Genetic engineering: animal welfare and ethics.

A discussion paper from the Boyd Group.

September 1999


Preface

The Boyd Group is a forum for the open exchange of views on issues of concern related to the use of animals in science. Members are from a diversity of backgrounds and span a wide range of professional and public opinion. They include veterinarians, scientists using animals, members of animals welfare organisations, anti-vivisectionists, members of bodies funding or directly engaged in research, philosophers and others. The Group's objectives are to promote dialogue and, where there is consensus, to recommend practical steps towards achieving common goals.

This paper summarises the Boyd Group's discussion of issues raised by the genetic modification of vertebrate animals, including:

  1. fundamental ethical objections to the production and use of genetically modified animals;

  2. consequences for animal welfare, and strategies for improving understanding of welfare effects;

  3. benefits sought from genetic modification, and the need to use transgenic animals.

The paper aims to disentangle the broad arguments in these areas, by illustrating both the diversity of perspectives and, in particular, the common ground within the Boyd Group. Where consensus emerged in discussion, practical recommendations agreed by the Group are reported. It is hoped that the report will be accessible to a wide audience. To this end, brief, non-technical descriptions of the factual background to the issues are included.



1 INTRODUCTION

1.1 What does genetic modification of animals involve?

Genetic modification, or genetic 'engineering'a of animals involves the addition or deletion of part of the genetic code (DNA) of an animal in order to change the animal's characteristics (its phenotype). Change in phenotype can be brought about either through expression of introduced DNA, or through addition, deletion or substitution of some part of the animal's own genetic material. The aim is usually that the genetic alteration should also be present in the germ line cells, so that the changes can be passed on from generation to generation.

A range of methods is available for altering the genetic material. Techniques include pro-nuclear micro-injection (available since 1980, and used in a range of species); embryonic stem cell manipulation (in mice, and very recently, primates); and (also recently) the ability to modify farm animals by nuclear transfer (1,2).

This paper is concerned with non-human vertebrate animals, which are genetically modified and used

Latest Home Office statistics record that in Britain in 1997, 352 752 scientific procedures performed under the auspices of the Animals (Scientific Procedures) Act 1986 involved the use of genetically modified animals, amounting to 13% of all recorded scientific procedures (3). The majority (98%) of the animals involved were mice, and the remainder mainly rats, pigs and sheep (see Table). Forty percent of the animals were used for fundamental and applied biomedical research and testing, whilst the remainder were 'breeding stock', used to maintain the genetically modified lines. The latter animals were bred from genetically modified parents but were not used in research or testing procedures - the regulations apply to such animals because their welfare may be affected by the genetic modification itself.

Scientific procedures peformed on genetically modified animals in 1997
Source: Home Office(3)

Type of genetically
modified animal
No. procedures
for research & testing
No. procedures
for breeding
Total number
procedures
Mouse 137426 207556 344982
Rat 2115 2343 4458
Pig 266 1219 1485
Sheep 1472 0 1472
Fish 200 0 200
Domestic fowl 119 0 119
Rabbit 28 8 36
TOTAL PROCEDURES: 141626 211126 352752

1.2 Why genetically modify animals?

A range of benefits is sought from genetic modification of animals. Most work is basic or applied medical or biological research, aimed at understanding gene function and regulation, or studying human or animal disease. The ability to replace or alter individual genes, or delete them, can assist in investigating the natural functions of a gene in health and disease, the factors within the body that control it or interact with it, and the interplay between genes and external factors, such as diet or environment. Much experimental genetic modification is done on cells, plants or simple organisms, such as the nematode worm, C. elegans - and such alternatives are used in preference to vertebrate (or complex invertebrate) animals wherever possible.

The following are some examples of the benefits that can come from using genetically modified mice and other vertebrate animals:

(i) Use of laboratory animals - mainly mice The ability to insert or delete genes in the genomes of mice has assisted in unravelling complex developmental processes in which genes are switched on and off, and tissues become differentiated.

Many different mouse models mimicking human disease, and/or possessing relevant human receptor sites, are used in studying the mechanisms by which disorders (such as immunological, neurological, inflammatory, metabolic and developmental abnormalities and cancers) are caused, and in working towards developing more effective treatments, such as pharmaceutical or gene therapy (4).

