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.

15. Human Genetic Engineering


pp.295-324 in Shaping Genes: Ethics, Law and Science of Using New Genetic Technology in Medicine and Agriculture, D.R.J. Macer (Eubios Ethics Institute, 1990).
Of the many fears over the future abuse of science, the most sensitive area is the changes that affect the inner constitution of humans. There has been much written considering the fears of human genetic engineering, and it still arouses strong passions. The technical ability has developed to a point where certain types of "genetic engineering" are possible, which makes the topic no longer one of mere speculation, but one of immediate importance in health law and ethics.

The term "genetic engineering" has caught the public imagination in a negative way, and by using it there will be a biased view. I use it in preference to another biased term, genetic manipulation. Genetic engineering is the most applicable word to the topic of this chapter, so I will use it, as I also previously used the word eugenics. The question of eugenics was central to chapter 6, but this chapter will consider more positive eugenics. A common association with genetic engineering is what people call "the Frankenstein thing" (Rollin 1986). Many people have a strong reaction to the talk of genetics whether it be on animals or talked of in humans. A major part of this response, that something is unnatural or unusual or extraordinary is not a genuine moral issue. What is the most important moral issue, whether it be regarding animals or humans, and the theme of the original Frankenstein story, is the plight of the being who is altered. This should be seen throughout the techniques.

There are arguments that are commonly used in support or against genetic engineering. In favour of genetic engineering is utilitarian thinking. Although there will be risks for individuals the goal of the application of these techniques will be to aid human beings, in reducing genetic disease and its affects, and possibly improving the human race (Brody 1981). We are rational beings and we should take advantage of the chances used to apply our rationality to the control of something so important as the generation of children, and to agriculture and environmental modification. We have allowed many people that have genetic disease to live, and so have exposed the human race to genetic decay, for example diseases like diabetes are increasing. This is seen as a bad affect on the human gene pool, and something to counter.

Against genetic engineering are arguments such as it is unnatural. We replace natural procreation of human beings. We will always be unsure of the longterm affects of our manipulations, and they may cause harm. We are still ignorant of the mechanism of gene action, and living systems are very complex. The misuses of genetics in the past, illustrated how bad values may be propagated, and these techniques could be abused in the future. There are more important uses to put our resources into than into genetic engineering. Some object by saying that the means may be immoral, such as procreation independent of natural processes, and the loss of embryos. Although much work in genetic engineering has involved microorganisms and recently plants and animals, much of the anxiety concerns extrapolations to humans. All of nature is important, especially with an ecological awareness, but because of the fears relating to humans, we will particularly look at issues that relate to human beings in this chapter.

"We Should Not Play God " is a very common phrase, but its connection with genetic engineering is not as clear as opponents claim, as discussed in chapter 3. For one thing, if we consider "God" to mean we should not intervene in the processes of nature, as it often does, then it is wrong, as this philosophy rejects modern life altogether, along with medicine and most agriculture also. Another slogan has been "It's not good to fool Mother Nature", however it is quite good to fool nature when treating disease. While there may be a boundary to our intervention in Nature, it is not based on the idea that it is intrinsically wrong to use or change nature, including using genetic engineering. In most religion's the pursuit of health and food of some sort are essential goods.

Related is the question of whether we are creating new life forms. This is somewhat misleading, as while we can produce organisms with new characteristics there is already a long history of human beings directly and indirectly producing these. We have breached species barriers often in agriculture. There are natural mechanisms to transfer DNA between not just species but entire kingdoms of living organisms, such as from yeast and eucaryotes and bacteria. Our recent knowledge suggests that it is less unnatural then we first thought, which also decreases any objection to the modification of living organisms based on this type of argument .


Genetic Selection

The techniques available for aiding reproduction make genetic selection more powerful than in the past when infanticide or sterilisation or selected mating were the only alternatives. We have considered the question of mass screening of potential parents, in order to detect any disease-causing genes they carry before reproduction. People could voluntarily refrain from reproducing or alter their marriage plans if they carry a designated disease. When one of the couple carries a serious genetic defect IVF or artificial insemination, by donated gametes, could be considered. However, there is a "slippery-slope" from the decision of using gametes donated by an anonymous donor, to the case of using gametes selected from people of chosen "quality". There have been babies born from women using AID to conceive their eggs with sperm from Nobel prize-winning scientists. It is also possible that eggs will be donated. Ethically these two alternatives are similar. The limited resources for IVF may mean that IVF is not used currently except for helping the most needy cases.

One of the major arguments against the specific selection of gametes from a donor because of their desirable trait(s) is that we would be aiming more at the biological quality rather than the children themselves. There is a difference between choosing a donor because they are especially intelligent, or good-looking, and choosing any acceptable donor for having children. Because people can use gametes from a person that does not carry a serious genetic defect, does not mean they should choose their favourite scientist or politician, as a donor. There are sperm-banks already being built up, so that this is possible, and some are commercially operated. Verbal genetic history's of sperm donors are made to try to exclude donors that have some genetic diseases. A physical examination and laboratory testing is recommended by the American Fertility Society. As new techniques arise, there will be many more diseases which can be screened against. Both verbal and cytogenetic screening has also been used in the French CEGOS AID services (Selva et al. 1986). It is ethical to ensure as far as possible that possible donor sperm and eggs do not carry a genetic disease. Currently the burden is on the practitioners and subjects of such studies, but in a sufficiently dictatorial society this could be unethically abused. Since however many other scientific techniques could be abused, this may not justify not using it.

The wrongness in this is not so much the use of good donors for sperm, but the presumed relationship between the quality of the child to be (which may have a higher I.Q. or quality than normal) and its status as a human being makes people consumer products. The Nobel Prize-winning scientist Herman Muller concentrated his efforts on voluntary positive eugenics, founding a term "Germinal Choice", which he thought was an extension to birth control used in reproductive choice. The major method for this was artificial insemination using donor sperm (AID), but instead of the donors being anonymous he advocated using selected donors (Muller 1935). The number of children born by AID in USA is large (CIBA 1973), with at least 300,00 births, so it would be a major selection if employed. The characters he chose in a donor were good health, high intelligence and socially responsible cooperativeness. Some of these characters changed with time, as did the list of his examples of men, at one stage including Lenin, but during the Cold War this changed. The so-called right to procreate, may lead to procreative autonomy, the right to take positive steps to enhance the possibility that offspring will have desired characteristics (Robertson 1983), is a rephrasing of Muller's idea of germinal choice (Muller 1960).

While small scale AID to overcome infertility might not have any detrimental effect on general human reproduction or procreation, large scale attempts at genetic manipulation pose a potential threat to society. This is not like the use of negative eugenics by genetic screening for disease carrying genes, but would have a more dramatic effect on our reproductive patterns, especially in those countries where random mating occurs. We do not know the longterm effects of positive gene selection. There have been strong protests against the use of genetic engineering to alter the germline of humans, such as those led by activist Jeremy Rifkin, because of the fear that they will be used for eugenic ends (Norman 1983, Rifkin 1983). Selective mating for genes is very different to the selective mating that occurs for personalities, or familial social status. There are a few examples of restricted mating patterns among royal families, which are generally recognised as being detrimental to the children's health. This highlight's a need to use gametes from a single donor only a limited number of times, to avoid the possibility of half brother-sister marriages.

IVF, egg donation, AIH, AID, or surrogate motherhood which can enable infertile parents to have children, can also be used for eugenic selection (Glass 1972). While there may be many cases in which these new reproductive technologies may be used for their primary purpose, there are additional ethical problems associated with their application to positive genetic selection. We considered the ethics of using extramarital gametes in chapter 11. The techniques of AID and embryo transfer might be ethical in some circumstances. The choice of the donor and the donor's anonymity is one of the problems of the technique. It is ethical to check that the gametes are not carrying some genetic disease, and is unethical to use them without checking if the screening capacity exists, however, it is a very different case when the couple are carrying a high expectancy of having a child with the donor's "excellent genes". Any positive selection scheme would also have the associated problems of high parental expectancy of good genetic children, the child-supermarket problems.

Antanasio (1986) considered the example of a new company that discovers a novel drug that can be used to develop stronger, more intelligent human beings. However, this drug is very expensive, and limited to a few cases. If the government banned the use of this drug would it violate the liberty of people to use it? Banning this treatment would not interfere with reproductive freedom, as the parents can still have a child using normal methods (or nonselected sperm for AID). It would be consistent with the idea of freedom to chose children's education, but it is not inconsistent to ban this drug as the decisions are at different stages of life. The children do have liberty interests, as argued in chapter 13, as genetic freedom. While we may promote the free-will or liberty of parents, we may restrict the "freewill" of the children who must conform to the expected pattern.

