem and the Human Genetics Commission

13 May 2002

Introduction

HGC Member Prof John Harris co-ordinates the Eurostem project, which aims to develop an ethical framework for stem cell research and to monitor public reaction towards it in Europe. Prof Harris arranged a meeting between HGC and Eurostem during the former’s visit to Manchester in May 2002.

Five Eurostem members gave presentations, and each presentation was followed by a

short discussion.

Key points raised in presentations

Tissue Storage and Retention

Professor Margot Brazier, Chair of Retained Organs Commission

University of Manchester

Regulation of the use of human tissue

  • There are numerous uses to which human tissue can be put; for exampletransplantation, therapy, reproductive cloning. This makes it difficult to effectively regulate the retention and use of tissue; however, transparency of the process, and the public trust so engendered, are important in allowing research to progress.
  • The Retained Organs Commission (ROC) was established after revelations at the Royal Liverpool Children’s Hospital at Alder Hey and at the Bristol Royal Infirmary that organs and small tissue blocks were taken without consent from children in autopsy; particular concern was excited by the removal of reproductive organ tissue. Tissue samples should only be retained within a distinct framework of regulation underpinned by clear principles.
  • ROC have recommended that post-mortem tissue be regulated, but what about surgical waste? Should ‘tissue’ encompass cell-regenerating material and body fluids? What does respectful disposition of post-mortem material entail? Who has authority over the reproductive material of someone who had given consent for her sample to be used in post-menopausal HRT research but died before her menopause occurred?
  • How can use of human tissue be feasibly regulated?

Transparency and trust

  • One common perception is that public opinion is misinformed and emotional, and the media does not always facilitate understanding. There can be a basic failure of communication between doctors/nurses and patients/relatives, eg parents of deceased children may not be informed that their consent is required for removal of tissue. Doctors may be reluctant to explain as they do not want to worry already distressed parents. However, there may be ethical or cultural objections to the removal of even a few cells.
  • Dame Nora O’Neill in her 2002 Reith lecture series on trust and accountability commented that while regulation was designed to indicate to the public that the Government was in control, increasingly was being interpreted as indicating that a situation was not right or was being covered up. Thus extending regulation, even if justified, could paradoxically generate further mistrust. But if a system which engendered strong public confidence could be created, then people would be willing to donate tissue, for example, to a stem cell bank.
  • The value attached to dead body tissue is demonstrated by the elaborate rituals surrounding death such as funerals and cremations, and the mutilation of a body in death is often seen as the mutilation of the person. Language related to body parts also equally relates to the person.

Discussion

  • An element of flexibility is required in any regulatory framework governing the use of human tissue. A ‘tickbox’ approach would do nothing to engender trust; instead broad principles must be developed, adherence to which would induce public confidence.
  • Public perception of scientists and doctors are different; at ROC meetings there is a different reaction to medical as opposed to non-medical scientists. The general view of doctors is that they are either very good or very bad, but there is a general fear of biological scientists who are felt to be working on hidden research agendas.
HFEA Licensing and Patient Recruitment: Realities and Fairness

Professor Peter Braude

King’s College London

Types and sources of stem cells

  • There are three types of stem cells:

Multipotent, able to produce many specialised cell types; most adult stem cells are multipotent;

Pluripotent, able to give rise of all cell types except extra-embryonic tissue; obtained from embryonic stem cells;

Totipotent, able to produce entire organisms; obtained from blastomeres.

  • Human embryonic germ cells, or EG cells, have been obtained from 5-8 week old fetuses aborted for therapeutic reasons. Another source of stem cells could be from parthogenetically-derived oocytes, ie there is no paternal contribution.
  • Human embryonic stem cells (ES cells) can be derived from cleavage stage human embryos donated as surplus to human fertility treatment. Theoretically immunologically tolerated stem cells should also be derived using the technique of cell nuclear replacement (CNR) in human oocytes.

Relevant legislation

  • Under terms of the Human Fertilisation and Embryology Act 1990, research using human embryos can only be carried out under license from the Human Fertilisation and Embryology Authority (HFEA). Research may only be allowed of deemed necessary and desirable, and for strictly defined purposes. Whole embryos may not be grown in vitro beyond 14 days although stem cells derived from embryos disaggregated before this time may. Parthenogenetically created blastocysts are not embryos under the terms of the Act, as they are not derived from fertilisation.
  • Information important to the HFEA in its decision making about granting a licence includes: the source and disposal of the embryos; how audit and consent procedures are managed; distribution of embryos between research and treatment; whether the centre is adhering to the scope of the project originally granted. By August 2001, three stem cell licences that involved the use of embryonic stem cells had been granted, all under the terms of the original legislation.
  • The report from the House of Lords Select Committee, published in March 2000, amongst many recommendations, approved the ethical derivation of stem cell lines from human embryos, and recommended that further research should be carried out. It recommended that embryos should not be created specifically for research unless there was exceptional need that could not be met by the use of surplus embryos. CNR was permitted (but not for reproductive cloning) and should be regulated by HFEA, and consideration should be given to the setting up an UK stem cell bank.