(ii) Use of farm animals
In Britain, a minority of scientific procedures involves genetically modified farm animals. In 1997, around 1 860 such animals (sheep, pigs and domestic fowl) were used in scientific research procedures, the majority for 'applied' purposes. A range of potential and actual benefits can come from such work, including:

Farm animals have also been genetically modified in attempts to increase aspects of their 'productivity', such as growth rate or wool production, though no such work is currently carried out in Britain. There are major difficulties in using genetic engineering to modify such complex traits, which are controlled by a number of genes, and conventional selective breeding currently proves more economically viable as a means of modifying such characteristics (6).

1.3 What are the ethical concerns?

Alongside the potential benefits, genetic modification of animals raises a variety of ethical concerns. In thinking about these concerns it may be helpful to distinguish between:

  1. fundamental moral objections either
    1. to the human use of animals generally, or
    2. specifically to their genetic modification; and
  2. concerns about the consequences of genetic modification (about the various harms which might be caused, and about the goals and potential benefits of the work).

(a) Fundamental moral objections
(i) Objections to the use of animals in general

Most people, nowadays, would agree that animals can have 'interests' (interests not to be caused pain and suffering, for example), but there is considerable debate about whether,

and to what extent, these interests may be forfeited for human interests. Many arguments (about consciousness, self-consciousness, cognitive ability, language capacity, moral sense, quality of life, and evolutionary status, for example) have been used in attempts to find morally relevant differences (or, conversely, similarities) between humans and animals which could justify (or preclude) treating animals as means to human ends. None of these arguments so far has succeeded in attracting general philosophical agreement.

There is a spectrum of opinion regarding the relative weightings that should be accorded to human and animal interests. At the ends of the spectrum are the absolutist positions - that human interests are always sufficiently important to outweigh animal interests, or that they are never sufficiently important. The latter view, at its simplest and strongest, is that if it is wrong to conduct certain experiments on humans, it is also wrong to conduct them on animals. This moral position is not negotiable, although the animal interests focused on may differ. For example, some animal welfarists object to any experiment which causes animals pain and suffering, whereas some advocates of animal rights object to all human uses of animals, whether or not pain and suffering is involved.

(ii) Objections to the genetic modification of animals in particular

A different kind of moral objection is specifically concerned about the nature of genetic modification. The concern may be expressed, for example, by objecting that genetic engineering is 'unnatural', that it amounts to 'playing God', and that it 'debases animals' by treating them as 'commodities'. A related view is that there are special moral objections to the creation of animal strains which suffer throughout their lives because of their genetic make-up.

(b) Concerns about the consequences of genetic modification of animals

The argument that it is acceptable to use animals as means to at least some human ends usually appeals to the benefits of that use - that, in at least some cases, the benefits of using animals can outweigh the harms that are caused. Here, therefore, the main ethical concerns are about the consequences. In the case of genetic modification, there may be concern about consequences for the welfare of modified animals, and about the harms caused during their production. There may also be concern about the hazards which modified organisms might pose to human and animal health and to the environment. Or, again, there may be concern about the balance of harms and benefits arising from genetic modification.

The remainder of this paper concentrates on a (ii) and (b) above - fundamental objections and consequential concerns specific to genetic modification.

 

2 FUNDAMENTAL MORAL OBJECTIONS TO GENETIC MODIFICATION

Fundamental moral objections to genetic modification may be expressed in the argument that genetic engineering 'fails to respect the genetic integrity' of animals, because it involves 'mixing' of genetic material between different species and even between different Kingdoms (between animals and plants for example)b. Anxiety, distaste, or even revulsion, may be expressed about the 'unnatural' mixing of kinds - about creating chimeras, about altering the 'telos' of species (so as to interfere with a pig's 'pig-ness', for example), about crossing the species barrier, and about the mixing of genes between humans and other animals. These moral objections may arise, for example, from widely held philosophical or religious world-views, or from deep-seated emotions or aesthetic values. (Associated with these fundamental objections may be consequentialist fears that limited experiments in such areas can lead down 'slippery slopes', perhaps culminating ultimately in ethically indefensible human eugenic practices, or creating bizarre animals and/or treating animals as mere commodities.)