It would not be ethical to use donated gametes when the parent's own gametes are fertile and do not carry an untreatable genetic disease, because it is interfering unnecessarily with normal reproduction. It is possible to purchase sperm from donors of known characteristics in the USA. The parents may desire the donor's physical characteristics to be similar to the husband, so that it is difficult to notice that the child is from extramarital gametes. This could be ethical if it is to protect the child until they are mature enough to be told of their genetic origin, however I do not consider it ethical to hold the child permanently in a deceitful relationship. Sperm banks, can also carry information on the educational and intellectual level of the donor, which can aid selection of gametes from donors of higher intelligence. It could be ethical if the parents do not expect their child to be very clever, as the children will probably not be, but if they are expecting a very clever child then proper counseling is required and it is very doubtful whether this sort of selection is ethical.


Germ-line Gene Therapy

Somatic cell gene therapy concerns only the individual treated, assuming it is safe, and is up to personal self-determination, or traditional forms of consent giving. The replacement of a defective gene by a normal one by somatic cell gene therapy still leaves the problem that we need to modify our genotype to improve the situation for long term. However, germline gene therapy involves all future offspring in a more direct way. The immediate concern must be whether it is safe. There may be harmful effects in the future generations. We have the ability to transfer genes, but we still lack the knowledge of the resultant gene transfer. This is especially so for a future person when undergoing full development from an embryo to adult, when different genes and regulatory sequences are used. Researchers should use experience combined with imagination of possible consequences. There are also new genetic techniques for positive gene manipulation. These would allow the treatment of sufferers of genetic disease in extended ways to our already major treatment of the symptoms of genetic disease in medicine.

Although germline gene therapy is not yet safe enough for use, we must consider technology before it is ready to be used, when it has such major consequences. In the last decade discussion of genetic engineering and its implications was often shrugged off, using those reasons, however, we have seen such rapid developments in technology we cannot predict when pressure will grow to use this technique. Other issues may be more pressing at the moment, such as provision of genetic screening services and privacy of genetic information, but the long term nature of genetic manipulation of the human germline must also be discussed.

Techniques for Germ-line Alteration

There are several alternative strategies for alteration of the germ-line. Most commentators have concentrated their attention on those techniques which are able to provide precise gene replacement or insertion. While this is the ideal case, and will no doubt become possible, we should rather concentrate on the underlying goal. The goal is to obtain normal gene expression that is safe to an individual who would not otherwise be healthy. There must be no negative side effects. While this may be obtained by precise gene replacement, it might also be obtained in other ways.

There are two stages at which the human germ-line may be altered. One is at the level of the germ-cells, eggs and sperm, which could be altered in vivo or in vitro. The other stage is at the embryonic stage, which would be in vitro. I will consider the case as being one which is aimed at correction of a genetic disease, though the techniques are only limited by the genes that we have DNA probes for.

The safest form of germ-line alteration would be the removal of all cells containing the targeted gene. This would ensure that only the cells containing the good allele of a gene were present. This could occur through a targeted gene probe attached to a lethal piece of DNA. Once the probe reached the cells, it would affect only those cells that had the chosen gene, and would not affect the healthy cells. The converse approach would be to target cells which had the good gene, to protect them from a general elimination of germ cells. The germ cell stem cells are diploid, and could contain both a good and a bad allele, so this approach would not be effective.

Much current research has focused on the use of retroviral vectors as methods of targeted gene modification (Friedmann 1989). The germ cells could be altered if the DNA vector spread to many tissues of the body, either non-tissue specifically, or specifically. Since the adult may suffer from the disease, and the procedure assumes the gene is safe, a general body cell infection may be adequate.

Microinjection of Eggs and Zygotes

Microinjection of DNA into eggs is a technique with much animal experience, but the treated eggs still have a low viability. The most common procedure for gene transfer is microinjection of the DNA into one of the pronuclei of a recently developed zygote, which is transferred to a surrogate female for rearing. Generally about 1-4% of the injected mouse zygotes result in offspring with the gene integrated into the germline and capable of being inherited as a simple Mendelian dominant (Palmiter & Brinster 1986). It was reported in 1989 that sperm cells could take up DNA and produce transgenic mice, at a success rate of 5% (Lavitrano et al 1989). However at the time of writing this had not been repeated, so there are doubts about this technique (Beringer et al 1989). There are other techniques being developed such as the use of laser micropuncture of the cell membrane, electroporation, and biolistics (using high velocity tungsten microprojectiles containing DNA). These techniques are applicable to germ cells or the preembryo.

To use the procedure at the preembryo stage has the advantages that fertilisation has already occured, and a germ-line that exists is the subject of the work. There are techniques that increase the chances of fertilisation of a particular egg or sperm, such as injection of the sperm into the egg, but the preembryo is a desirable stage for any screening. It is after crossing over of the germ cell's DNA, which could produce further gene mutation. The embryos could be fertilised in vivo and flushed out for screening, or IVF could be used.

The genetic screening would also be a prerequisite to any therapeutic uses of germ-line manipulation. Only if the embryo requires gene correction would it be subject to that. Then the techniques of gene insertion could be used, or the fusion of the affected embryo with an embryonic stem cell line containing the normal gene. Using an embryonic stem cell line that had the necessary genes you could always guarantee the presence of the basic healthy genome.Embryonic stem cells

Experiments involving animals using germline gene therapy have been underway for a few years. In the initial demonstration of the use of the technique the human genes for growth hormone and a regulator were inserted into mice embryos and were expressed in the recipient mice doubling their body size. Germline transmission and expression of inserted genes has been possible in animals since 1982, however these crude methods involving multiple copies of genes are not applicable to humans. Only targeted gene replacement should be used. Also the technology still has a high failure rate in terms of the large losses of egg cells, and the failure to achieve any expression. There are major difficulties in the technique if applied to human embryos to avert the expression of a recessive mutant gene, especially in selecting the correct embryo for use. Also the response rate is low for embryos. With the way genetic information is transmitted in humans the genetic disease may not be expressed in the children, as they will only receive one of their pair of genes from the affected parent and would only be a carrier of the disease.

Experiments on animal models are a prerequisite to experiments on humans. One of the animal systems for gene therapy was that of Mason et al. (1986). Mice that were lacking the gene for the synthesis of gonadotrophic hormone releasing hormone were used in trials, in which DNA containing the correct gene was injected into fertilised eggs. The successfully treated animals were normal. Analogous experiments for other genes have been performed. It is unlikely that therapy originating from DNA injection into fertilised eggs will be considered as a means of restoring a deficient genotype in human (Charlton 1987) unless the genes can be targetted more specifically. It is also of limited usefulness, as it may be better just to avoid using gametes that have a genetic disease causing gene.

With microinjection, the transferred DNA inserts at a chromosome breakpoint. This is usually a single random site, and at this site there may be one to several hundred copies of the gene inserted. Only occasionally is more than one integration site observed. Homologous recombination is a desirable technique, as it involves the matching up of specific DNA sequences and the replacement or insertion (Figure 2-5) of a piece of DNA. The modification of genes by homologous recombination is commonly refered to as gene targeting (Bollag et al. 1989). It has been found that the gene targetting frequency in mammalian cells is independent of the number of target sequences present in the genome (Zheng & Wilson 1990). This means that the actual search for a specific DNA sequence is probably not the rate-limiting step in the process. In yeast cells however, the number of target sequences does affect the frequency of homologous recombination. The proportion of recombination events that are homologous, as opposed to non-homologous or random, is lower in mammalian cells than in yeast. The technique utilises natural cellular processes, and the experiments will help elucidate the natural processes of DNA repair.

Embryonic Stem Cell Lines

The way to get targeting is to include a homologous length of DNA in the insert compared to DNA at the desired chromosomal site. The frequency of homologous recombination occuring is between 1 in a 100 to 1000, and improving (Bialy 1990). To use this technology, it is easier to insert the gene into cells and screen the cells for successful gene targeting. Embryonic stem cells can be used, and only when one cell line with the desired insertion is obtained will it be inserted (Capecchi 1989). ES cells are preimplantation embryonic cells that can be maintained and genetically manipulated in culture, the selected cells are used to generate germline chimeric animals.

Gene targeting means that it is now potentially possible to generate mice of any desired genotype. ES cell lines have been used to create germ-line chimeras containing targeted gene alterations in the HPRT, ab 1, en -2, n-myc, B-2 microglobulin, igf -2 and int -1 genes (Capechhi 1990). They are very useful for the study of new methods of gene targetting. Methods to increase the ratio of homologous to nonhomologous recombination events are being developed (Bollag et al. 1989), Capecchi 1989). The frequency of successful hHomologous recombination must be increased if other methods are to be used.

