Experiments on Embryos

Anthony Dyson, John Harris

• Publisher: Routledge
• Year: 2012
• Print ISBN: 9781138445628
• eBook ISBN: 9781134985982
• Topic: Philosophy
• Subtopic: Philosophy History & Theory

Covering scientific, legal, ethical, historical, theological and public policy aspects of human embryo research, the cases for and against are put strongly and clearly. Scientific evidence is cogently presented by leading embryologists.

Chapter one
Contemporary and future possibilities for human embryonic manipulation

Mark W. J. Ferguson

Introduction

This chapter describes current possibilities for the manipulation of human embryos and speculates on likely future developments in this area. It focuses on what is, or could be, feasible in scientific terms and attempts to analyse, from an objective standpoint, what could or could not be done. It makes no attempt to consider the ethics of such manipulations, nor to address whether such manipulations should be performed. It also addresses some earlier speculations about future possibilities in the field of human embryonic manipulation from the standpoint of analysing whether they are scientifically possible or impossible.

This chapter does not consider possible advances in techniques, for example improvements in methods of recovering eggs, of fertilizing them in vitro and replacing them in the mother, or improvements in the screening of sperm or in the in vitro culture conditions. I have no doubt that major advances will be made in these areas and that they will have a significant clinical impact, particularly for the treatment of infertile couples. However, from the perspective of this book, they pose few new ethical problems. Instead they are merely better ways of doing the same thing, with a greater chance of success. For this reason, detailed consideration of such advances is outside the scope of a chapter whose aim is to lay the scientific framework for future ethical debate.

It must also be emphasized that many of the manipulations of human embryonic development which I will describe do not necessarily require in vitro fertilization. It would, for example, be theoretically possible to recover early fertilized human eggs, to conduct such manipulations, and then to reimplant them into the mother. However, the logistics of such operations are quite mind-blowing and it therefore seems likely that such manipulations will be conducted on embryos derived from in vitro fertilization protocols. The point is worth making however, because there is a distinction between discussing the ethics of in vitro fertilization per se, and the ethics of human embryonic manipulation which does not of necessity depend upon in vitro fertilization, but which is technically facilitated by it, and is likely to be the only logistical way of conducting such manipulations on a wide scale.

I am also acutely aware of the problems surrounding future speculations. On the one hand there is the argument that if you can predict it, the advance will probably not be very important, as most major advances break new ground in areas which people had not previously considered. On the other hand, some of the possibilities which I predict may turn out to be unachievable and I feel certain that I have failed to predict at least some major future therapies. Nonetheless, I believe that there is value in trying rationally to assess what may be scientifically achievable so that at least the ethics of such procedures might be considered.

Prenatal diagnosis

Advances in the prenatal diagnosis of many genetic disorders have accelerated markedly in the past few years. In early days chromosomal analysis and certain biochemical tests were the mainstay of the prenatal diagnosis. All that has now changed with the advent of numerous genetic probes to detect the presence or absence of a large number of normal or mutated genes within the genome. These genetic probes have opened up a whole new horizon for the early detection of human disease and disease susceptibilities. First, the probes are very specific and can be used to detect precisely small defined aberrations in genotype. It seems highly likely that large panels of these gene probes will be available within the next few years; already many are available. Second, accompanying the explosion in human genetic probes has been a corresponding development of the technology for obtaining large enough quantities of host DNA to conduct such analyses. It is now possible to take a single cell, extract the DNA from it and then, if one knows the region of the genome one wishes to examine, to amplify up that region to obtain enough DNA for analysis by gene probing. Currently there are some diseases which are diagnosable using the quantity of DNA present in a single cell. This technology is rapidly expanding and it seems likely that nearly all future diagnoses could be made on the basis of a single cell biopsy.

Such technology now means that single cell biopsy of early human embryos growing by in vitro fertilization techniques is a possibility. This DNA could be amplified and screened using a panel of DNA probes in order to detect the presence or absence of a variety of normal or mutated genes. This opens up two further possibilities. First, a panel of embryos generated by in vitro fertilization could be screened and the ‘best’ one returned to the mother for reimplantation and further development. Second, specific gene therapy to correct various genetic defects is achievable (see later) as embryos carrying such genetic defects can now be detected.