In response to these objections it can be argued that talk of 'mixing' genomes does not reflect the nature of genetic engineering as currently practised. Although there is a random element, present practice usually involves the relatively precise transfer of only one or two genes - a small fraction of the genome of most recipient organisms (which may contain upwards of 100 000 genes). Each gene codes for a specific protein, and it is only the combined effects of expression of a multitude of genes within the living organism that confer, say, its 'pig-ness' or its 'human-ness'. Furthermore, many genes are conserved (are similar) between different species.

However, transfer of, for example, even a single human gene into a pig can result in expression within that pig of something typically human - a human protein, such as human growth hormone. The human protein may be only very slightly different from the pig protein but nevertheless it is found naturally only in humans. Furthermore, whilst currently it is feasible to transfer only a few genes between species, in future it may be possible to transfer many more genes - and we therefore need to be alert to the biological implications and related ethical concerns that might arise.

A further response to fundamental objections to genetic modification is the argument that talk of 'transgressing the species barrier' is inappropriate, because species boundaries are not necessarily hard and fast - species change naturally through evolution, for example. Similarly, the characteristics of many animal and plant species, traditionally, have been altered artificially through selective breeding, so it can be argued that direct genetic modification is merely an extension of these traditional breeding techniques, and thus poses no new fundamental ethical concerns. Thus, if genetic modification of animals falls prey to charges of 'playing God', 'unnaturalness' and 'treating animals as commodities', these same charges should be levelled at selective breeding.

However, although species change through natural events, it is extremely difficult to challenge species boundaries in selective breeding. Direct genetic modification is different from both these processes in that, potentially, it offers limitless possibilities for transferring specific genes between widely different species (although not every combination will be viable). Genes can also be transferred from a variety of different species into the same animal, and such genetic change(s) can be achieved within a single generation. (Further points of comparison with selective breeding are explored below.)

Members of the Boyd Group differ in their evaluations of these arguments. This is not surprising. Value judgements are inevitable in ethical discussions: different people respond to the same situations in a variety of ways, and arrive at different conclusions. With regard to genetic engineering of animals, moreover, perception of the fundamental issues can be complicated by concerns about what will be possible in the future, and whether scientists can be trusted not to stray into ethically controversial or objectionable territory. The latter concern, in particular, is fuelled by worries about the pressures brought to bear by increasing commercialisation of such research, or from questions about the ethics of research raised in the media.

Fundamental moral objections to the genetic engineering of animals, and concerns about what might be possible in future, are sufficient to persuade some members of the Boyd Group that such work should be severely limited, or abandoned altogether. The consequences for animal welfare, moreover, may be judged so detrimental that it is argued that the benefits of using such animals can never (or only in the most exceptional cases) outweigh the harms.

For other members of the Boyd Group, fundamental objections do not, in themselves, provide sufficient reason for avoiding research involving the genetic manipulation of animals in order to achieve the kinds of benefits described above. They agree, however, that such concerns give pause, and should be addressed, since perceptions of what is morally acceptable are contestable and can change. At a time of rapid scientific change, it is particularly important to listen to all reasoned arguments that highlight areas of ethical concern.

 

3 CONSEQUENCES OF GENETIC MODIFICATION

Whatever their position on fundamental moral objections to genetic modification, members of the Boyd Group are agreed that whenever animals are genetically modified and used in science, there should be careful, detailed and critical scrutiny of the consequences of that use. This should include consideration of the special potential of genetic modification to cause welfare problems in animals.

3.1 Consequences for animal welfare

Here, two aspects need to be considered: the harms that can be caused during the production of genetically modified animals, and the welfare of the resulting modified animals. In the UK, all scientific procedures likely to cause pain and distress to animals are regulated under the Animals (Scientific Procedures) Act 1986 and must be licensed by the Home Office. The harms caused to the animals must be minimised, and the procedures can only be carried out if the likely benefits are judged acceptable in relation to the harms.

3.1.1 Production of genetically modified animals

The techniques used in genetic manipulation of animals include administration of drugs to donor female animals, in order to induce superovulation, followed by timed matings and collection of fertilised eggs (by killing the donor animals if mice are used, or by laparotomy in larger animals). After they have been genetically manipulated in vitro, the modified embryos are then implanted into surrogate mothers, by laparotomy.