It is possible that human chimeras could be made as a form of treatment for recessive diseases so that you could always guarantee the presence of the basic healthy genome by using a standard embryonic stem cell line, this might be more technically feasible than the alternatives. The capacity exists to make different human embryonic stem cell lines, it would just require making one without disease.


Health and Disease

We may aim for positive eugenics, but the judgements "healthy" and "unhealthy" are not clear if an extension is made from phenotypic symptoms to genetic (WCC 1982). What we need is to distinguish between eugenics, the selection of good genes and what we could call xialiogenics, or selection of healthy genes. We could split these new techniques into therapeutic and non-therapeutic (Fletcher 1983), with narrow boundaries (Leenan 1988). Non-therapeutic would include eugenic aims or enhancement (Anderson 1985). This distinction is more important than whether we are adding or subtracting genes. However, some argue that nonmedical reasons may also be ethical. If we accept it is good to correct a genetic disease, than we may also argue that it is good to improve our ability to resist cancer, it may also be good to increase our intelligence. The question is where do we draw the line?

The lack of a clear borderline between therapeutic and desired treatment is not just found in the question of using genetic techniques. It is also seen in the use of cosmetic plastic surgery, which can be used in extreme ways to change body appearance. Another example is the use of growth hormone treatment, where it should be given to dwarfs to become normal size, but can also be abused to make normal children grow to be very tall to aid their sporting potential. There are short children who are not deficient in growth hormone. The question is whether short statute is a disease. There is one medical argument for treating them on an association between shortness and psychological morbidity. But it is not sure whether growth hormone treatment will reduce this morbidity. Each individual will be different, and some other studies suggest that growth hormone does not relieve psychosocial problems in growth hormone-deficient children. There are serious doubts as to whether it will work. Also the treatment is expensive, currently costing US$20,000 per year for a 30kg child, who normally requires five years treatment. To treat those in the lower third of the height distribution in the United States would cost US$10 billion a year. The experimental and economic arguments are against this extension of using growth hormone (Lantos et al. 1989).

There are more medical therapies that will need to be considered, such as the alteration of genetic risk factors for disease, such as eliminating hypercholesterol levels in people so that they do not have a high risk for heart disease (Anderson 1985), or treating some genes that cause a disposition to certain cancers. If we spend large sums of money on increasing education and make children work very hard at school, to the point that they lack social interaction after school as in some countries, is it not better to aid their education by drugs or eventually by genes? The answer is probably that it is better not to expect such high standards. After spending time with some people of supposed high intelligence I would say that it is a goal that has got out of hand in many societies. It is also very dangerous to correlate the action of certain genes with very complex psychological attributes, such as behaviour. It takes attention away from the major social causes of such problems.

If we could insert a germline genetic alteration that would act as a vaccine against important diseases, such as Hepatitis, Malaria or AIDS, would not these be justified. Even more so if a genetic vaccine for the diseases of the developing nations could be developed, and effectively delivered. Given that the economic inequalities may not change, it may be the only way to reach the majority of the world's population. It would also have strong reasons for universal application, like the eradication of smallpox. People must think very seriously when they tend to sweep any notion of germline genetic manipulation under the carpet. We need to think of using any technology that may provide benefits, only after doing so, will we be in a place to ethically reject or accept it. If such a scheme is permitted, it should be distributed justly, and fairly to all.

Carriers of Harmful Alleles May Be "Healthier"

The concept we need is selection of health, though in a narrower sense than the World Health Organisations criteria of health, referring rather to the absence of disease causing genes. While a person may look healthy, we all carry up to 10 recessive genes, which if matched up to another allele to form the homozygous condition would produce a lethal disease. A further problem is the difference in the phenotypic states between those people of heterozygous and homozygous (two copies) state for certain alleles, e.g. in sickle cell anemia the homozygous trait is lethal, but people in the heterozygous state are more resistant to malaria. The result is a much higher level of this allele in people of central Africa where it has proved advantageous to carry this allele as it confered resistance to malaria, even though more people die when born with the homozygous state. The percentage of sufferers of sickle cell anemia in Central Africa compared to North America are 2.5-8%/0.3-1.3% , and the percentage of carriers of the allele are 30+%/10% respectively.

Sickle cell disease is a classic case but other examples have been found. The heterozygote form of the recessive gene for congenital adrenal hyperplasia appears to protect Yupik Eskimos against infection with Hemophilus influence B. The Tay-Sach's disease-causing allele appears to confer advantages against tuberculosis, and several similar lipid-storage diseases may also have advantages if suffering from tuberculosis. A different type of compensation is seen in idiopathic hemochromatosis that is found at a heterozygote frequency of 10% of the population of Europe and America. The abnormality results in increased iron absorption, which is an advantage for women, but not for men, as it can be fatal. The high incidence of insulin-dependent diabetes seen within a few decades after the people carrying the disorder (Yemenite Jews, Pima Indians and Micronesians) shifted to a Western diet after previously living in conditions of food scarcity is another point. The disorder is actually an advantage if under starvation conditions, but a disorder with a different diet (Rotter & Diamond 1987)

Another disorder is glucose-6-phosphate dehydrogenase deficiency which increases resistance to malaria, and is harmful only if eating fava beans and when taking certain drugs. These examples must make us look carefully at categorizing disease. It is difficult to draw the line sometimes, so that an arbitrary barrier may be needed. There are strong arguments on a secular level, including the discussed uncertainties of manipulation, to make large scale eugenics ethically undesirable. But we may still feel that if it is possible, it is better to start helping people come into the world healthy if we can do so at some point in the future.

Spontaneous Mutations Will Continue to Occur

The total elimination of all disease-causing alleles is an unrealistic goal, and is unobtainable. It is not possible to erradicate genetic disease completely as many people are carriers for genetic disease and are not aware of it, and many occur spontaneously as new gene mutations in the parents' gamete producing cells. One third of hemophilia and two thirds of muscular dystrophy are the result of new mutations. Studies with gene-specific probes have demonstrated that the mutations resulting in a particular phenotype are highly heterogeneous as a group (Davies & Robson 1987). So even in diseases where the natural mutation rate is very low it is sufficient to maintain a rare stock of these altered genes. The amount of these natural mutations increases as we are exposed to more environmental hazards from pollution.

Elimination of disease-carrying alleles is not necessary for the health of the population if genetic screening and therapy is available. It is also important to recognise that germ-line engineering will still not solve the problems of genetic disease. Every generation will have this problem, which may need the use of embryo screening, to detect those individuals conceived with a new mutation, and the future development of medical therapies.

Human germline gene therapy is not currently legal in the USA (RAC 1986) and some other countries, but it is viewed as one day becoming appropriate, in some cases. There will always be a need for somatic cell gene therapy anyway, as it can be performed on individuals at any stage of development, while germline gene therapy needs to be performed on either the gametes at an early stage or on the very early embryo. A certain type of somatic cell therapy can be envisaged that will modify all cells of the body, including gamete-producing cells, so that the next generation could be treated, but the large number of spontaneously occuring cases could not be.


Ethics of Germline Genetic Engineering

We Already Change the Genes of Children

Although we may feel very uncomfortable at the idea of altering genes, we should be clear on one thing, we all do it. We decide to bred, or not to, and how many children to have, and who to get married to. We do not like disease, so we try to treat it, and most parents would replace a deleterious gene in their children to be if that would save them from illness. There is no medical reason not to replace disease-causing genes with normal genes to avoid disease in future generations. It is clearly different to the type of eugenics that people object to, it is rather xialogenic.

Some argue that we should not remove a gene from the population because it may later prove to be useful. If we take the case of sickle cell anemia as above, if people are carriers of one healthy and one diseased allele than there is no effect on normal life, unless you are present in malarial areas, but if two carriers marry than they have a one in four chance of having a child that will die from the condition. The alternatives for those parents are several, they can have premarital screening and alter their marriage plans, they can have genetic screening of the embryo and selective abortion, or in the future have gene therapy of the somatic cell type on any affected baby, or have germline gene therapy. Once the technique of germline gene therapy is satisfactory then it may be the best alternative to preserve their choice of marriage partner. The choice of a marriage partner should be based on personality compatibility, and love for each other, rather than checking through a list of suitable gene donors for procreation. The harms from not eliminating the disease carrying gene are greater than the possibility that the trait may avoid malarial infection, at least in countries where malaria is no problem. In fact current antibiotics and sanitation have been much more effective in protecting the same populations who have sickle cell anemia, from malaria. If we are worried about the loss in genetic variety, then we should not be, as there are multiple forms of healthy genes existing anyway, what is called polymorphism. There are several possible healthy alleles for many genes, yet all are functional, so that could preserve genetic variety to maintain the diversity of genes that might be needed for future diseases (OTA 1987a). There are at least 46 distinct alleles of the gene phenylalanine hydroxylase (a mutated allele is responsible for the disease PKU). We do not violate any "rights" of future offspring by removing harmful genes, rather they will be grateful that they do not suffer from the disease, the same as if they are treated by medicine when alive. There will be plenty of nongenetic diseases to suffer from even if we can remove many genetic diseases.

