Stem Cell Research and the Human Embryo

The response of the All-Party Parliamentary Pro-life Group

To the Chief Medical Officer's letter of 22/9/99

concerning

The Expert Group on Cloning and Stem Cell Research

Contents

1. Introduction
2. Use of human embryos under the HFE Act
3. Proposed new uses of human embryos
4. Legal considerations
5. Mitochondrial diseases
6. Stem cell research
7. Alternatives to embryonic stem cells
8. A mature regenerative technology
9. Is the use of human embryos necessary?
10. References

 

1. Introduction

1.1 The Chief Medical Officer has invited [1] the views of interested organizations on a number of questions relating to the use of human embryos in cloning research. These relate specifically to the recommendations made by the Human Fertilisation and Embryology Authority (HFEA) in its report [2] that the purposes for which research on human embryos is permitted should be extended.

1.2 We set out our views on the issue of human cloning in detail in our response [3] to the HFEA consultation document [4]. In that document we reiterated our view that a human embryo should be accorded the same respect as any other human being, and our consequent opposition to its treatment as an experimental subject. We will not repeat these points here, but refer the reader to that document.

2. Use of human embryos under the HFE Act

2.1 The  Human Fertilisation and Embryology Act [5] (HFE Act) states that licenses shall  not be granted for research on human embryos unless
"it appears to the Authority to be necessary or desirable for the purpose of

a) promoting advances in the treatment of infertility,
b) increasing knowledge about the causes of genetic disease,
c) increasing knowledge about the causes of miscarriages,
d) developing more effective techniques of contraception, or
e) developing methods for detecting the presence of gene or chromosome abnormalities in embryos before implantation,

 or for other such purpose as may be specified in regulations."

2.2 The Act further requires that such licences can only be granted if the HFEA is satisfied that any proposed use of embryos is "necessary for the purposes of the research".

3. Proposed new uses of human embryos

3.1 The Human Fertilisation and Embryology Authority has recommended in its report that two further purposes be added to those listed above, namely: and has indicated that it would grant licenses for the production of cloned human embryos by nuclear substitution into egg cells (the 'Dolly' technique) for such purposes. [2]

4. Legal considerations

4.1 The report recognizes that the HFE Act (section 3 (3)(d)) "expressly prohibits one type of cloning technique, namely the nuclear substitution of any cell whilst it forms part of an embryo", and notes that nuclear substitution into an egg "is not specifically covered". It has taken this as legal authority to grant licenses for cloning by nuclear substitution into a human egg for research purposes.

4.2 It should be clear that the intention of Parliament in this section was to prevent the production of a cloned human embryo by nuclear substitution, and its failure to cover cases of nuclear substitution into an egg is a drafting oversight.

4.3 It is also clear that Parliament did not seek to make any ethical distinction between 'reproductive' and 'therapeutic' cloning, since the ban in section 3 (3)(d) applies equally to licenses for treatment (which could lead to a live birth) and licenses for research.

4.4 We do not consider that a responsible public body would make use of a legal loophole to license activities which Parliament clearly intended to ban, or to introduce ethical distinctions that Parliament rejected. In our view any authorization of human cloning, for any purpose, would properly require the modification by Parliament of section 3 (3)(d) and should not be attempted through regulations.

5. Mitochondrial diseases

5.1 The rationale for using nuclear replacement techniques in relation to mitochondrial diseases is stated in the report [2]

a woman suffering from such a disease could have a healthy child if the nuclear material from one of her eggs was transferred before fertilisation into a donor egg from which the nuclear material had been removed.
5.2 This techniques does not involve the direct manipulation of an embryo, since the nuclear replacement takes place before fertilisation. However we note that
  1. given current medical practice, it may be assumed that the egg would be fertilized in vitro, and that substantial numbers of human embryos would be created and destroyed experimentally in developing the technique.
  2. this amounts to germ line gene intervention, since the child (if female) will pass her mitochondrial DNA on to her own offspring.
5.3 We do not accept germ line gene intervention for reasons covered more fully in our statement on cloning [3], and we note that this is also the position of the overwhelming majority of responsible  commentators. A report of the UNESCO International Bioethics Committee has said that "all major statements about germline intervention condemn its present use" [6]. We do not consider that creating a genetically engineered child for particular parents is justified by the fact that a naturally conceived child may have had a genetic disease. Germ line gene therapy has profound implications for the future of humanity, and its acceptance should not be pre-empted by introducing such techniques piecemeal.