Both induction of superovulation and laparotomy are established techniques which, increasingly, are employed in selective breeding of farm and laboratory animals. Laparotomy is carried out under general anaesthetic. Nevertheless, laparotomy can cause post-operative pain, and superovulation can cause discomfort. In both cases, appropriate analgesia should be administered. Preparation of surrogate mothers involves mating them with sterile males to produce a 'pseudopregnancy', and the males must therefore undergo vasectomy under general anaesthetic. Sometimes, the donor female animals are mated when very young, and this can be stressful (7).

Aside from the direct effects of the techniques involved, fetal death can occur during development in utero, and some additional deaths can occur post-natally. One study (8) found that, in experiments involving pro-nuclear micro-injection of seven different gene constructs into mouse embryos, 1360 out of a total of 1585 embryos survived micro-injection (and in some cases overnight culture) and were implanted into pseudopregnant females. 29% of the implanted embryos survived to weaning (with a range of 21% to 42% between the seven experiments). Just under a quarter of these pups proved to be successfully genetically manipulated (that is, 7% of the implanted embryos, range 3% to 11% across the experiments).

Such proportions are likely to vary considerably from case to case. It is uncertain at what stage in development fetuses can experience pain and distress, or how far the welfare of the mother is compromised by fetal death. However, in the larger farm animals it is known that miscarriages cause distress to the mother. Losses during production mean that relatively large numbers of donor and recipient animals must usually be used in order to produce a relatively low yield of genetically modified animals.

In general, there is a lack of published data on mortality rates and ages at which death occurs during production of genetically modified animals, and there is a need for more detailed analysis of the full range of welfare problems caused during such production.

3.1.2 Welfare of resulting animals

In some cases, genetic modification appears to have no impact on the welfare of resulting animals; in theory, it might in some cases benefit animal welfare; and in other cases there are certainly adverse welfare effects, which encompass a range of severities (9,10).

Welfare can be compromised in two main ways.

(a) For research purposes, gene deletions ('knock-outs'), mutations, or defective genes may be introduced in order deliberately to cause or simulate a wide range of genetic diseases or developmental or gene function abnormalities.

(b) In any case of genetic manipulation, unintended deleterious or harmful side effects can occur. Such side effects may be caused when the new genetic material is expressed, and unpredicted physiological changes occur; or they may be caused when the introduced DNA disrupts the function of one or more of the animal's own genes. The latter is a result of randomness of integration of the new genetic material into the recipient animal's genome, in particular when the pro-nuclear micro-injection technique is used. Many such disruptions prove fatal to the developing embryo. When the effect is not lethal, the welfare of the resulting animal can be seriously compromised (mice have been born with deformed limbs or kidney malfunction, for example - see reviews in 2,9). In mice, the embryonic stem cell manipulation technique now offers the possibility of better gene targeting.

Whilst most genetic modifications tend not to benefit the animals concerned, genetic modification might also aim to benefit animal welfare, for example by producing better disease resistance. To take a hypothetical example, if all pigs (everywhere) were resistant to foot and mouth disease, there would be enormous benefits for pig welfare. In other cases, genetic modification might be welfare 'neutral'. This might be the case if there is 'no change from the average for unmodified animals' (as for example in most, but not all, animals modified to produce medically important proteins in their milk - 11); or welfare is no different from that of animals produced by selective breeding (1). This last point again raises the question of whether there are significant differences in the effects of direct genetic modification and of conventional selective breeding.

3.1.3 Comparison with selective breeding

Both direct genetic modification and selective breeding have the potential to improve animal welfare and to produce welfare problems. Direct genetic modification can produce particular changes in the genetic material more rapidly than selective breeding - yet, along the way to the desired goal (the desired phenotype), the outcomes of genetic manipulations can be less predictable than the outcomes of selective breeding. Selective breeding tends to build on previous results in step-wise fashion, whereas direct modification of the genome can produce more novel, surprising and wide-ranging phenotypic effects, with greater potential to compromise welfare, in one step. This is particularly the case in knock-out experiments, when it can be difficult to predict the effects of genetic deletions; and, more generally, when pro-nuclear micro-injection is used, because, as already noted, the introduced DNA is randomly integrated into the recipient animal's genome.

It can also be argued, however, that because the welfare changes brought about in selective breeding may be more gradual, they can also be more insidious, and difficult to spot at an early stage. The gradual nature of these changes can also lead society to accept features - in some breeds of pet, for instance - which would generally be considered unacceptable if introduced by genetic modification.