The objection that we would be Playing God reminds us that we do not know enough to change any genes except those that cause disease, and should not go beyond that. We need to examine the whole of modern medicine, along with the reason why many diseased people live. It is because of much life-sustaining technology, which is a half way solution to the problem which in certain situations can appear to be worse than non-treatment as it only provides longer life without any cure or treatment. We are already intervening in nature, but not well enough. As a precaution, we could change only one allele when performing germline changes, so that genetic screening could be used for the next generation if something went wrong with the gene, so that the rest of the genome could be passed on. Though if we possess the techniques for gene insertion we would also be able to alter the gene in subsequent generations.

Some think that characteristics such as personality and intelligence are probably outside the potential of gene therapy control, and there are other simpler measures which any insane individual dictator could use (and have), such as drugs or sociological pressures, to control society (Cherfas 1982). Some scientists believe that we will only be able to change human phenotype in small ways by genetic manipulation, less than we can by social and environmental influences (Rose 1984). Fear of genetic manipulation owes a great deal to the excesses and associations of eugenics (Kevles 1985, Nossal 1985, Ledley 1987). A principle of human life held by many to be fundamental is that there is a right for men and women, with regard to their fellow human beings, to have the choice of their own partner in marriage and to decide whether they should reproduce, and this can never be overruled by considerations of their class or their religious outlooks, or on economic or biological grounds. The government may offer incentives or discentives, but those policies are for society as a whole and should not be in breach of human rights. There are already genetic screening programmes used by some employers and insurance companies as we discussed in chapter 13. This does not imply that people have a right to use any technological means to alter the genetic characteristics of themselves or future children.

We may ask, is it worthwhile to use these techniques? Why should we try to fix the germ-lines of a few, why not just encourage the use of donor germ cells and avoid the use of defective germ cells altogether. This may work on a small scale, but if we consider the fact that every individual carries a dozen or more alleles that cause genetic disease, than we will still be using germ cells with potential for disease. A carrier of a recessive allele for a genetic disease is the normal situation of every individual on this planet, something that should be a basic piece of information for anybody undergoing genetic counseling. It is not the objective of germ-line engineering to change this, rather the realistic goal is to have healthy people, as stated above. It is an impossible goal to fix all the potentially disease causing genes and those who start the "game" should know the limits.

The idea of genetic health is implied, but it turns out to be very difficult to define. It is possible for an individual to have many harmful recessive alleles, but to be phenotypically healthy. In fact we are all estimated to have perhaps ten recessive alleles that would be lethal in the homozygous state. To make it more complicated in the heterozygous state there can be advantages to possessing one of these bad alleles. The health of any complex organism is the result of many interactions between genes and the environment, and health is a concept that should apply to the system as a whole, whether it be cell, tissue or being, but not to the genes. One of the goals of eugenics is to improve the genetic health of the population, but this is impossible to specify. However, there is still a question of the individual's duties to society in their reproductive choice, which is a fundamental issue. Rather medicine has to consider improving the health of individuals which will include some genetic therapy when possible.

Consumer Children

This is a more realistic objection to the new technologies, and we have seen the emergence of commercial surrogacy as a prime example of this. It could also be said of private IVF clinics which are making a profit on providing this medical service. It is a very sensitive area, and is related to the feeling against slavery of human beings, and the growing influence in society that says that we can buy anything if we have the money. There is also the issue of chosing the desired characters in a child, that will be possible in increasingly more precise ways. This is a more important issue, and has a new element. It is one thing to chose the spouse because of the characters that they have which one hopes will be passed to the children, and to be a parent to our children, but another to actually select the child. There are long traditions in different cultures that involve careful scrutiny of the relatives of a marriage candidate in the selection process, so that relatives of epileptics or people of genetic disability may be selected against, particularly seen with Jews or in Japan. These may have been developed to protect these ancient societies eugenically, but are not longer justified because of modern medicine and genetic screening.

If genetic engineering and genetic selection allows parents to pick and chose their children, then it encourages the replacement of personal and permanent family relationships with instrumental and impermanent relationships (Brody 1981). The social consequences are very important, but may be hard to determine (Weatheral & Shelby 1989). The relationships in a family are unique in that they are personal, permanent and are not chosen by the parties. Divorce can undermine this, which is also a bad influence. We are always in the relationship just because of being a member, we do not have to prove ourselves as we do in other relationships. Family relationships are mutually supportive. Instrumental relationships are the normal outside of the family, we value other people for what they can do for us and their roles. There is an implied threat that if parents chose a certain type of child, then if the children do not perform they will be rejected. This tendency is a real danger in countries where prenatal screening is being used for trivial conditions, such as sex selection. Even if the character chosen is a primary good such as intelligence, it is good only in certain careers to have exceptional intelligence. The parents should be bringing up the child to develop their individual autonomy, and should not impose parental expectations on the child.

Behind the idea of defectiveness is the image of a perfect human being, but we should be clear that we can not be. There is a growing idea that we can improve the human species, and that we can improve on nature. Attached to this is the idea that we can alter human beings morally by altering them biologically. The idea is that we need to increase human quality (Fletcher 1988).

Slaves to the New Technology

We have changed society dramatically in the twentieth century by the pasteurization of milk, sanitary food, antiseptic hospital conditions, compulsory immunisation programs and antibiotics. Though these are still to fully reach many people in 1990. While there are still major infectious diseases, for instance 1500 million still are exposed to malaria, in many parts of the world genetic diseases have been highlighted by the control of infectious disease. There is now the philosophy that since we have got rid of some infectious diseases, such as smallpox, we should work to eliminate genetic disease. Children may be produced in a quality control environment, with special characteristics, or else the fetus may be eliminated before it grows into a child. We need to concentrate not on a continued push of technology for itself, but rather for the benefit of individual patients.

While rationality is a high human virtue, it is a contentious matter as to whether it is the highest human virtue, there are many others that are often considered higher, such as love, charity, joy, ability to live peacefully, variety of people, and many culturally dependent virtues. If a new technology becomes available it may not be the most rational course to use it, and even if we do embark there are often hidden dangers. Related to this is the general theme of science as a means to Utopia. There is a major feeling that the progress of society can occur together with scientific advance. However, there will be points where scientific progress will not improve society, and there are already many who think that we have got worse in this technical age. Genetics is far from being unique as an element of social change, there are many others that appear permanent and have ill effects such as the centralisation of commercial shops with the disappearance of local shops, the growing addiction to watching television, and the dangers of the computer revolution.

While the ability to pick and chose our children can have a damaging affect on our attitude to children, it can also have a damaging affect on the autonomy of reproductive choice of parents. While there may be a right to free choice of marriage partner, and this should never be compromised in a society that respects the autonomy of individuals, there is not an unconditional right to bring up children. If parents miss treat the children and abuse them, they will be taken away, for the best interests of the child. However, what about the right to bear children with genetic disease. This is a very contentious issue but one that is arising. Earlier in this century it arose with the compulsory sterilisation programs of USA or some of Europe. Britain did not authorise such a sterilisation program, but did prevent marriages, which could be argued to be more of a violation of rights. However, the extent of the sterilisation programs and the racial ideas which were behind much of them is a much more vivid memory. The rejection of these programs was due to two things, one was the lack of scientific evidence for the disease conditions, and the other was growing awareness of the rights of individuals and the excesses of the Nazis. However, today we have growing scientific basis for some of the genetic links with disease, and so the only barrier to a return to compulsory eugenics is a recognition of the autonomy of individuals.

