SHAPING GENES:

Ethics, Law and Science of Using New Genetic Technology in Medicine and Agriculture

Darryl R. J. Macer, Ph.D. Eubios Ethics Institute 1990


Copyright1990, Darryl R. J. Macer. All commercial rights reserved. This publication may be reproduced for limited educational or academic use, however please enquire with the author.

6. Animal Rights


pp.96-108 in Shaping Genes: Ethics, Law and Science of Using New Genetic Technology in Medicine and Agriculture, D.R.J. Macer (Eubios Ethics Institute, 1990).
Making New Strains of Animal

Historically, mankind has developed new breeds of animals displaying specific characteristics. Most of these animals have been for agricultural use, but recently many have been made for biomedical research. Genetically engineered animals are becoming the preferred source of experimental animals. The growing number of transgenic animals described in recent scientific papers, serve to illustrate the rapid developments. Scientists prefer to use standardised animal strains for experiments, and in the pursuit of knowledge they want to study the affects of genes on whole animals. Only by studying the complex animal systems will the effects of altering the genes be seen in transgenic animals, and be understood. Many mice strains have been used for several decades in laboratory experiments, so the concept itself is not novel. New strains of animals that are diseased, and feel more pain, have been developed and the question has to be asked, whether it is right to breed them.

New strains of mice, such as those deficient in the enzyme HPRT (Hopper et al. 1987, Kuehn et al. 1987), have been made, when these embryonic stem (ES) cells introduced to the embryo enter the germline of the animal (see chapter 7). Recently, a new method which can potentially select ES cells with any new genetic manipulation has been developed, so that any isolated gene could be inserted (Mansour et al. 1988). Many mutations have been made in different genes, and the results can be seen in the resulting diseased animals (Capecchi 1989). Many mutations can be tested simultaneously, up to 20-50 retroviral vectors per cell can be introduced into ES cells and used to create germline chimeric animals. Most work has been done in mice (Jackson 1988). Evans and Foster presented the results of 57 different insertions in July 1988, and more are continually being made (Evans & Foster 1988). New mice such as the first female mouse with XY sex chromosomes have been reported. These mice were made after they set up genetic screening affecting sex determination. Each mouse was mosaic in the germline for ES cell derivatives and up to four independently segregating patterns of retroviral insertion were seen. With the average copy number of 12 retroviral vectors used per ES cell, it is theoretically possible to screen for 48 insertions per chimaera made (Lowell-Badge & Robertson 1988). This has resulted in the generation of new strains of animals.

Animals can be made as experimental models of human disease. For example, the first mice strains that are deficient in an enzyme HPRT were made as potential animal models for the human disease Lesch-Nyhan disease (a rare disease, in which the sufferers start to eat their own flesh). Another example is the insertion of a human gene for apolipoprotein CIII in mice, as a model of the human disease hypertriglyceridemia (Ito et al. 1990). This condition is common in people with premature coronary heart disease, and making a mouse model will be useful for learning more about the role of this gene in that. Other animals have been made to study the effects of different possible cancer-forming genes and genes involved in development, and they do have many benefits for medical research.

Drugs for use against AIDS are being tested in mice with a human immune system. The mice were bred with a deficiency called "severe combined immune deficiency" and are abbreviated SCID-hu mice (the "hu" stands for human tissue). SCID-mice are being used for testing the effects of different gene insertions (Bosma et al. 1989). The mice strain is genetically devoid of any immune defences, so when human tissue (usually the thymus tissue which contains immune cells) is implanted the mice respond as if human. Researchers are using these mice as living laboratories to study how the AIDS virus affects the human immune system. This may sound extreme, but considering that the only other animal model for AIDS is a chimpanzee, it is preferable at least to that option.

The ethics of some of this work is challenging in the context of making very unusual and often diseased animals, though medical researchers justify this on the application of the research to untreatable human diseases. These problems are not new in themselves, but the rapidity of change and the types of changes that are possible make it essential to look at the possibilities. With the techniques used for fusing of blastomeres, egg cells and ES cell lines, it may soon be possible to make clones from these cell lines via cell fusion. Eventually one can envisage the development of not just an ES cell line but an independent blastomeric one. There are ES cell lines for mice, hamster (Capecchi 1989), sheep, pigs and work on ES cell lines for other animals is well advanced. Chimeric sheep, goats and cattle have been born. There are teratocarcinoma-derived cell lines for humans (Engstrom et al. 1985, Graham et al. 1987), and unproven ES cell lines for humans (to prove that they are real ES cell lines requires their use in making chimeric animals).