Practical considerations

  • The following requirements should be met:-

Those obtaining stem cells for research should be separate from those using them;

Fully informed consent should be obtained for the use of embryos and eventual use of stem cells;

It should be possible for consent to be withdrawn;

Considerations of possible therapeutic use should be realistic;

Stem cells created for therapy will need to conform to Tissue Banking Regulations, unlike those created for research

The source of the cells should be known as traceability is a key issue in good manufacturing practice.

Discussion

  • Research carried out in an animal model, even a primate one, is only an approximation to the human situation; even if a therapy works in chimpanzees, it does not automatically imply that it could be used for the treatment of humans.
  • One view of donors not benefitting financially from treatment developed using their tissue is that this is state-assisted robbery – it was an interesting question. The subject of commercial applications, which had been raised in the House of Lords report, was very pertinent to future development, and means of regulation would need to be considered.
The Status of Stem Cell Research in Germany

Professor Dr. Ludger Honnefelder

Institut für Wissenschaft und Ethik, Bonn

Ethical considerations

  • The broader debate in Germany started in November in 1998 with the cultivation of human embryonic stem (ES) cell lines in the USA (Note1). The main considerations are to what extent medical research is dependent on ES cells, and what level of protection should be afforded to the human embryo. There are two basic positions on the latter question: the restrictive position which acknowledges the human dignity of the embryo at a very early stage of development, and the gradualist position which acknowledges that full human dignity is achieved only when the embryo has reached a certain stage of development.
  • The Basic Law, the fundamental ethical regulations underlying the German constitution, guarantees the freedom of research and science from political and social restrictions. Research can only be restricted if it conflicts with other constitutional guarantees, such as the right to life and inviolability of the person (Note 2). The aim to find treatments for, or ways to prevent, disease has high moral ranking, but what ranking should be afforded to an early embryo, which can be destroyed in the process of obtaining stem cells?
  • Consideration of whether or not human ES cells should be used needs to take into account the mode of generating the embryos from which the ES cells will be isolated. The technique of cell nuclear replacement is considered by some to raise large ethical issues as it involves generating an embryo for research/treatment purposes only and also predetermines an embryo’s genetic identity. Some feel that such considerations do not apply to surplus embryos as these do not have the prospect of becoming humans, and therefore their use would not violate the notion of human dignity.
  • The ethical debate centres on whether there is a moral difference between the isolation of human ES cells and their subsequent utilisation. The public debate is intense; a recent survey of 1,000 people revealed that the vast majority of were critical of embryo research of any kind or of importing and using of human ES cells.

Developments in Germany

  • In March 1999 the German Science Foundation (DFG), the major German research foundation, released a statement that human embryonic stem (ES) cells should not be used regardless of how they were derived since they came from cells which were capable of becoming a fully developed human being. Embryonic germ (EG) cells were better candidates for research as they raised less ethical issues. There was no need to change the law, particularly with the Embryo Protection Act already in place (Note3).
  • The receipt by the DFG of a grant application for research involving imported human ES cells led the Foundation to publish revised regulations in May 2001. These commended a step-by-step process for human stem cell research, starting with pluripotent stem cells that could be imported from abroad. If these cells were found to be insufficient for achieving the intended research goals, then the possibility of isolating ES cells from human blastocysts should be considered. (Note 4)
  • The German Parliament asked DFG to delay its decision on the grant application until a public consultation had been carried out. The Parliament established an Ad Hoc Commission, comprising both parliamentarians and experts, and in November 2001, the Commission judged that the lowering of embryo protection standards could not be justified. While a majority of Commission members favoured a total ban on importing ES cells from abroad, some felt that a ban in principle on imported ES cells could be subject to exceptions under certain restrictive conditions. (Note 5)
  • The latter view was accepted by a second advisory body, consisting of scientists, established by the German Federal Government. It was also adopted in the Stem Cell Act, which was passed in April 2002 by parliamentarians representing different political parties. The Act is based on the moral standards underlying the Protection of Embryo Act, which was left unchanged. Concerns that the import of pluripotent ES cell lines by German scientists might promote the creation of such cell lines abroad resulted in a ban in Germany on the import of stem cells from lines created after December 2001. (Note 6)

Discussion

  • There is no legislation governing the use of imported products derived from ES cells. Moreover, 10,000 children are born each year using IVF techniques and no stigma is attached to children so born, even though these were developed through research on embryos.
  • It is possible in the current climate for German scientists to carry out stem cell research, using imported stem cells, but not those from newly-created cell lines. Views on this might change if a life-saving technique were to be developed from stem cell research.