The mechanism of selection can be voluntary also, by subtle propaganda and by medical insurance schemes which indirectly enforce cooperation. There is certainly a responsibility of good parenthood, but like other issues it is a moving line. There is a long history of parental responsibility in passing on education, some material wealth, and providing care for children born. There will also be responsibility to ensure the health of the fetus to some degree. This however can become restrictive on the adult, which affects the pregnant women, and the medical interventions that are recommended. There is already the knowledge of behaviour that is detrimental to fetal health such as smoking, overdrinking, or many drugs (both legal and illegal), yet enforcing strict behavioural regimes can intrude on a women's autonomy. Of course mothers want there children to be healthy but there is a limit. We need to question what is the goal of society. For several decades after World War II there was a feeling that science and technology could provide everything, and they should be promoted. Many saw that only science based technology could change our society for the better. However, during the last two decades there has been a growing feeling that technology has actually led to many problems as well as benefits. There has been a growing and strong anti-technology feeling (not so much a anti-science feeling) (Cavalieri 1985). Scientists assume that science is naturally good for society, but this is not an unconditional assumption.

We should remember the parallel between biotechnology and computers also, both are thought to give rise to major changes in society, and they are both having some impact. In the early days of the computer revolution the computer was going to change radically every aspect of human life if some people were listened too. But today we do not hear so much about this, though I doubt it is because it has lost its potential power for change, but rather that society has accepted the changes so far, which for most people have been for the better. However, with biotechnology we are dealing with the complexity of life itself, which may have greater potential. It has also begun, and society is accepting it and society will continue to change. There is a need for more consideration of the way in which society changes and whether this is for the better or not.

Protecting Future Generations

We are often uncertain of the precise outcome of interventions in nature or medicine. Fortunately nowdays most are ready to admit that uncertainty, which while being the norm in medicine, has taken major ecological disasters to convince people in industry or agriculture. We will never be certain to have complete control over the effects of introducing new gene sequences, and with many cases much further experimentation is required before we will be able to ethically allow full scale use of them. Ignorance of the consequences means caution in using new techniques, and this is an approach seen in the regulations governing the use of human gene therapy.

There have been regulations and legislation brought in which oppose the use of germ-line manipulation. Some of the restrictions apply only to procedures other than to cure a hereditary disorder, but others are more general. The British Human Fertilisation and Embryology Bill would outlaw germ-line gene therapy on embryos. The European Council has passed a recommendation stating that every new individual has the right to a genetic constitution that has not been interfered with. In 1988 the European Medical Research Councils issued a joint statement stating that "germ-line gene therapy should not be contemplated", neither should enhancement genetic engineering (EMRC 1988). In the USA germline gene therapy is not considered yet, but may be so at a later stage. The National Health and Medical Council of Australia Report stated that germ cell gene therapy is ethically unacceptable. In the state of Victoria, Australia, it would be illegal. The reaction against germ-line manipulation has been widespread. The International Organisation of Scientists for Social Responsibility has proposed that the United Nations add an article to the Human Rights articles, saying that a human genetic inheritance should not be modified, except by using somatic cell gene therapy. However, while the technology is not sufficiently safe to predict outcome gene therapy should not be used, it does not need to be legislated against before proper discussion has occured. If society can allow somatic cell alterations such as cosmetic surgery, or independent schooling, there may be a case for genetic freedom. On the otherhand, legislation against germline manipulation can be useful as a barrier to hasty use of germline manipulation, as extensive discussion would be required to reverse the legislation and general societal approval would be needed. There is a case for both approaches.

Germline gene therapy involves all future generations. Parents do make decisions concerning their child's health and we can assume that future children do not want to be ill (Leenan 1988). This assumption is already used in some compulsory genetic screening for PKU and other diseases in newborns, and is consistent with good parenthood. However, these decisions are not usually so far reaching. The concern for long range consequences is an important part of contemporary ethics (Jonas 1976). We have a duty to consider the second-order remote consequences of any course of action, when debating the ethics of that action. Ethics was generally restricted to considerations of relatively short term consequences, within the immediate community. Modern technology means that man has become an object of his own power, not with external effects, but internally.

Our decisions can have far-reaching consequences as to the identity of the child, but it is another question as to whether this is important if the same number of children is considered. For instance, if "I" was conceived from a different egg and sperm "I" would be different, and someone else would be in my family who may not be writing this book. But, if I never existed and my parents had another child, would the family situation be very different? They would still have a child, and that person would be of equal value to myself. I could not accuse my parents of having me, as I would never had existed. These types of choices have been discussed by philosophers, and are important for this type of longterm public planning, including the use of genetic engineering on future generations, and genetic screening and selective abortion.

There are different ways in which a given individual might be different from what they are, but the point at which they become a different individual is often viewed as when they were formed from the union of different gametes. In view of the earlier discussion about the status of the human embryo in chapter 5, in particular on the origins of individual life (Ford 1988), rather than concentrating on the fertilised egg or zygote we should focus on the earliest item from which the individual is uniquely developed (Williams 1990). The idea that an individual is principally distinguished by the joining of two unique zygotes, above all other differences is called the zygotic principle (Parfit 1984). The zygotic principle represents the view that different individual fetuses will be different people, though it does not maintain that a human person is formed at conception, or the formation of the primitive streak, or viability, or some particular point in development (Williams 1990).

If a parent suffers from a serious genetic disease then the child can not be held responsible for it. They may blame parents, or others, such as chemical companies who released poisons in the environment, but we cannot attribute blame to those who suffer from the disease. If we live in a just society we will look after their special needs. However, if the person decides to conceive a child knowing that they might suffer from that disease, which could be detected by prenatal diagnosis to confirm the condition, if they know that fetus will be afflicted, they do have some blame for the child's disease. If they use prenatal diagnosis and find that the first fetus is suffering, and abort it, and have a second child which is healthy they will have good reasons for waiting to conceive a fetus that is free of the disease (Hanser 1990). It is not possible for some individual to say that if their parents had waited until later that they would not be handicapped, as there would be a different individual. In the case of genetic screening, one individual cannot express the concern that 'even if it would not have been them but that the other person would have had a better life', because they do not even exist. However it is philosophically possible for them to say that it may have been better for them not to exist (Williams 1990). However, it is a very different step for this concept to be accepted legally, as in the case of "wrongful life", and it is socially undesirable to do so. If they have the chance to use genetic engineering to ensure that the fetus is normal and they do not, than the parents might be held even more to blame than in the case involving abortion. If the question is one of the parents using genetic engineering to treat the same individual then that individual can say that they would have had a better life as themselves if their parents had used it. The same blame could be attributed to a government that withholds such a technique from being available to the public if it has reasonable resources to implement such therapy. The argument is similar to that used to justify other medical techniques, and when safe genetic engineering is available and a better alternative to other therapies for the individual, than there will be pressure to make it available.

Somatic cell gene therapy will lead to germline gene therapy. With germline gene therapy we may all agree on the treatment for some specific diseases, but there will be a "slippery slope" towards research to modify other less clearly undesirable human traits or even toward modification of human characteristics for malevolent purposes. There are limitations as we may misuse the possibilities offered us as we often have, this is however not an argument against their use, but a reminder of our limitations. We may have to live with the disadvantages to benefit from the techniques. But a danger exists if we do not use germline gene therapy but only somatic cell therapy. Somatic cell gene therapy could not prevent perpetuation of the disease, so the future generation would need to be treated as their parents needed.

Germline gene therapy used for eugenic purposes is in the category referred to by Lewis (1947), a long-term exercise of power which means the power of earlier generations will be over the later ones. The last men, will not be heirs of the power but will be of all men most subject to the great planners and conditioners of the past. An "advance" such as this leaves men weaker, as well as stronger. Technology seeks to do or to act rather than to merely understand genetics, and hence is associated with power. The power will be held by a certain portion of the population. This power has long range consequences as it is not confined to the present people, but extends to future generations. Although each generation does make decisions that affect the next, the type of affect that they have had in the past have been restricted to the type of political system, religion, cultural value system. During the last century we've seen more dramatic changes, such as brought about by the industrial and scientific revolutions, and global changes to the environment such as the Greenhouse Affect or depletion of the ozone layer. However, genetic manipulation is a more direct change then these, as it alters ourselves directly. The category of decision may not be completely new, but the consequences of the decision to human beings are certainly greater. The problem of policy becomes one to ensure that the powers which are accruing to some individuals are not abused.

Shirmacher (1987) argues that with the use of genetic technology man has become homo generator. We no longer have to settle for what we are given, instead we can alter the "fundamental building blocks" of life. People may denounce this new role, a reason for the great concern about genetic engineering, but he sees it as consistent with our role in evolution.