As we have gathered from some of the examples of animals altered by genetic engineering, there are major changes possible in animal characteristics and even category. Conventional animal breeding dramatically illustrates the variety of dogs that we have accepted. There is a great deal of difference between the largest and the smallest dogs, and between different breeds of cattle or horses. Nature itself is full of variety, and the selection of different characteristics in domestic animals has relied on this variety. There has been increasing use of the new technology to increase agricultural production by undertaking such things as altering genes in breeding, or altering the environment as in battery farming. However, there is a point beyond which it is unethical to use animals as a means to an end.

The goals of genetic manipulation must be carefully chosen. Both increased productivity and concerns about animal welfare will remain the most important factors. The size of food animals may be able to be controlled, and rapid growth and maturation are qualities that may be desired for economy of production. Other animals are being designed to become faster growing, or have other characteristics that may increase financial returns, such as disease resistance. The ethical concerns vary with the genes desired, and many people accept the use of gene transfer by conventional animal breeding. If disease resistance is conferred this might be seen as desirable. But what about the alteration of animals growth rates? If a gene can be inserted so that animals do not feel pain from experimental use, should this be done, so researchers can use those animals in experiments? Or is it unethical to alter such fundamental feelings, as pain, which is of physiological value to animals? The boundary to the genetic manipulations used on farm animals is going to be difficult to decide, and may be different in different cultures.


Ethical Limits of Animal Use

The animal welfare movement of modern times was lead by Christians during the last century, especially in Britain, but during the last two decades there have been extremists which have led the public campaigns and have even began terrorist activities (Philp 1990). We all should be concerned about animal welfare and be involved if we see abuse, but in perspective to other problems. There are a variety of ways of looking at animals, it is important to compare them briefly. We must examine the status of animals in light of what we can reason about them, this includes any new scientific knowledge which may elevate the status of animals. Recent biological knowledge has shown that higher animals can exercise free choice and some can learn to count (McGonigle 1985), and this should change the way we regard them (Gaffney 1986). It means that if we do use them we treat them with more respect, not just pity, but mature compassion (Bowker 1986).

Secular philosophers have had to concentrate on different ways of claiming animal rights. They say that since all life evolved, the chief division of life is between plants and animals, man is only one of the animals. Other animals should possess equal rights to humans as they are part of the same class. However, it is clear if you examine animals that there are many types.

Another approach has been to look for characteristics that have been claimed to make humans higher than animals. As we learn more of animals we can critically examine these characteristics, and it is clear that animals have been found that share many of these with humans. I talk of human as a species, rather than as individuals, on the criteria that all humans are of equal value. If we use this approach then we would give animals potentially the same rights if they have equal capacity for the characteristic chosen. Intelligence and intellect can be distinguished, in the sense that intelligence is a relative quality. Language ability is one sign of intellect, but it is very difficult to estimate the language ability of animals who use very different methods. One way is to examine the complexity of the language, which would eliminate most animals from being close to humans, but there would still be doubts over some. It has been found that chimpanzees can be taught sign language, and talk to humans in it, but only to the extent of composing two or three sentence replies. This represents a stage equivalent to a human baby learning to talk, before they can start to actually make longer sentences. Chimpanzees have not composed long sentences, but their must still remain enough doubt about their ability to give them certain rights.

It could be argued that there is sufficient intelligence shown by them to prevent their use by humans, and that would be consistent with what we know of their brain structure, behaviour, and the doubts on early views that placed them with "lower" animals, certainly more consistent than the widespread use of chimpanzees, gorillas, orangutans and other higher primates in scientific research. Though during the last few years, with added pressure due to the possibility of extinction of these animals, there has been much less research use of them. Dolphins are another species whose intelligence and rationality is sufficient to protect them from use in destructive research. There status is sufficiently high to prevent their destructive use, though their is still a case for behavioural research to try to understand them if it is well controlled and humane. Their behaviour is beyond that of reflex behaviour or the unthinking genetic level of response seen in lower animals. In a following section we will consider the major argument used by utilitarians against animal research, that of promoting pleasure and avoiding pain.

