Select Committee on Science and Technology Written Evidence

Memorandum 29

Submission from Professor Sir Martin Evans


  There is a confusion of the use of terminology and I attempt to provide a clarification of the use of the terms chimaera (chimera) and hybrid (with cybrid) as currently used in the context of mammalian cell biology.

  Human embryos and human cells in culture—including human embryonic stem cells—need to be clearly distinguished.

  Experiments involving chimaerism of experimental animals (including embryos) with human cells will be an essential tool in advancing the possibilities of stem cell based tissue therapy. These studies will be mainly with stem and precursor cells which are not embryonic stem cells although they may or may not have been derived from them. "Reach-through" regulation from HFEA is undesirable and probably impractical.


  In the White Paper "Review of Human Fertilisation and Embryology act December 2006" paragraphs 2.79 to 2.83 consider embryos combining human and nonhuman material. I consider that there is a lack of clarity in definition, which adds to the amount of concern being expressed.

1.   Biological experiments which combine two distinct cells or their components fall into at least three categories

1.1  Chimaera

  Two or more distinct, intact cell lines are combined to contribute to a structure. An example would be a chimaeric mouse made by aggregating two early embryos. This mouse (sometimes called tetraparental) has in most if not all its tissues and organs cells from both sources. These cells interact and cooperate, but do not combine or exchange genetic material. (As an exception, in certain tissues—most noticeably, the skeletal muscle—because there is a natural process of cell fusion during development the cells in the tissue contain genetic material from both the original embryos.) Such chimaeric mice are also made by adding embryonic stem cells to an early mouse embryo and here, the resulting mouse has tissues containing cells originating from the embryonic stem cells. Thus a chimaera in this usage of the term does not imply chromosomal or genetic mixing. Although most experimental mammalian chimaeras have been made from embryos or cells of the same or closely allied species one series of experiments inadvertently used mouse ES cells to make mouse-rat chimaeras.(1) These, in contrast to mouse-mouse chimeras, had a very small contribution from the foreign component. Earlier experiments to make rat and mouse chimaeras using early embryo manipulation also failed to produce extensive chimaerism in viable offspring.(2)

1.2  Hybrid

  Two or more distinct cells are fused together—cell hybridisation. This is usually an in vitro procedure and has been used extensively between species to derive cell lines with partial chromosomal contributions from one of the partners in order to carry out somatic cell genetics. It has also been used between cells of diverse differentiated type in order to study the controls of differentiation. These hybrid cells, whether or not grown into a cell line contain an admixture of the genetic material from both original partners.

1.3  Cybrid

  Components (less the nucleus) of one cell are fused into another cell with its nucleus. Conversely, the nucleus may be added back to the cytoplasm (without the nucleus) of another cell. In vitro, the product of this technology has been termed a cybrid (cytoplasm hybrid) and experiments of this sort have been largely used to attempt to study controls of differentiation. This is also the technique used in SCNT of a somatic cell nucleus into an enucleated oocyte. Thus this technique is essentially making a cybrid. The cell, contributing the cytoplasm (ie the oocyte) provides no chromosomal genetic material.

2.   Necessity of regulation

  2.1  I would also like to submit that legislation and regulation should seek to permit and indeed promote scientific progress, but must prevent misuse. In this context, the only area for foreseeable serious misuse of experiments which combine human and animal material, particularly in an embryo, are those which involve allowing development in vivo.

  2.2  There are several problematic scenarios. The one which would involve development of an experimentally manipulated embryo in a human is, and should be, outlawed. The other is allowing development of an extensively humanised embryo in vivo in another species. This needs to be tightly regulated. Regulated, but not outlawed because there are potentially very important studies, which will be needed if and when embryo produced cells approach therapeutic use.

3.   Distinction between ES cells and embryos

  3.1  In this context, I believe that it is very important to differentiate between human embryos and human embryonic stem cells, and between their use entirely in vitro and in embryo manipulation. Tissue culture cells—no matter their developmental potential—are not embryos. I consider that the attempt to regulate the use of entirely properly derived cells and cell lines by a "reach-through" from the HFEA regulations is misguided. Regulation is entirely appropriate at the stage of use of human embryos. Regulation will also be entirely necessary at the stage of human therapeutic application of the products of stem cells. Between the two the UK could benefit by using the lightest possible touch. It is also pertinent to observe that cell cultures intended for therapeutic applications in tissue therapy will not be ES cells but populations of precursor cell: their differentiated derivatives. These cells may or may not have arisen from human embryos at their effectiveness will need to be tested in animal models—ie in chimaeras.

January 2007

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