It has been claimed that genetic engineering is like nuclear science, as both confer a power on humans for which they are psychologically and morally unprepared (Cavalieri 1985). Certainly biologists claim that they can outdo evolution, and use genetic engineering widely but the question is whether we are ready for this new power. In the 1940's we learnt how to use nuclear fission, and physicists initially motivated by the aim of developing a weapon to use on fascist Germany, became so wound up in their work that they did not slow down when they knew it would not be needed. After our experience with atomic power we should face the biological revolution with our eye's open, the question is whether we do.

Another question is in whose hands will the power be, with the scientists or under commercial control. While scientists might be able to retain control initially, it is very likely that like all developments involving much commercial interests, the commercial interest will dominate. Much of the research in these areas is paid for by commercial companies, even human gene therapy has commercial backers. Genetic screening tests are being commercially sold, medicine is very big business, as we already know from the huge number of duplicate drugs and the pharmaceutical companies.

In our commercially minded world it is not surprising that many companies have invested much in biotechnology and they are beginning to get some of the benefits. Many things have been patented, many processes, including patents for animals. There are some technologies that have not been patented, such as much of those involved with in vitro fertilisation, but other areas are. There are arguments to say that this creates much more research money, as it may, but there are also growing dangers of the control of valuable drugs and technology by major countries. The resources of this are genes, and it is interesting that the major gene banks are controlled by the wealthy countries. As we cause the extinction of many species we lose many potentially valuable genes, so germ storage banks have been developed. The world's genetic pool is under control of these places, and a type of gene imperialism (Rifkin 1985) could develop. We must be careful that this technology is shared out, as the new agricultural species are most needed in the third world. This problem is not unique to genetics though, and is appropriate to many other areas under commercial control.

Because the changes are not easily reversible, and potentially irreversible, and involve human nature, there are very strong reasons to say that we should not impose the ideals of the genetic engineer upon the future generations. We can see how quickly that human ideals change, over ideas such as beauty, good personality, intelligence level and talents, between cultures and generations. We have no right to set our current ideal of favoured traits for future generations. The great variety of human beings is one of the greatest virtues of the human race, more than intelligence or sporting ability. The variety of people with different talents is essential for human society. We could object to any adjusting of human virtues by imposing fixed genetic blueprints on human beings. We still have power to change the future, through education, and this process will continue. Social ideas should be allowed to develop further without interfering in the process. Ethical arguments join public policy arguments in opposing enhancement genetic engineering.

With all this said, there is still a case for attempting to cure disease on a large scale. It is not unethical to extend symptomatic treatment for disease, to treatment of genes to prevent the disease being passed on. In fact every human being has some recessive lethal alleles, which if paired would cause death, and/or genetic disease. It is practically impossible to erradicate this from the human race, as every new individual produces new mutations (Ledley 1987).

Imagine the situation when we know that some alleles of a gene cause susceptibility to criminal behaviour. We have jails that are full of hardened criminals, some of whom have this gene. Should we change it? Should the sentence be moved from life imprisonment to genetic correction and rehabilitation. The fairest may be to give the option to the criminal to decide, if such a therapy worked. We must be careful in the degree to which we put excuses for behaviour in the genes that people have, but it may well be a major part, together with childhood experiences and environmental reinforcement.

It does not seem ethical under any system of morality to genetically engineer peoples' personalities to the "ideal" image of another person. While it is relatively easy to call a disease a disease, many subtle variations in personality are generally believed to be virtues of humanity given by God. There are limits to the employment of techniques, not necessarily taught by compassion, but by understanding what God has made. As O'Donovan (1984) has said, every technique may need its sabbath rest, a point beyond which we don't interfere but appreciate God's creation. But the possibility could only be envisaged if genetic engineering became widespread and used for treatment of more things than genetic disease. This is something we must always guard ourselves from, but we should not let it limit our therapeutic use of the techniques now.

Positive eugenics through germline gene therapy might seem more acceptable than negative eugenics, or selective abortion used in many cases now, but while we are unsure of the positive outcomes from therapy, selective abortion may be preferable. It may be that our application of life-saving technology is premature, that we should save lives when there is some hope of the life being restored. It can be argued that it is playing God too much to intervene in cases when we can not restore health. Gene therapy is more acceptable than selective abortion if we consider a fetus of any age to to possess the rights of a human. However, that is not the view expressed in this book of an embryo in the first two months after conception. It could also be argued that the risk to the individual of possible bad consequences after genetic manipulation, especially as the technique is first being developed, is unethical and it is in the best interests of the potential person not to cause harm. The cost of gene therapy is also more important, which is important when rationing health care fairly. If prenatal screening can be performed at 6-8 weeks, which is possible, then it may be ethically preferable. If done later than that time, gene therapy would be more consistent with the view of the human embryo expressed in this book. The best approach depends on the weighing of the relative technical reliability of each procedure, which will change with time.

We assume that future children do not want to be ill, which is justified. This is the assumption used in compulsory genetic screening for diseases such as PKU in newborns. It could even be said to be more consistent to want children not to suffer from disease, and to use reasonable and safe methods to ensure this, than not to use such medicine. However, it could be argued that to interfere unnecessarily with every conception to screen it during the first week to decide whether to use germline gene therapy would be quite unethical, as well as being impractical. If screening embryos from parents who are both carriers of a recessive disease like cystic fibrosis, then one in four embryos would be affected, in view of the other embryos that could be made unaffected, then this is the limit of the interference needed to correct the disease. With the resulting possibilities for "enhancement" of human capabilities by genetic means or eugenics programs encouraged or even enforced by governments. What these possibilities do suggest, however, is that strong controlling committees must be established to control the use of these new techniques to monitor where they are developing. This may help to ensure proper guidance of the use of gene therapy so that it may be more beneficial, and to prevent any misuse through premature or undesirable application. They should also help to generate awareness of the way in which genetic engineering practises may alter social values and important interpersonal relationships. Currently there is little consensus on the moral approach we should use in dealing with germline genetic manipulation (Anderson 1985). There needs to be guidelines and legislation in areas relating to what we can do now, to protect society.

Uncertainties in the techniques may allow for unforseen disastrous consequences, and we will remain largely ignorant about the longterm consequences of altering the basic genetic makeup of our race - but correcting disease only needs the repairing of mutations that have occured, which will not lead to any new problems. There will always be a wide genetic diversity in the many other traits we possess. Suffering can not be erradicated by changing our genes, and this should not be the ultimate aim of medical therapy.


Cloning

After the development of the technique of assexual reproduction of clonal frogs in the mid-1960's there was a period of much debate considering the possibility and ethics of cloning humans. There was increased publicity associated with the now assumed fraud of David Rorvik's book "In His Image" (1978), further progressing the debate. The topic of cloning was also dominant in Aldous Huxley's "Brave New World". Of the many types of ideas on the science dominated future of man, the most sensitive area is the things that affect the inner constitution of humans. However, since then most discussions of cloning pass it off as unlikely to occur in the near future, or as improbable. Some recent developments have led to cloned mammals which makes the possibilities for cloned humans much more immediate.

Techniques for "Cloning"

There is an early report of nuclear replacement in mature human ova resulting in cleavage of the ova to the two cell stage (Shettles 1979), but this work has not led to any further published success, as it is often found that a dividing preembryo made in this sort of way will cease to divide differentially and either die or start dividing somatically. There is the reported case of a possible two cell parthenogenetic human embryo that was aspirated at oocyte retrival for IVF (Padilla et al. 1987). It is not thought that any fetuses have developed from such an embryo, and it appears that for proper development of mammalian embryos genes from both parents are needed, as genes are differentially used from paternal or maternal chromosomes.

The use of IVF and embryo transfer has been progressing, and has become well established for human reproduction. Even when Edwards and Steptoe, and others, were developing these techniques, the potential for further applications to cloning was noted by some scientists (Watson 1971). It is certainly possible to split human embryos to provide a cell or two for DNA analysis for preimplantation genetic screening as discussed in chapter 13.

It is also possible to split a human embryo to produce twins, depending on how far they see regulations permit this. From experience with animal studies there would seem little to fear from ill effects on the babies, and identical twins are not unnatural. Blastomeres of early cleavage-stage embryos of cattle, horses, pigs, sheep and mice have resulted in normal development from as little as a quarter of the normal complement of cells. There have been live births of 2-4 clones. Development and the ease of manipulation may be species dependent.

There are human teratocarcinoma derived embryo stem cell lines which could be used in transferring genetic information to human embryos. Chimeras can be produced, and a standard embryonic stem cell line used in many embryos to make partial clones. This is technically possible now. We do not need to speculate on the time such technology will be available any more, it already exists, the only question is when it will be safe to begin, and if it is ethical.