Another of the major criteria has been the universal human possession of a uniquely moral will and the autonomy inherent in this. Animals lack this capacity for free moral judgement, and if they are incapable of exercising, or responding, to moral claims then they do not possess the same sort of rights as humans do. We can talk of humans as a species, rather then talking of the few exceptions who do exhibit this characteristic. We still have duties to animals, but not the same that we owe to humans. The grounds of our duties are not based on giving them equal value to humans and the corresponding rights, but they are of lower valuation. If we owe them certain duties we can say that they possess certain rights in the same way that we use the word "rights" to speak of the duties we owe other beings.

Religious Views of Animal Status

The motive behind the use of animals alters the morality of their use in some religions and in some philosophical systems. Animal sacrifice for worship is used in Islam, but they would generally condemn scientific research or battery farming. Vivisection is allowed under circumstances where there is no pain or disfigurement and if other animals benefit. The use of animals in science is under the same moral codes as applied to humans. Even though the animals possess a lower consciousness, Islam says animals know their own mode of prayer and psalm, a voluntary act of praise (Masri 1986). The killing of any breathing beings, except for food or religious sacrifice, is high on the list of deadly sins. Hindus, Jains and Buddhist believe that we will be reborn as another living animal, which creates their bond of caring and compassion for animals (Bowker 1986). So they will reject animal sacrifice, even though the sacrifice of an animal won't kill what is essential, in the reality, the soul, of that animal.

Like other religions, Christianity agrees that the scriptures and traditions may not have so much as a concept of animal rights, but that animals do have valid claims upon us. It is an issue of human responsibility which we cannot ignore. Different religions have different accounts of what constitutes animal nature. Animals cannot be viewed simply as expendable raw materials for our designs (Linzey 1986), they do not exist simply to serve us, the doctrine of creation is opposed to anthropocentric notions.

The Bible often mentions animals, as Israel was an agricultural community. God owns everything of creation, including all our cattle (Ps. 50:10) and He cares for them all (Gen. 8:17, 9:4,10; Ex. 23:5; Deut. 12:23, 25:4; Num. 22:32; Prov. 12:10; Ps. 36:7, 104:10-11, 145:9,15-16, 147:9; Job 38:26-27,41; Jonah 4:11). God is not even careless of birds (Matt. 6:25, 10:29). God's mercies are over all His works (Ps. 145:9), and animals should also rest on the sabbath (Ex. 23:12; Deut. 5:14), and should be fed first, before the farmer (Deut. 11:15; Num. 20:8). Animals can be eaten and farmed (Gen. 9:3; Deut. 12:20), as man has dominion over every living thing (Gen. 1:28), the fear of man being in the animals (Gen. 9:1-2). The use of animal sacrifices (Lev. 22:24) does not mean animals should be sacrificed for the selfish pursuits of man, the practise of animal sacrifice was to bring God into the focus of men's hearts in place of their own selfish desires, and was not necessary after the birth of Christ. We must respect animal life, some believe this is why that Jews could not eat flesh with its blood (Gen. 9:4), though that may have been more a recommendation applying to health in avoiding eating contaminated meat.

In the New Testament we see some of the verses of the Old Testament being used in an allegorical way, not directly applied. The two most important factors are respect for God's creation and love, which is the fulfilling of the law (Rom. 13:10). There is a certain unity of life which makes us respect animals. Early Christian theologians such as Aquinas regarded animals as irrational creatures that weren't directly possible of human friendships. However the loving concern to preserve irrational creatures may be both motivated by their utility to man and being of honour to God. The tradition of the Roman Catholic church is to regard animals as means to human ends, and the moral objections to cruelty on animals are more concerned with fear that those inflicting pain will contract habits of cruelty. Death is not the greatest evil that we can imagine, and there may be more important things in life than living by the easiest means. Christians should see things in terms of the Kingdom of God, and love applies to all creatures of the earth. The attitude of St. Francis, to talk of sister cows or brother dog, is a picture which we should not forget.