At first sight this seems a relatively straightforward issue largely because gene probes are currently available for some of the major genetic diseases. In the future, therefore, it may be possible to detect at an early stage such disorders as Huntington's chorea, cystic fibrosis, cleft lip and palate, spina bifida, etc. However, much progress is now being made on elucidating the genetic basis of a large number of other diseases, including susceptibilities to disorders which involve a genetic and environmental component, e.g. cancer. Moreover, the development of a genetic and physical map followed by complete sequencing of the estimated 3,500 million base pairs making up the human genome are now technically feasible: all that is required is the will and the money (about 50 pence per base pair). The time estimated to complete this massive task varies from 3 to 30 years, depending upon the international resources devoted to the project; the ever-increasing sophistication of DNA sequencing machines is likely to reduce the time and the cost in financial and man-hour terms.

In parallel with this task will be an explosion in the mapping of particular genes to various regions of the genome, a greater understanding of chromosomal organization and gene control, and a solid database of genetic susceptibilities to various disease states and how these may interact with the environment. Having mapped the genome once, it is likely that techniques will evolve for the rapid sequencing of important areas of individual human genomes. This being so, there is every reason to believe that inside 50 to 100 years every human being could have his genome (or at least important regions of it) mapped either at birth or as a very early embryo. Individual genetic defects and susceptibilities to various diseases would then be known. Preventative health care strategies could be evolved for individuals on the basis of their known genetic susceptibilities.

This opens up very wide-ranging possibilities for the screening of embryos to be reimplanted as part of an in vitro fertilization programme. Embryos could not only be screened for the major genetic diseases but also for a variety of other parameters including such things as susceptibility to adult cancers, infections, etc. Different embryos will show widely differing profiles of susceptibility or resistance to various disorders when such widespread screening is applied. Therefore decisions about which embryos to reimplant will be all the more complex. Indeed, it seems likely that the number of embryos fertilized in vitro would be the rate-limiting step in any kind of purposeful selection experiment. The variation between embryos is likely to be so great that one would have to screen thousands, if not millions, of embryos from individual couples if one were to attempt deliberately to select certain consistent genotypes on a population basis. I therefore have no fears about the potential to manipulate the human gene pool (for good or bad); the sheer numbers required to achieve this precludes it as a rational possibility. I also believe that natural selection has left much to be desired, in terms of the human gene pool, and individual selections at this level are unlikely to have any detrimental effects, only advantageous ones. Therefore, scare-mongering based on manipulation of the human gene pool by sophisticated screening is unjustified.

What is, however, justified is a consideration of how decisions will be made concerning which embryos to reimplant, given the likely range and sophistication of available prenatal tests. With the limited numbers of embryos generated by in vitro fertilization it seems probable that each of these embryos (like those generated by conventional reproductive strategies) will have problems in some area or another. The decision will therefore be one of trade-offs. Who will help the couple to decide which embryos to reimplant, given a perplexing number of trade-offs in relation to likely susceptibilities to adult diseases? What criteria should we use to make these decisions?

These genetic probes could be used not only to screen for disease susceptibilities, but also for likely adult phenotypes such as sex, height, etc. Much scaremongering has abounded about the possibility of manipulating the sex ratio of the human species. However, it should be remembered that this possibility already exists: a mother may have an amniocentesis during her pregnancy, determine the sex of the fetus, and elect to have an abortion if it is not of the desired sex; societies may practise sexually selective infanticide. In fact, selection of the sex of the embryo is much more likely to be achieved by selection of sperm. Techniques are already being developed which allow the separation of future male- and female-determining sperm from a variety of domestic animals. It seems likely that such techniques will improve in the next few years and may be applied to the human situation. Logically the easiest way to manipulate the sex of the embryo is not by genetic screening of embryos developing by in vitro fertilization, but rather by selection of the sperm, and artificial insemination in vivo or selective fertilization in vitro. In the latter, all the embryos fertilized in vitro (or at least a high percentage of them) would be of the desired sex and these could then be screened using gene probes for major disorders, etc; this is the most logical approach given that the number of embryos generated will be the rate-limiting step in screening for the best one to reimplant (see earlier).

Such developments highlight another likely possibility, namely better criteria for the selection of ova and sperm for the in vitro fertilization procedure. It may be possible to extend such selection beyond such parameters as likely fertilizing capacity, potential to grow in vitro, potential to reimplant, etc., to cover characteristics which may be displayed in the embryo. This is an area which has currently not been explored using genetic probes but if techniques were available for the removal of small pieces of DNA from ova or sperm and their replacement after screening, then it might be possible genetically to screen the gametes and make rational predictions about the likely outcome after fertilization. I believe this is a theoretical scientific possibility, but is probably a long way off. At the present time it seems likely that the sheer logistics and technical effort required would indicate that ova and sperm would be screened only using crude parameters leaving the more sophisticated investigations of genetic constitution to a later stage when they would be dealt with by single cell biopsy of the embryo followed by screening using a number of gene probes.