Ethical Concerns

There have been quite a few objections to human cloning. The major one would appear to be that we must be sure that any clonal human when born does not have some defect the result of the cloning process, such as the rules used when we think of gene therapy. The rules used for prohibiting germline gene therapy could be applied to attempts at human cloning, as you could say splitting of an embryo is a genetic manipulation. The problem might be, that preimplantation diagnosis of an embryo by taking one cell away from an 8-cell embryo, might be a justifiable technique, as from the experience from animals there seems little risk to the offspring. Though also animal embryo splitting experiments have not reportedly produced mutant live births (the embryos may fail to develop in utero if damaged), but better records need to be kept to be sure of this (Monk et al. 1988).

Some object to cloning on the grounds that it is against natural law or is "playing God", as for genetic manipulation in general. The objection is valid to some degree, as discussed in earlier chapters, and more so when we consider human beings. We do use technology in many ways in medicine, and the objection can be overcome if we could satisfy more important questions, the primary one being does it benefit the individuals to be born. However, to the twins made by embryo splitting this objection would not be relevant, as identical twins occur naturally.

There is the objection that it would reduce the genetic diversity of a species if it was made from many clones, but this would only apply if we were making a significant proportion of the breeding population asexually. We should always try to maintain diverse organisms, as they tend to be better able, as a population, to survive major diseases or environmental changes.

There have been ideas of human cloning proposed by some scientists, or extreme philosophers, as being desirable. There have been propositions of the advantages of human cloning even advanced in the Soviet Union, which since the 1930's was hostile to such eugenic ideas. There are not many supporters, but a few (Graham 1987). There is still much reserve concerning any applications of human genetics, and there is still a strong nature/nurture debate, and fears that it would strengthen the elite in society.

Other objections to human cloning such as the psychological problems (Ramsey 1970, Glover 1984, LaBar 1984), it being a misapplication of health care resources, it will change our attitudes to children, and to the way we reproduce (Cherfas 1985), could also be applied to other birth technologies. It has been suggested that it may lessen the respect for individual person's (Chadwick 1982), because of the feeling that they could easily be replaced. These problems are hard to

assess, but what appears to be a crucial question is the number of clones. If the number is small, many of these problems would not exist. Having the identical genotype certainly does not result in the same people, as environmental influence appears to be a major controller of behaviour. At least it is sufficient to ensure differences between genetic clones. We do not call identical twins clones, even though genetically they are. They are obviously very different in many cases.

There is still concern about deliberately creating identical humans, and the Council of Europe has recommended that creation of identical twins after IVF be forbidden as discussed in chapter 5. However, if we can satisfy the criteria that the individual will not be damaged because of the technique, it would not be a major step to use embryo splitting after IVF to implant twin embryos. This might be especially applicable to patients who use IVF and preimplantation diagnosis for genetic disease, so that the preembryo found to be free of the defect could be split to improve the chances of embryo transfer giving rise to a successful pregnancy. Ten years ago this was not thought to become preferable to AID or egg donation (Eisenberg 1976), but it may be.

In the laws of most of the countries that permit human embryo research are clauses to prevent research into cloning or parthenogenetic development. Several specifically state that the genotype should not be interfered with. Recommendation 934 of the Council of Europe (1982) covered the application of human genetics and "out of respect for the genetic heritage of mankind" said the genotype should not be interfered with in individuals, "save for clearly and scientifically demonstrated preventive or therapeutic purposes". Recommendation 1100 of the Council of Europe (1989), in accordance with the earlier recommendations, 934 and 1046, permits investigations of viable embryos in vitro only "for applied purposes of a diagnostic nature or for preventive or therapeutic purposes", and "if their non-pathological genetic heritage is not interfered with". Thus, it does leave the opportunity for preimplantation diagnosis, and the possibility for future genetic engineering that cures disease. Genetic research is permitted subject to approval for diagnostic purposes, and also for pre-industrial research if the substances can not be produced in any other way. The recommendations do forbid therapy on the human germinal line, however, they do support somatic cell gene therapy and the insertion of organoids expressing therapeutic genes.

In clinical use of IVF there is the case for some embryo splitting, for diagnosis, and implantation of twins. The rules for embryo experimentation would apply to any embryo, made by any means, by splitting or by some potential embryonic stem cell line. The original goal forseen for cloning was to make copies of some adult, this is not the main pursuit of the cloning we have. The use of cloning to bring in designed genetic change has been accomplished in a limited way using embryonic stem cell lines to make new strains of mice, but it would not seem to be an ethical pursuit if applied to human beings, even if the motivation is honourable. Skills in human embryo manipulation are improving, so in the future it may reach the stage where it presents negligible physical risk to an individual. Therefore, the case has to examined for what problems this will pose to family attitudes, and society's attitudes to the to the child.

The work with ES cells, if conducted within the time and developmental limits for human embryo experimentation, is justified only if we are prepared to justify some human embryo experiments for their scientific or medical benefit. This class of experiments could also be reviewed by the regulatory authorities, in light of the fact that genetic manipulation can yield much scientific information, and the major interest in the roles of genes in development. We could imagine some longterm extrapolation to use for corrective germline gene therapy, however these experiments it could only be justifiable by use of what seems now to be unethical trials, which the first subjects would be. Maybe the work could be progressed on animals to a stage where exact predictability could be reached, in which case there might be some grounds. As discussed, the advantage of using ES cell lines and homologous recombination over the use of retroviruses is the stability of the incorporated genes. If the genes can be manipulated in their natural chromosomal environments, whereas the use of conventional methods for introducing DNA sequences into the germ line allows little control over the chromosomal site of integration and the number of integrated copies.


Human Genome Projects

By mid 1990 we possessed the gene sequences of over 5,000 human genes, and the location of 1,700 genes to areas of specific chromosomes (McKusick 1990). However, the total number of human genes is thought to be between 50,000 and 100,000. The genome projects aim to sequence all this DNA. Moreover this compromises only 5-10% of the total DNA in the human genome. The rest of the DNA is thought to be nonfunctional. These figures start to give the idea of the size of the projects to obtain a complete sequence of the human genome (a total of about 2.8 billion linear bases on 23 chromosomes).

The Scientific Approach

The scientific methodology for sequencing DNA is routine, but the cost of US$3-5 for each nucleotide must be reduced by a tenth before the major sequencing effort. This should occur as automatic DNA sequencing methods are improved. The first complete DNA sequences to be determined were of smaller DNA viruses, such as simian virus 40, which contains about 5,000 base pairs, in 1977. By 1982 the tenfold larger sequence of bacteriophage lambda was known, and by 1984 the herpesvirus Epstein-Barr virus sequence of over 100,000 base pairs was known. The total length of human gene sequences that are known today is about 40 million base pairs (Watson 1990). Within the this decade the sequence of the bacterium Escherichia coli should be determined, already 800,000 base pairs of its 4,800,000 base pair genome has been determined. The human genome is still 1,000 times greater than this.

Because over 90% of the DNA is thought to be nonfunctional, some critics have said it is a waste of resources to sequence all the DNA. Critics can call the noncoding information garbage, but as has been said, it is not junk (CIBA 1990), and a better word is to call it non-coding. There are very important functions of noncoding DNA, such as the regions of repeated sequence that are found at the sites of chromosomal organisation, such as telomeres and centromeres. These sites are necessary for organisation of chromosome duplication during reproduction of the DNA sequences that occurs with cell division, and especially for chromosome crossing over during sexual reproduction. Critics would prefer the project to stop after generating a general genetic map of the chromosomes, from which the DNA in which more interesting genes were located, could be isolated and sequenced. The type of mapping, and techniques for identifying a particular disease-causing gene can take several years of intense investigation, as seen in the tracing of the cystic fibrosis gene (Rommens et al. 1989). At least a more detailed map would decrease the amount of DNA that must be searched for each gene. Also, the DNA outside of genes may have some unknown function. It is currently very difficult to tell from a given DNA sequence, whether it is useful or not.

The project is estimated to cost US$ 3 billion over the next 15 years, to the estimated completion in 2005 A.D. (CIBA 1990). The 1991 government funding in the USA specifically for the human genome project (other research is also working on genetic mapping) is US$66 million, but this figure is expected to increase. However, when one compares this with the cost of the development of a single drug, at US$ 50-100 million, or the space station project at over US$15 billion, or the annual U.S. health care expenditure of over US$ 500 billion, it is a small price to pay for such a large amount of information. There are also multi-million dollar projects in Europe and Japan. Every scientist agrees that the mapping part is well worth the investment.