Speciesism is a word used to describe the view that man is the only species with protectable "rights" and that animals do not have any rights (Singer 1976). There have been several famous proponents of this view, a couple of the more fundamental were Aquinas and Descartes. The Bible has often been criticised by nonChristian animal welfarists because of its assertion that man is uniquely made in the image of God, has dominion over the rest of creation including the permission to kill and to eat animals. Most people are speciesists, and would not consider the claim that we should regard animals the same as humans as quite sensible and even obvious (Cohen 1986). There are many morally relevant differences between humans and animals. However, the belief that man is unique does not mean that animals have no rights, that we do not owe them duties. There are certainly ethical codes in most religions, though they are often not followed.

Philosophical Views of Animal Status

One of the most important criteria in judging the use of animals by humans is that of avoiding the infliction of pain. The Oxford Dictionary would define pain as "suffering or distress of body (from injury or disease) or mind." Philosophers have distinguished pain from "suffering." Bentham (1789) relies on a notion of animal suffering rather than just pain. Regan (1983) defines suffering as prolonged pain of a certain intensity, and argues that no individual can suffer who is incapable of experiencing pain. The capacity for suffering and/or enjoyment has been described as a prerequisite for having any interests (Singer 1976). Individuals can experience pain from suffering of the body or mind. This type of criteria is prevalent in utilitarianism.

Judging pain is subjective, there are different categories of pain such as acute, periodic or chronic and the pain threshold varies between different beings, people, cultures and circumstances. There are no major biological reasons for the idea that human pain is intrinsically more intense than animal pain (Iggo 1983). There are parallels in the way animals and humans respond. Many of the neurotransmitters are similar between higher animals and humans. It is possible that animals do have a different quality of "pain", as the frontal region of the cerebral cortex of humans is thought to be involved in feelings of anxiety, apprehension and suffering components of pain. This region is much smaller in animals, and if it is surgically treated in humans it can make them indifferent to pain. There are differences seen in the types of pain receptors, some respond to mechanical stimuli, some to noxious heat or irritant chemicals, and some to severe cold. Studies in human fetuses have shown the early appearance of sensation before pain receptors in the skin are developed. In human fetuses the myelinated fibres develop much later than the nonmyelinated fibres, so it is possible they feel more pain at this stage, then they do later on, or when born (McCullagh 1987).

If we look at the boundary beyond which organisms feel pain, we could put the dead, depending on our criteria of death. We could probably put the unconscious, including those under general anaesthetic. We could say that beings under local anaesthetic may not feel physical pain, but could feel anxiety, as is felt if one being is watching another suffer pain or what appears to produce pain. This capacity is part of being sentient, the capacity of a being to perceive, or understand, what they can sense (see or hear or feel). Many of the motor reactions to noxious stimuli can occur in unconscious beings, some extending from the brain stem, including vocalisation.

We may all agree that animals can suffer, but the question is how much does it matter? There may be a choice between human welfare and the suffering of nonhuman animals. Many people accept that all humans are equal in moral status, and all humans are of superior moral status to nonhuman animals. From these two moral principles they put human welfare ahead of animal suffering. Peter Singer (1976) argues that these two moral principles cannot be defended within the terms of a nonreligious approach to ethics. He concludes that there is no rational ethical justification for always putting human suffering ahead of that of nonhuman animals. He argues that "if we are considering public policy in a pluralistic society, we should not take a particular religious outlook as the basis for our laws" (Singer 1990). While this is true, it does not imply that we need to take rational utilitarian philosophy as the basis for public policy either. Many different people's cultural and religious views are more consistent with human beings having a higher moral status than animals.

However, it is still important to summarise his argument, as it does have consequences for the way we regard animals, and we should improve their treatment. The problem with saying that humans are of higher moral status than animals is that while the human species may have higher mental capacities than animals, not all people do. The word speciesism reflects this view, which has its roots in the Judeo-Christian belief that humans are made in the image of God. However, in rational philosophy we cannot prove this. We should focus on the individual when considering ethics, which has been a focus of the movements against sexual or racial discrimination also. He argues that we should consider all beings who can suffer in our moral considerations, regardless of species (Singer 1990). However, Singer would still not say that the deaths of animals are equal to the deaths of all humans, as there is an additional factor of the awareness of the future that humans have, which most animals do not have. To kill a human being destroys all the plans that they have made, a feature of humans. He also acknowledges the importance of extrinsic moral factors, such the feelings of family members if one dies (though this is shared with some other familial mammals). At the practical level, the feeling of pain is the first major guiding principle for animal treatment. The second is that we should not kill some animals, if they have self-awareness such as higher apes, and probably other animals such as dolphins. We do need to consider the findings of animal studies on the level of self-awareness that some may possess.