5.4 For these reasons we do not support the extension of the HFE Act in this way.

6. Stem cell research

6.1 The proposal for using human embryos for developing treatments for diseased tissues or organs relates to the use of stem cells derived from the embryos.

6.2 Stem cells are cells  "that have the ability to divide without limit and to give rise to specialized cells" [7]. Stems cells are found in early embryos of all species, before differentiation has begun, but also occur in the tissues of adult organisms. For example blood stem cells reside in human bone marrow and give rise to red and white blood cells throughout adult life.

6.3 Stem cells from early embryos are totipotent or pluripotent, i.e. able to give rise to all or most of the bodies cell types. Stem cells in the adult are by contrast partially specialized, and able to give rise to a limited number of cell types. Human pluripotent stem cells have been cultured both from early embryos and from aborted fetuses.

6.4 It has been proposed that stem cell research could be of benefit primarily in two different ways. First, in basic research:

At the most fundamental level, pluripotent stem cells could help us to understand the complex events that occur during human development. A primary goal of this work would be the identification of the factors involved in the cellular decision-making process that results in cell specialization. We know that turning genes on and off is central to this process, but we do not know much about these "decision-making" genes or what turns them on or off. [7]
The knowledge gained could have application to any number of medical problems, including cancer and birth defects.

6.5 Second, it has been proposed that stem cells could  be used directly as the basis for certain kinds of treatment:

Pluripotent stem cells, stimulated to develop into specialized cells, offer the possibility of a renewable source of replacement cells and tissue to treat a myriad of diseases, conditions, and disabilities including Parkinson's and Alzheimer's diseases, spinal cord injury, stroke, burns, heart disease, diabetes, osteoarthritis and rheumatoid arthritis. [7]
6.6 It is suggested that, in order to ensure tissue compatibility with the patient, stem cells could be derived from an embryo cloned from one of the patients own cells. It must be stressed that this research is in its earliest stages.
No one knows how to make a stem cell differentiate to form a specific tissue, says Roger Pedersen of the University of California, San Francisco. "The language is one of growth factors and molecular signals. What we don't know are the magic words needed to create each tissue." [8]

7. Alternatives to embryonic stem cells

7.1 It must be understood that human embryos are not the only source of stem cells for this kind of research. Recent  work using  mice points to the possibility of using stem cells derived directly from adult tissue in regenerative therapy.
New research indicates that adult neural stem cells previously thought to be committed to becoming either neurones, astrocytes, or oligodendrocytes can de-differentiate and reinvent themselves as haemopoietic precursors. This finding raises the possibility that adult human stem cells may some day be coached to grow into organs, regenerate damaged tissue, or reconstitute the immune system. The problem of immune rejection may also be circumvented if an individual's own cells can be used. It also means that the need for fetal cells as a source of stem cells for medical research may soon be eclipsed by the more readily available and less controversial adult stem cells. [9]
7.2 Dr. Evan Y. Snyder of Children's Hospital and Harvard Medical School in Boston has conducted studies on mice which show that the neural stem cells will convert themselves into other kinds of brain cells when injected into the adult mouse brain.

8. A mature regenerative technology

8.1 So, despite the fact that some have suggested using stem cells derived from cloned embryos directly as part of a programme of treatment, it is becoming increasingly clear that a mature regenerative technology would be unlikely to use such a methodology.

8.2 When the growth factors and genetic switches governing cell differentiation are understood, there would seem to be no need to utilize totipotent or pluripotent stem cells in treatment. It is more likely that tissue regeneration could utilize stem cells taken from the patients own tissues, or even ordinary, fully differentiated tissue. By the application of appropriate genetic switches, it would in principle be possible to culture any kind of cell in vitro, or to convert it, in a number of steps, into a stem cell or into any other kind of cell. Direct regeneration of tissues in vivo might also be possible.