3.1.4 Improving understanding of welfare effects

Consideration of the consequences of producing and using genetically modified animals is complicated by the difficulties involved in predicting both the welfare 'costs' to animals, and the benefits likely to be afforded by the modified phenotypes. As in other research areas, it is possible that potential costs and benefits can be assessed from scientific understanding and previous experience (including the results of similar experiments), but in this area much new ground is being covered rapidly and the potential effects of the procedures are often uncertain. It is therefore especially important that the justification for such work is reassessed as the work progresses: that is, as it becomes more possible to predict likely costs and benefits from experience of previous related work. On the welfare side, it is important that the effects of genetic manipulations are documented in as much detail as possible - and, equally, on the question of benefits, to record whether the desired benefits actually are achieved.

Databases on the characteristics of genetically modified animals tend not to indicate welfare problems. Some effects - the more 'cryptic' abnormal effects, such as changes in behaviour - may be difficult to spot, and 'tolerance' of adverse effects can depend on the scale of animal use, and the size of animals involved. For example, some people may have relatively little interest in the apparently minor side-effects of genetic manipulations of a few mice used in laboratory research, whereas in larger-scale production of farm animals there will usually be an attempt to assess all possible effects.

There is a need for greater awareness of the welfare problems posed by abnormal effects, improvement in surveillance and data gathering on such effects, and improvement in data sharing. In particular, there is a need for:

3.2 Concerns about the numbers of animals used

There has been a rapid rise in the production and use of genetically modified animals. Comparative data are available from 1995 to 1997, and show that number of scientific procedures performed on genetically modified animals has risen by 64% over the period (3)c. There is currently a phase of relatively large-scale 'grasping of the opportunity' to do new studies using the new technology. Many more projects are employing genetically modified animals - though it might be the case that, within each individual project, the validity of the animal models is enhanced, so that 'results may be obtained more quickly and, ultimately, after the use of fewer animals' (1).

Arguably, the increase in use of genetically modified animals can be regarded as a 'necessity' of the moment, in that the justification is based on circumstances that did not exist 15 years ago and which might change over time, as benefits are realised and the need to use animals diminishes. On the other hand, with upwards of 100 000 genes in the mammalian genome and rapid progress in sequencing the human genome, the potential for new studies is vast, and the number of animals used could well continue to increase in the foreseeable future.

It would be helpful if the Home Office statistics included more information on the scale and nature of the different uses of genetically modified animals, and the extent to which welfare is compromised, in terms both of losses in production and of effects on the resulting animals. It is understood that the Animal Procedures Committee is considering whether more such information might be included in the statistics (12). (See also the recommendation of Langley and D'Silva [13] with respect to pigs produced in xenotransplantation research.)

3.3 Concerns about safety

A utilitarian justification for producing and using genetically modified animals must take into account potential risks to humans and other animals, as well as to the wider environment. While this is a major concern of regulatory bodies, these vary in scope and efficacy between countries, and much more research on safety aspects is needed to inform their decisions.

Here, we simply note that several related categories of concern about risks to safety need to be considered:

3.4 Goals and potential benefits of genetic modification of animals

The main uses of genetically modified animals include: uses in biomedical research and testing generally; production of medically important proteins; development of xenotransplantation; and as farm animals with increased 'productivity' or disease resistance.

3.4.1 Biomedical research

By far the most common use of genetically modified animals is in biomedical research (fundamental and applied research into human and animal development, gene regulation, brain receptor chemistry, genetic disorders and development of human gene therapy, for example) and the related development and testing of new pharmaceutical products. These uses tend to involve small laboratory mammals - in the vast majority, mice.

Case-by-case judgements of the necessity to use genetically modified animals are difficult. There is a large 'middle ground' in which judgements about the relative weights of potential benefits and harms (both to animals and humans, and in terms of safety risks and harms which, potentially, might be caused through inappropriate application of the results of the research) are uncertain, and especially so in the case of genetic engineering, because of the difficulties in predicting the phenotypic effects of manipulations. It is important to examine actual as well as potential benefits and to reassess the benefits as work progresses. Judgements can also depend on the perspective from which the question is asked. For example, people's judgements about the necessity to use animals in medical research can depend on whether or not they, or someone close to them, actually suffers from the disease or condition in question. In this context, there is value in widening the process of ethical review, to bring a range of perspectives to bear on such issues. In the UK, the possibility of lay representation on local ethical review processes for animal research (see 12) is a step in this direction - providing a wider perspective, which will act as an adjunct to the expertise and legal authority of the Home Office inspectorate.