There are already many painless experiments performed on animals, and anaesthetics are often used if pain is involved (Frey 1983). Government regulations on animal use and experimentation emphasize the importance placed on avoidance of pain, and regulations limit the amount of animal suffering and experimentation. Many believe that there is a world of difference between experimentation that does and does not involve pain, including possible suffering through confinement in small cages (Sprigge 1983). There are some very efficient pain-killers, some of which can be used for long term pain. There are chemical nerve blocks which can be used to block pain from particular areas of the body for several months, or physical methods. Animals can be made to be like vegetables by removing the pain pathway. Animals may be perceived as feeling less pain, because of their rapid recovery rate from surgery, or the presence of what seem appalling injuries in some animals in the wild that apparently do not sense much pain. However, we do not know how much pain they feel.

While actively producing pain is seen as an evil, sensation of pain is necessary as pain is important in the proper functioning of nervous systems, so feeling pain should not be seen as evil. What is seen as an evil is the production of pain in other beings, or the introduction of disease into other beings. Because pain is a basic sensation we may object to manipulating it permanently out of strains of animals, but what argument would we apply to justify or object to such developments?

If we make animal painless we are depriving them of a beneficial physical awareness. We could imagine beings that could be made with limited sentience, only having the perception needed for basic survival, such as for limited self interest for eating, grooming or avoiding injury. In the extreme case we could consider animals made that enjoy being kept in factory style farms, or that want to be eaten, or are even masochistic. These need not be as futuristic as the talking cow portrayed by Douglas Adams' book (1980). We might talk of degrees of pain that could be removed, such as leaving a protective sensation, but instead of it invoking pain, it could just invoke a reflex so that the being would not do injury to itself. It is possible to alter behaviour by control of certain neurotransmitters, such as oxytocin, which is a memory disruptive agent and has been used to remove active avoidance behaviour in animals, that is the animals do not remember painful experiences. Currently, more control can be made using external agents, however, within the next few years of pain and neurobiological research many transgenic animals will continue to be made. It is very likely that transgenic experiments will be used in pain research. When animals that are painless are produced, which is inevitable, the question will be asked about breeding them.

These type of experiments involve altering the mental requirements of animals to suite our means. We could look at them as beings that would not be able to give their informed consent, though this is never sought from animals or human infants anyway. In fact these futuristic beings could be engineered to give consent. This is not to say that neurobiology is understood now, but it will be in the next decades. The motive is only anthropocentric and the means used are not interested with the life of the animals themselves, however if they did not suffer pain than they could be regarded by many as being better off then beings that do.

If we object to these experiments, we would probably be forced away from arguments based on pain, or preference utilitarianism (Singer 1980), in which sentience, the capacity of a subject for sensation, is the pre-eminent quality on which attitudes towards the treatment of that being by others is based. Some deontologists believe that all creatures capable of suffering, have a general moral right not to be treated cruelly, but this does not preclude their treatment as mere instruments (Feinberg 1980). If we object to these painless animals being made, it may be because we hold religious views according to which we should not "grossly alter the creatures of the earth, or some sort of argument based on it being "unnatural" (Jonas 1966). It could be based on each being having a self, suffering being viewed as the threat to characteristic, worldly related activities which threatens the integrity of the self (Donnelley 1989), as would the removal of sentience. If you don't like the idea of animals being made this way, ask yourself, why not? The Christian view would be that because God gave responsibility to man to look after animals. One must respect other creatures in God's creation and not misuse power (Macer 1990a).