It is "unlocking the body's capacity to repair and regenerate" declares Doris Platika, president and CEO of Ontogeny in Cambridge, Mass. Researchers at Ontogeny are treating animals with proteins with names as fanciful as Sonic Hedgehog, Indian Hedgehog and Patched - which all play an important role in the development of bone, cartilage, skin and hair - to stimulate the growth of the corresponding tissues in an adult. The dream is to get organs to regenerate in place inside the body, not implant a new part grown on the outside. [10]
Hence it does not seem likely that nuclear substitution (or the formation of a human embryo by any other means), would form any part of a mature treatment programme.

8.3 We do not dispute that research involving stem cells will make a contribution to determining the growth factors and genetic switches needed to make such treatment possible. We do question whether the use of stem cells derived from human embryos will be either necessary or desirable.

9. Is the use of human embryos necessary?

9.1 The question to be addressed, in the context of the HFE Act, is whether the use of human embryos is necessary for the purposes of this research. We submit that it is not. The discovery of the Hox (Homeobox) genes [11] has shown that mechanisms governing the basic body plan of many animal groups are remarkably similar. This implies that the growth factors and genetic switches in the human are likely to be very similar to those in other mammalian species such as the mouse.

9.2 There are a number of practical and ethical restrictions involving cloning research in humans. These include

9.3 For these reasons it seems most unlikely that research involving human embryos would be the preferred approach for discovering the basic mechanisms of cell differentiation. A more plausible scenario is that these mechanisms will be understood through research on the mouse and other animal models, and that regenerative treatments will be first developed in these non-human species. The application of these techniques to human tissue will be effected by comparison of human and animal tissues grown in vitro.

9.4 We do not say that no experiment involving human cloning for the production of stem cells could ever contribute to this process. We do say that such experiments do not appear to be necessary, and that their absence would not prevent progress in this field.

9.5 As we have remarked elsewhere, we see no merit whatever in the approach adopted by the HFE Act. The implication that research on human embryos involves some degree of moral wrong, but that this may be traded against possible benefits, is not only incoherent but contrary to all accepted principles of medical ethics as applied to research on human subjects [12].

9.6 Nevertheless the Act does require that experiments involving human embryos should be necessary for the purposes of the research. If this means anything it is surely that, where an alternative programme of research is available, licenses for research on embryos should not be granted. We submit that there is no case for extending the Act as has been proposed.

9.7 We are disappointed that the HFEA has sought  to extend the Act in this way, because it tends to confirm our worst suspicions: that the Act and the Authority together provide no real ethical restriction on the procedures that may be carried out on a human embryo, because the restrictions that exist on paper will always be removed as soon as any significant body of scientific opinion requests that they be so removed.

10. References

1. CMO's Letter on the Expert Advisory Group on Therapeutic Cloning in Humans, 2 September 1999. http://www.doh.gov.uk/cegc/cmolet.htm
2. Cloning Issues in Reproduction, Science and Medicine, HGAC/HFEA, December 1998. http://www.dti.gov.uk/hgac/papers/paperd1.htm
3. Response to the HGAC/HFEA consultation paper Cloning Issues in Reproduction, Science and Medicine, The All-Party Parliamentary Pro-life Group, April 1998. http://www.dgwsoft.co.uk/homepages/cloning/cloning1.htm
4. Cloning Issues in Reproduction, Science and Medicine Consultation Document, HGAC/HFEA, January 1998. http://www.dti.gov.uk/hgac/papers/paperc1.htm
5. The Human Fertilisation and Embryology Act, SCH. 2   3.-(2).
6. Report on Human Gene Therapy, Mr Harold Edgar and Mr Thomas Tursz, UNESCO International Bioethics Committee, September 1994. http://www.unesco.org/ibc/uk/actes/s2/chap3.html
7. Pluripotent Stem Cells: A Primer, National Institutes of Health, January 28, 1999. http://www.nih.gov/news/stemcell/primer.htm
8. News: Hold the champagne, New Scientist 14 November 1998. http://www.newscientist.com/ns/981114/norgan.html
9. News: Adult stem cells may be redefinable, BMJ;318:282, 30 January 1999. http://www.bmj.com/cgi/content/full/318/7179/282/b
10. Your Bionic future, Scientific American Quartery, Vol 10, No. 3, Fall 1999, p36.
11.  See for example The Homeobox Page, Thomas R. Bürglin, University of Basel, Switzerland http://copan.bioz.unibas.ch/homeo.html
12. Appendix A of [3]