It has also been suggested that in vitro fertilization programmes may be used to create banks of good embryos generated when the mother is in peak reproductive performance which could then be reimplanted, should the mother so desire, later in life when the natural risk of such disorders as Down's syndrome are much higher. Certainly there is some sense in this proposal, particularly in relationship to age-related chromosomal or genetic aberrations of the embryo such as Down's syndrome. However, it is well known that the maternal environment, e.g. the amount of blood flow to the uterus, the nutrition of the embryo, the volume of amniotic fluid, etc., all play a major role in successful fetal outcome. It is unclear how well the ageing human female reproductive system would cope with such good embryos. For certain, they would not have the major malformations like Down's syndrome, but perhaps they would be less than optimal in their development. I would therefore only see such techniques being applied when there was some pressing need for the mother to be pregnant in later years. Its use is therefore likely to be limited. One would certainly not advocate such procedures for the routine delaying of pregnancy, e.g. until the mother had achieved a suitable prominence in her career. Such widespread voluntary practices would be contraindicated (a) because of the likely poor environment for the embryo in the ageing female reproductive system, and (b) because of the simple fact that the older you are when you produce children, the less time you are likely to have (in terms of life expectancy and quality of life) to bring them up to an age at which they become independent.

Somatic line manipulations

A somatic line manipulation would involve alteration (e.g. of the genes) of the cells of an individual embryo so as to, for example, correct a genetic defect. This manipulation would be limited to the cells ofthat individual embryo and would not be passed on to its offspring. This is in contradistinction to a germ line manipulation (see later) which would alter the genome not only of that individual embryo but also of its offspring.

It follows that if one can detect genetic disorders in early embryos then some of these could be corrected. Thus, for example, if a particular gene was deleted in an individual embryo this gene could be reinserted into the correct stem cell line thus correcting the genetic defect and preventing a major adult handicap. Techniques exist for the introduction of specific pieces of DNA into cells (see later): such manipulations are therefore currently possible and most likely to be utilized for straightforward single gene defects.

Moreover, somatic line manipulations may not necessarily involve interference with the early embryonic genome. Instead the manipulation may be at the cellular level. Thus, for example, early embryos which had abnormal cells could have these removed, either surgically or by killing them using toxins coupled to specific monoclonal antibodies which specifically recognized those abnormal cells. More likely would be the introduction of additional cellular material to make an embryonic chimera. For example, if the embryo were deficient in cells making a particular type of hormone or particular blood cells, then stem cells for such components could be introduced into the embryo to correct the defect.

This raises two questions. First, the source of the donated cells: this matter is dealt with in a later section on embryonic /fetal transplantations. Second, the likely stage of development at which such manipulations would take place. It seems likely that most somatic line cellular manipulations would occur in later embryos or fetuses and as such the manipulations are likely to be carried out on embryos regardless of whether or not they have been fertilized in vitro or by conventional in vivo mechanisms. Such procedures have already been performed on human embryos (see later section on embryonic/fetal transplantations).

Germ line manipulations

Unlike somatic line manipulations germ line manipulations are likely to be almost exclusively at the DNA level. In recent years the technology for such genetic manipulations has advanced dramatically in experimental animals and I first provide a summary of such technology and how it is being used in animals, before describing how it could be used in the human situation.

It must be made clear that construction of transgenic animals is currently a fairly difficult laboratory procedure and that the difficulties increase as one ascends the vertebrate kingdom. It seems likely, therefore, that there will be some pro...

Table of contents

• Cover
• Half Title
• Full Title
• Copyright
• Contents
• Preface
• Acknowledgements
• Notes on contributors
• Introduction
• 1 Contemporary and future possibilities for human embryonic manipulation
• 2 Historical perspectives on human embryo research
• 3 Ethics and embryology: the case for experimentation
• 4 The case against experimentation
• 5 Embryos and hedgehogs: on the moral status of the embryo
• 6 At Heaven‘s command?: the Churches, theology, and experiments on embryos
• 7 An irresolvable dispute?
• 8 Experimentation: some legal aspects
• 9 The challenge for Parliament: a critique of the White Paper on Human Fertilisation and Embryology
• Bibliography
• Index