To set out to breed painless animals so that they can then be supposedly used as beings possessing no moral rights is different to the use of "beings" that are born without a brain, anencephalic, or that are painless. There may also be a difference between making a breed of painless animals to using individuals made painless during their ontogeny. An individual that has had some history of feeling pain and is made painless could experience (unless they are made completely nonsentient) either relief or bewilderment. The creation of painless animals in order to make a new class of means for human ends may alter the way we argue about the use of animals. Instead of animals possessing some sort of self integrity, they can be made to be much more the longterm property of humans, not only in commercial terms, or when or how they come into existence, and reproductive choice, but in whether they are sentient animals or a new class of painless animals or "vegemals". Some would argue that this new class would possess the moral status of plants, and they could leave the "normal" animals to roam the pastures, or what is left of the jungles, while using these specially made beings. However, I believe that many would share the view that this would be an unethical use of our power over nature.

It may point to a time when human values, as much as they are regarded by many philosophers as unsound, culturally determined, undefinable feelings, may have a greater place in ethics, either because such creations would be contrary to most people's values, or because of the effect such a creative power would have on our values (Macer 1989). This is a type of view formulated by Kant, in which he said that we have no direct duties to animals, but if we mistreat them it will remove our feelings to humans. However, it does not always follow, as human tyrants have often been devoted to their pets: we do distinguish between animals and humans, and between friends and enemies. It is useful as an argument when others which are usually stronger, do not apply.

It may be possible to make painless animals, so deeper reasons against the abuse of animals must be examined. It will never be sufficient to justify animal use on the sole grounds of these experimental benefits of using them. We could also gain by human experiments. The justification has to lie on animals having a lower status than humans, but it can still be argued that there are justifiable and unjustifiable uses of animals. In fact the number of animals used in research is less than 0.1% of the animals used and killed by humans. In the face of this we could ask whether genetic engineering poses an extra threat to animals, beyond that of other uses of animals. Genetic engineering may in a few examples allow more potential to change the morphology or internal nature of animals, but there may be other uses of animals which are more unethical. Also the animals changed will be used to improve agricultural strains, so will be part of both "markets" for the use of animals. While changing animals internally offers new problems, we still need to work on the external treatment of animals in general.

There are many commercial uses of animals for testing of what could be called luxury products, such as cosmetics. Each company wants to make a slightly different perfume or soap, and may use animal testing. These tests are objectionable for several reasons, the first one being that they are painful; the second that they are argued to be unnecessary, there are alternative ways of testing using toxicity measurements on cell lines, and the products are very similar to those already on the market, so either are safe enough to use, or not necessary. The only reason they are desired is to make a profit for another business. If companies made the results of their testing known then their competitors would not need to repeat them. Alternative methods are being used to avoid animal use. During the last few years there has been increasing use of products not tested on animals, as a result of consumer purchasing choices.

Genetically engineered animals which are very sensitive to carcinogens, can be used as more sensitive "probes" which would dramatically reduce the number of animals used. It is estimated that "Oncomouse" may lead to some tests for chemical carcinogenicity being compressed from three years to three months. If this is realistic, net costs for experimental animals, as well as the total number of animals used in such studies, will dramatically drop. Another reduction in the number of animals used has been brought about by the use of embryo splitting, which should also be increasingly used. When an embryo is split then the individuals made, 2 -8 in number, are clones, genetically identical. If genetically identical animals are used then the number of animals required in a toxicity test is greatly reduced, as the only difference in treatment and response is attributable to the tested drug. If we are realistic and accept that there will be some animal testing, then at least these techniques will reduce the quantity involved perhaps tenfold. There has also been debate on what sources of animals can be used, especially whether stray dogs and cats can be used for experiments. There are many more stray dogs and cats "put down" than there are animals used in experiments. It would seem better to use them than to breed animals to do experiments on. There are many experiments that do not require a precise laboratory strain to be used if an alternative exists. However, there has been much public debate, as people say that animals that have experienced being a pet would find it harder to be in a cage. However, many of these animals would probably receive more loving care in a laboratory than they did in the situation they were in before.