- Possible refinements?

Aside from the potential benefits of the research itself, it is possible that the use of genetically modified mice might result in refinements in animal use - although, overall, any such improvements will need to be balanced against the potential animal welfare problems already outlined.

For example:

- Increasing use of non-human primates?

An area of special concern within biomedical research generally is the use of non-human primates. Some recent developments related to the use of genetic modification raise the possibility that work on non-human primates might increase.

Although there is room for debate about the relative capacities for suffering of the different species of non-human primate, and their capacities when compared with other species (such as mice, or pigs, for example), it is widely acknowledged that it is difficult to satisfy the welfare requirements of non-human primates in the laboratory and thus, that the potential for animal suffering is increased. In addition, some species are only available in the wild and their capture and transport can impose severe stress, as well as a threat to the natural population. All of these considerations need to be taken into account when evaluating the need to use non-human primates (the Boyd Group is currently examining this area).

3.4.2 Xenotransplantation

In the UK, research aimed at developing xenotransplantation involves genetically modified pigs as sources of organs, and some use of non-human primates as recipients. There is much on-going debate about the issues posed by such uses of animals, and this broad area is outside the scope of this report. The issues are explored in recent reports from the Nuffield Council on Bioethics (16), the UK Government Advisory Group on the Ethics of Xenotransplantation (17), the United Kingdom Interim Regulatory Authority on Xenotransplantation (UKXIRA - 18) and the British Union for the Abolition of Vivisection with Compassion in World Farming (13).

3.4.3 Production of pharmaceutically important proteins

Sheep, cattle and goats have all been modified to produce pharmaceutically important proteins for human use. Although it is sometimes possible to use alternative means of producing such proteins, this is not always the case. Most pharmaceutical proteins are needed in large quantities that would be prohibitively expensive to produce by large-scale culture of human cells. Transgenic bacteria, plants and animals provide alternative approaches to overcoming the problem of scale, though often only the use of animals can ensure appropriate biological activity. Alpha-1-antitrypsin (AAT), for example, is required for the treatment of lung diseases such as emphysema and cystic fibrosis. This protein is normally produced in the liver. AAT can be produced in transgenic plants but the product does not have carbohydrate groups which would normally be added in the liver, and it is removed from the bloodstream about 50 times as rapidly as the natural protein. Genetically modified animals that secrete the human protein into their milk are therefore often the only way of producing sufficient quantities of biologically active proteins at an affordable price.

3.4.4 Increasing productivity in farm animals

As noted, at the time of writing there is currently no work in the UK aimed at increasing productivity in farm animals by genetic modification, though selective breeding programmes are directed at achieving the same aim.

The production of genetically modified animals with the sole objective of increasing productivity by enhancing growth rate, or related factors such as muscling, is an area which deserves critical attention. This is due to the severe welfare problems which have been encountered in the past, and also because the benefits arising from such work are generally perceived as low. Ethical review of proposals to undertake such work should take into account the scale of potential welfare problems to the animals concerned, based on previous experiences; the likelihood that such adverse welfare effects will arise in the new work; and how they are to be avoided. It should be remembered that the welfare of some farm animals may already be compromised because they have been bred to 'over produce', and genetically engineering such animals to boost their productivity still further is likely to lead to more animal suffering. In large-scale production and long-term use of genetically modified animals in agriculture, welfare-negative effects caused by genetic modification should not be tolerated, and every effort should be made to minimise such effects. The onus should be on the creators of such animals to prove, under practical circumstances, that welfare is not compromised at any stage during the animal's life.

 

4 CONCLUSIONS

4.1 Fundamental moral objections to genetic modification of animals

Members of the Boyd Group differ in their fundamental moral perspectives on genetic modification of animals. For some the fundamental moral objections are sufficient to persuade them that such work should be severely limited, or abandoned altogether. The consequences for animal welfare, moreover, may be judged so detrimental that the benefits of using such animals can never (or only in the most exceptional cases) outweigh the harms.

For others, the fundamental objections do not, in themselves, provide sufficient reason for avoiding research involving the genetic manipulation of animals, although the majority believe that such concerns give pause, and should be addressed, since perceptions of what is morally acceptable are contestable and can change. At a time of rapid scientific change, it is particularly important to listen to all reasoned arguments that highlight areas of ethical concern.