The Status of Stem Cell Research in Scandinavia

Professor Jan Helge Solbakk

Centre for Medical Ethics, University of Oslo

  • Three different stories from Sweden, Denmark and Norway respectively, all originating from the 1978 birth of ‘test tube baby’ Louise Brown and the birth 19 years later of the first cloned animal, Dolly the sheep. There is the question of who might be responsible for any lack of transparency and trust: the scientists, the lawyers, the ethicists, or Mother Nature?

Sweden

  • In 1978, a system of medical research ethics committees (RECs) was set up, the majority of whose members were recruited from the medical community, as this was seen as a guarantee of professionalism. The fact that ethical regulation was being determined by those positively biased towards medical research might explain why, since early 1980’s, Swedish researchers have been able to work on fertilised human eggs and early embryos. There are currently more than 30 research groups in Sweden working in the area.
  • A law formally regulating embryo research was introduced in 1991, and further regulation was not deemed necessary until January 2000, when researchers applied for approval of research into characterisation of stem cells harvested from surplus IVF embryos (Notea). After consultation with the Swedish National Council of Medical Ethics, the local REC judged that such research probably did not violate the spirit of the 1991 law, but felt that further clarification of the law was required. In addition, the medical branch of the National Council of Science established a working party to consider the production of embryonic stem cells solely for research purposes.
  • The working party reported in 2001, highlighting the principles of informed consent and of REC approval of each individual project, and the need for public scrutiny (Note b). The group did not accept the production of embryos solely for research purposes, although there was no suggestion that legislation to prevent this should be introduced. The working party also did not accept the production of embryonic stem (ES) cells through cell nuclear replacement (CNR), judging that there was no need for the technique to be used, and that its use might add greatly to the risk of the instrumentalisation of human life and that it might pave the way towards reproductive cloning. Although the National Council of Medical Ethics agreed in large part with the working party’s findings (Note c), the National Council of Science advised the Government to add an article to the 1991 law allowing CNR, and this is in the process of being passed (Noted).

Denmark

  • Research on embryos relating to IVF/PGD has been regulated since 1987, and individual projects require approval by a scientific ethics committee (Notee). In December 2001, the Danish Council of Ethics (Notef) published a report on cloning, including CNR. Council Members were unanimous in their disapproval of reproductive cloning, though 11 out of 16 were in favour in principle of deriving ES cells from surplus embryos or by CNR as long as there were potential medical benefits.
  • Concern that the creation of embryos for non-reproductive purposes would lead to demise of values (‘værdiskred’) elicited the recommendation that only surplus IVF embryos be used for research purposes. A unanimous Council recommended that ES cells should not become the subject of patents, and emphasised the need for research of adult stem cells. (Noteg)
  • In January 2002, the Danish Health Minister ruled that the law did not allow the donation of fertilised eggs for non-reproductive purposes, such as stem cell production, but did not govern the import of fertilised eggs from abroad for such purposes. An ad-hoc committee on genetic technology set up by the Government is due to give its report this year. (Noteh)

Norway(Notei)

  • The current Norwegian Minister of Health has proposed a law, soon to be presented to Parliament, which would ban all research on fertilised eggs or early embryos for any purpose, including production of stem cells by CNR and importation of cells or cell lines from abroad. This would replace the current law which had been passed in 1987. The law would not cover ES cells derived from umbilical cord blood or aborted fetuses.
  • The report (Notej) in February 2000 of a Working Party on ES cells established by the Ministry of Social Affairs and Health reflected Members’ differing views on ethically acceptable sources of ES cells. Two of the six Members felt that the only acceptable sources of ES cells were from still-born babies, spontaneous abortions and umbilical cord blood, but the other four felt more time was needed to consider the issues, and went on to agree that the use of surplus IVF embryos and aborted foetuses for stem cell production might be ethically acceptable, but that fertilised eggs created just for stem cell research was not.
  • The report was widely circulated, and though most institutions, including the National Committee of Medical Research Ethics and the Norwegian Medical Association, agreed with the Working Party’s majority view, the Minister for Health adopted the pro-life view and reflected this in proposals presented to Parliament in 2000 (Notek). However, shortly before Parliament was due to debate the issue, the Government was forced to resign, and the new Government retracted the proposal and resubmitted one with an opposing view, close to the position in the UK.
  • Following elections in September 2001, a new minority Government was formed and the debate scheduled for May/June 2002. Despite broad support for the Working Party’s majority position, the current Heath Minister will place before Parliament proposals for an almost total ban. Most parliamentarians have not really decided on the issue and are likely to follow the lead of the Health Minister currently in office. Thus the Norwegian regulation on stem cell research will probably be stricter than in Germany, whereas, given a slightly different political outcome, it could have been similar to the UK position.

Discussion