Genetic engineering has been used to make vaccines against animal pests, and to protect animals from disease. These could be argued to actually benefit the animals themselves, so be on the positive side. However, there is some inherent opposition to the creation of diseased animals, which some may justify by their potential to advance to medicine. If humans are born that are diseased and some trace can be made to their cause of injury, if the cause can be proven there may be financial compensation at least, however if we make diseased animals it may obtain acclaim from the scientific community for their benefit to scientific and medical research. In fact, some of these animals do advance medicine, and they may not feel much more pain than they otherwise would, but this certainly does not mean it is always justified. In terms of the quantity of pain endured, there is probably less pain than many animals face in factory-style farming. In fact the facilities for care of animals in science is much better than those conditions found in many farms, partly because of the regulations that apply to animals in laboratories that do not apply to farming. The motive for the use of the two types is different, one is for science the other for food, it is not obvious which is the more ethical use of animals. It could be argued that because we have alternative foodstuffs, from plants, the use of animals in medical research is more justified. However, animal rights activists do not usually picket abattoirs.

That is the issue on a broad scale, but what about the individual animals bred for such testing. In the case of clones, they are the same normal animals. In the case of deliberately diseased animals, such as those that develop cancer very easily, or have physical abnormalities bred into them, the question is whether the means justifies the ends. Do we have the right to the actual use of animals, to create in that way, and to bring them into life at all? Numerous "new" animals have been made. There are those that develop cancer, such as the so-called "Oncomouse" that was patented, and numerous other types of genetically modified animal strains, many in mice (Fox et al. 1989). Another example was the addition of the gene for diptheria toxin to a gene expressed only in one cell type in the pancreas (the elastase gene). The toxin was only produced in such cells, killing all that type of pancreatic cell. It is possible to target particular cell lineages to kill them. This allows the study of the animal without those cells. Some of these animals are made to study the genes involved in development, including what are unique models for cancer research.

There have been transgenic mice made as models of the immune system, and a new area of research will be making models to study the nervous system (Hanahan 1989). Embryonic stem cells are used to make some of these genetic modifications and new strains, and there is much research into the genes that control the developmental process (Gossler et al. 1989). The ES cell lines make it easier to control specific genes, for the study of the disease itself and for gene therapy tests. Another area of much scientific interest is their use in studying development, such as for studies in disruption of homeo-box genes. The making of chimeric animals, such as the geep, has been useful for study of the immunological development of the embryo, and rejection mechanisms. There are also major questions such as the fate of each cell as the embryo tissues develop, and the processes of the immune system in developing self-tolerance. The ES cell lines also offer ways to study many new mutations. They have advantages over other methods of making transgenic animals, in the precision of gene insertion possible by homologous recombination, in the simultaneous screening of mutants. Although at this stage other methods of gene insertion have wider species application, they have been made for several species, so should be possible in others when attempted. Their advantage in agriculture, would be the increased sense of safety, from the precision offered.

Transgenic studies after incorporating growth hormone genes into pigs and sheep have not shown any relation between gene number and expression of genes and growth rate. In fact many of the pigs died within 90 days of birth in the preliminary experiments, with significant problems of lethargy, muscle weakness, incoordination, and susceptibility to stress (Lamming 1988). Most of the transgenic animals did express much more growth hormone, and did have improved weight gain (about 10%), but also had gastric ulcers, dermatitis, nephritis and other major problems. This does illustrate the problems, and until these factors can be removed even if it was economic to use these animals, it would not be ethical if they are going to suffer. Research into new genes and techniques continue (Pursel et al. 1989). There have been pigs made that are not sick, but grow faster.

There have been several surveys about the reason animals are used in medical experiments. The researchers have only begun to realise that they have to publicise the benefits of their projects to counter the strong pressure from the antivivisection lobby (CSA 1989, Loeb 1989). The use of animals in research, or agriculture is based on the use of animals by mankind, since our origins. It assumes we can dominate animals when necessary for the improvement of human living standards. This is based on the starting point that humans are of higher status than animals. If we reject this, then we will probably oppose human uses of animals. There have been considerable numbers of studies done on particular animals, the mouse and the rat are the most common, and should become more so with the higher maintenance costs of larger animals and the lower level of public sympathy for mice or rats. In medicine they have been used for general biology, transplant studies, for risk assessment of potential carcinogens, for human disease models and behavioural studies (Gill et al. 1989). Their use will continue, but substitutes will be found.