4.2 Concerns about the consequences of genetic modification of animals

Whatever their fundamental moral position, members of the Boyd Group are agreed that whenever animals are genetically modified and used in science, there should be careful, detailed and critical scrutiny of the consequences of that use, and serious, honest, reflection on the need to use animals at all. This effort should involve everyone associated with the use of genetically modified animals - researchers, funding bodies, the institutional ethical review process, journal editors and those who care for the animals. In addition, it is important to encourage wider public discussion leading to greater understanding of the uses of genetically modified animals and of genetic engineering generally.

The Boyd Group's discussions have focussed on the consequences for animal welfare and on the necessity to produce and use genetically modified animals. It is noted that such work can raise further controversial issues - such as those posed by cloning and patenting genetically modified animals - but these are outside the scope of this paper.

4.2.1 Animal welfare

There is a need for more detailed analysis of the welfare problems (including mortality rates and ages at which death occurs) caused during the production of genetically modified animals.

Directly modifying an animal's genetic material can produce unpredictable, wide-ranging effects, and thus the potential harms and benefits of such procedures are often uncertain. It is therefore especially important that the justification for the work is reassessed as it progresses. To assist in this, the welfare effects of genetic manipulations should be documented in as much detail as possible and efforts should be made to assess success rates in achieving desired phenotypes.

In particular, there is a need for greater commitment to monitoring, collecting and reporting data on adverse/side effects of genetic manipulations. Good practice should be followed, in that adverse effects should be looked for actively and data gathering should involve those responsible for the husbandry of the animals. Welfare problems should be recorded in databases on the characteristics of genetically modified animals, journals should require scientists reporting novel genetic manipulations to document fully the effects on the animals of the procedures. Reporting should include aspects such as deaths in utero occurring during production of genetically modified animals, as well as adverse effects experienced by the resulting animals. The latter should include any morbidity or mortality, changes in health status, changes in weight/growth of the animals, behavioural changes, changes in breeding success, and results of post mortem examinations of gross morphology.

A utilitarian justification for producing and using genetically modified animals must also take into account potential risks to humans and other animals, as well as to the wider environment. While this is a major concern of regulatory bodies, these vary in scope and efficacy between countries, and much more research on safety aspects is needed to inform their decisions.

In recent years, there has been a rapid rise in the production and use of genetically modified animals. The British Home Office statistics should include more information on the scale of the different uses of genetically modified animals, and the extent to which welfare is compromised.

4.2.2 Necessity to use genetically modified animals

A range of potential benefits has been derived, or is sought, from genetic modification of animals. Case-by-case judgements about the necessity to use genetically modified animals must take into account all the various potential harms (both to animals and humans, and in terms of safety risks and harms which potentially might be caused through inappropriate application of the results of the research) and benefits of the work. Such judgements, however, are difficult, and especially so in the case of genetic modification because of the uncertainties involved. Better documentation of the effects of manipulations, as outlined above, should help in informing such judgements. The judgements also depend on the perspective from which the question is asked, and in this context there is value in widening the process of ethical review, to bring a range of perspectives to bear.

The use of genetic modification to increase productivity in farm animals by enhancing growth rate, or related factors such as muscling, is particularly controversial. In large-scale production and long-term use of genetically modified animals in agriculture, welfare-negative effects caused by genetic modification should not be tolerated, and every effort should be made to minimise such effects. The onus should be on the creators of such animals to prove, under practical circumstances, that welfare is not compromised at any stage during the animal's life.

 

NOTES

  1. The terms 'modification' and 'engineering' have been used interchangeably, although their nuances vary. In particular, the term 'engineering' implies a precision that cannot yet be achieved in such techniques and also that the goal is 'production', which is not always the case.

  2. Such points are raised, for example, in an open letter to the UK Government from the British Union for the Abolition of Vivisection and Compassion in World Farming, calling for a ban on all animal genetic engineering. We found the petition a useful focus in our discussions.

  3. As noted earlier, these data include animals conventionally bred from genetically modified stock as well as those used in research. The number of animals bred from genetically modified stock, but not used in research or testing procedures, has increased by 66%; whereas the number of animals used in fundamental and applied studies has increased by 61% over the period 1995-7.

 

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