Regulations

Animals that are genetically modified will probably come under some type of regulation. In many cases it may be only in regard to the laboratory maintenance or experiments on them, rather than their creation itself. In Britain transgenic animals can now only be made under license from the Health and Safety Executive (Connor 1989). The Committee recommended that the license should cover the breeding of transgenic animals until it can be demonstrated that the progeny are not likely to suffer adverse affects (HSE 1989). The Animals (Scientific Procedures) Act 1986, regulates "any experiment or other scientific procedure applied to a protected animal which may have the effect of causing the animal pain, suffering, distress or lasting harm". This applies to the creation of new varieties made by genetic engineering techniques. It is important to consider the last part of that sentence, "lasting harm", which is a characteristic of animals made as models of human disease.

It is a common misconception that genetic engineering will try to increase the size of animals. In most cases smaller animals are desired as they are cheaper to maintain. Chickens and pigs have become smaller recently (Seidel 1986). What is desired is rapid growth rate, or turnover. This also means that the average age of farm animals will decrease, and this is a trend that has been occurring as younger animals are more efficient, such as egg-laying hens or dairy cattle. In addition to increasing growth rate, other agricultural aims include decreasing water dependence, increasing drug resistance and disease resistance. Some of the effects could be neutral such as controlled increase of size, or altering fat/protein balance, or altering forage requirements, and the quality of products such as eggs or wool, but each case should be examined. Dairy cows in the 1980's produce 2.5 times more milk than those in the 1940's. The use of genetic engineering will be able to more dramatically change the metabolic characteristics of animals.

There has been a very useful evaluation of research procedures, so that only those which are judged to be ethical are pursued. This has saved much animal abuse, and a limit will be reached at which only ethical uses of animals are permitted. The humane treatment of animals requires that if alternatives do exist to obtain a satisfactory result than we use that method. Alternatives involve reducing the number, refinement of procedures so there is less suffering, or replacement of animals (Smith 1988). Alternatives include using in vitro experiments, using cell lines, or embryos of lower status or larvae, or isolated organs, and computer simulation. The urgency of the research needs to be reassessed.

Government regulations that require animal testing of new drugs and compounds need to move with the development of alternatives. Often much animal experimentation is done because of regulations protecting humans from unforseen effects of drugs or new medical therapy. One step is for alternatives to be quickly developed, tested and accepted. Another step is to limit the duplication of commercial products, including pharmaceuticals. There need to be alternatives developed in toxicity testing, which is not only more ethical but more economic (Goldberg & Frazier 1989). In this respect new genetic techniques and embryo manipulation will reduce the number of animals used in vivisection. If we place much higher value on humans than the experimental animals, such as mice or rats, then we will use animals to test drugs to protect humans from any ill-effects (Cohen 1986), but only within limits. It is consistent to use lower organisms if possible, and also to use human volunteers and epidemiological research.

Food animal farms house the vast majority of animals used by humans. The attention given to animal rights by experimental use of animals has also shifted attention to the practise in farming. Principle concerns include confinement of veal calves, pigs and poultry in small cages. There have been several countries which have banned the use of battery caged hens. It has been illegal to make battery cages in Switzerland since 1981, and their use will be illegal from 1992. In Sweden they will be illegal from 1998. There are new rules in the U.S. Department of Agriculture for the care of guinea pigs, hamsters and rabbits, from July 1990. However, the rules have some flexibility, so that laboratories will not need to buy new cages. They can do things, such as build tubes to connect hamster cages so that they are happier, because they can run around. It will be based on the use of performance tests to check if the animals are happy, which could be very hard to judge. These regulations reflect much public objection to practises that are seen to be cruel, and which can be avoided at little extra cost (Nicol & Dawkins 1990). It is still possible to use contained areas for farming, but greater space in required. This may be important in the containment facilities that are given to genetically modified animals, and also reflects the growing influence of animal welfare concerns in different countries.

If society changes its philosophy of animal use it should know the consequences of any change. If people do not want to grow animals for food than they have to eat vegetables. If they do not want to use animals for some medical research than they should not expect such rapid advance in the treatment of disease. There needs to be education about the consequences of altering the way we treat animals. People need to decide how much more they are prepared to pay for better treatment of animals, such as the costs of eliminating battery farming, or the costs in not using new animal treatments that produce cheaper milk or meat such as bovine somatotropin. The consequences on the different communities involved in agriculture of these decisions also needs to be considered, a variety of external factors, some of which will be discussed later.


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