The initial fear of scientists was would the money come from other biological research or be new money. Within the USA both the Department of Energy and the National Institutes of Health are providing major funding, additional to other biological research (Lewin 1990, Watson 1990).

There are several objectives of genome projects, and there will be benefits as more information is gathered. It requires the establishment and constant improvement of databases containing the sequences of genes, and their location. There are several international databases, and the information should be shared among them (Watts 1990c). The objective is to create an encyclopedia of the human genome, the complete map and sequence. If the information is printed as one character per nucleotide it would require the size of thirteen sets of the Encyclopedia Britannica, without any note of the individual variations in sequence. The data could be stored on half a dozen compact discs. It may be easier to deal in the size of chromosomes, and it was even suggested that each country could be given different chromosomes to work on, to avoid duplication, and to share the costs. The major international effort is centred around the USA, Europe and Japan. There will also need to be technical developments. The actual DNA that will be sequenced will be a composite of different human tissue cell lines, it will not be the DNA of a particular person, but of the species in general.

Coordinated Data-Sharing is Required

The international mapping and sequencing is being coordinated by the Human Genome Organisation (HUGO). Coordination of the international effort is needed, to avoid duplicity of effort which could slow overall progress. The European Commission is also coordinating research in Western Europe. The USA, Japan, U.K., U.S.S.R., and Italy have announced definite programs; France, the E.E.C., Australia and Canada may also join (Watson 1990). There are also needs for the information to be freely shared, though the director of the U.S. National Institutes of Heath Genome Project, Dr. James Watson, earlier threatened that countries that do not contribute funds may not get the information immediately. This remark was targetted at encouraging the Japanese Government to provide funds to HUGO, as well as to their own researchers. However, this has been widely criticised as the information resource belongs to no country, but to the world for its use in medicine. The idea of introducing secrecy would defeat the purposes of coordinating international efforts. The U.K. government is providing 11 million over the next three years, to buy its stake in the use of the information. The idea is that unless they contribute money, governments will lose control of the decisions about how to use the information (Galloway 1990). The most rapid progress will be obtained if data is shared between all researchers. Even if one government declines to support such a project, the information belongs to all people and it is ethical to share it.

There are also private companies embarking on the project (Kanigel 1987), they will be able to patent ways of expressing the genome, though not the genes themselves (see chapter 10). Companies may undertake contracts for research and development with respect to the technical aspects, and they will be necessary, but the final product, the sequence, should not be used for profit (McKusick 1989). Others will be able to obtain the same genes, however it may be cheaper to buy the genes off companies who have found them first. This aspect is controversial, and goes against the idea that genetic information should be freely available. It would be unethical if the information could provide medical therapy if released, as much will do, so should be discouraged. Perhaps such companies could be rewarded with some funds to reimburse their costs, but it may end up being another case of commercial companies making profits out of human disease. In fact, one commonly voiced aim of the U.S. Genome Project is to promote the U.S. biotechnology industry, as they can sell genetic probes that are made from the gene sequences, and new technology. The political aim is to try to put the U.S. Biotechnology industry above that of other countries, especially Japan. As long as the data is open to all, unless there is a complete change in the economic system, biotechnology companies will make money out of the project. There will be some secrecy, but it is desirable that this is kept to a minimum because other data generators will begin to keep their data secret, and overall progress will be slowed. It will undermine the enthusiasm of scientists to participate in the project if they think that other researchers will hide information.

The problem of data-sharing has always existed, but the advent of biotechnology businesses and the patent possibilities, highlighted this. There are several recent examples. The PCR reaction for DNA amplification was developed by researchers at Cetus Corporation. Although it was given out freely for research work, in 1988 a Cetus official announced that they expected royalties from the commercial extensions and uses of this technique. There was objection to this, and the situation has been clarified, so that Hoffman-Roche is licensed for all diagnostic applications, and researchers who use the PCR machine do not need to pay royalties on discoveries that they make using it. The new technology makes replication of results very rapid, which could encourage researchers to delay publication while they get more of a head start in the next stage of the research. Researchers may not reply to request letters, or just reply within a selected peer group. The U.S. Department of Energy has drafted guidelines that stipulate that data and materials must be made publicly available within 6 months of generation. The NIH is not in favour of rules, but encourages researchers to share information, to avoid bureaucracy (Roberts 1990). The results may be seen soon, as coordinated work on chromosome 21, on which over 30 groups are working, with data-sharing. There is an ethical obligation on researchers, especially those using public money, to share data as soon as it is available. If the scientists cannot do this on their own initiative, which is by far the best option, than regulations need to be looked at. There is much collaborative work, and perhaps the global size of the genome project may reverse the trend, out of necessity, if not for data-sharing ethics.

The knowledge gained should be considered as the common property of humanity. There is an existing legal concept that things which are of international interest of such a scale should become cultural property of all humanity. It can be argued that the genome, being common to all people, is a shared asset, and should be open to all. There is also more public concern regarding the patenting of such genetic material, and it could be excluded as discussed earlier. The debate will continue, as companies will naturally desire to want to obtain some information protection for their investment, but they will have to be sensitive to strong public feelings that could easily be aroused, which as argued, has an ethical backdrop. The idea that the human genome sequence should be public trust and therefore not subjected to copyright was also the conclusion of the National Research Council of the USA (NRC 1988), and by the American Society of Human Genetics. This idea would also include the option that the donor of genetic information, in terms of a cell line, should be able to make that information publicly available, which is usually a reasonable interpretation of the motives for patients to provide material for medical research, the motive to aid humanity in general rather than a commercial interest.

There have been two major U.S. Reports on this project, one by the Office of Technology Assessment (OTA 1988a), and another by the National Research Council of the National Academy of sciences (NRC 1988). They both recommended that a map of the human genome is made prior to full scale sequencing. While mapping will benefit from improved methods, sequencing requires much improved and cheaper technology. A map is also essential to efficient sequencing so that a library of DNA fragments can be systematically sequenced. We are still in the early stages, and a variety of small scale mapping projects are being supported so that the better methods can be allowed to develop from these. All the data can be made to be interchangeable, by tagging of marker sites by unique DNA sequences, called sequence tag sites (STS) as markers. This will avoid the need to exchange different clones of DNA between laboratories, as each laboratory can use the sequence marker as a starting point (Roberts 1989). The human linkage map is well on the way to completion, the question is how big the gaps between markers should be. The distance used is called a centi-Morgan (cM), and one cM is equivalent to two markers being separated from each other in chromosome crossing over in normal reproduction 1% of the time. The actual physical length of 1cM varies, being approximately 1 million base pairs. The linkage map will be made with an average spacing of 2cM, with maximum gaps of 5cM. The map will of course be improved as the gaps are filled in. Some chromosomes are already covered by markers at 1-5cM intervals. Different research groups have begun to concentrate on different chromosomes in order that they can all have the complete map in a shorter time. The five year goal of the NIH program is construct a map with STS markers spaced at about 100,000 base pairs, and to assemble overlapping contiguous cloned sequences (called contigs) of about 2 million base pair length, of the entire human genome. From this physical and informational library system, the sequencing can be started. Several different methods are being used, as it is uncertain which library-making and marking procedure will be most efficient.

Model organisms are also being studied, and the genomes of other complex systems are being sequenced, such as nematode worms (C. elegans, 100 million base pairs), Drosophila melanogaster (150 million base pairs), mustard (Arabidopsis thaliana, 100 million base pairs) and the mouse. In Japan a rice genome project is commencing. The techniques developed will be transferable between different organisms. Another point is that without comparative sequences we may not be able to understand how the human genome works, how genes are regulated in a coordinated way during the lifetime of an organism. The initial target is the development of new technology. Data management technology must also improve, such as programmes to search the DNA sequence libraries, using advanced computing technology.

There had been talk of giving different countries the tasks of sequencing different chromosomes to avoid duplication, however such as system was considered impractical given the way scientists work. Also most chromosomes have already some preliminary map. There are actually 24 different chromosomes that need to be sequenced, the 22 autosomes and the X and the Y chromosomes. Many researchers remain more interested in pursuing specific disease-causing genes. There are only a few chromosomes that are being extensively mapped at the moment, these include chromosome 21, which is small and contains the Alzheimer's susceptability chromosome 7, and chromosome X. Other chromosomes, such as number 8, which have few known genetic diseases linked to it, are poorly known. The coordinators, in this way HUGOa plays a useful role, can point out the number of existing projects on each chromosome to those who submit research proposals mapping such chromosomes. National medical research funding bodies can possibly reject funding applications that are overlapping. To duplicate work is important for confirmation, but certain areas may have a dozen teams working at the same goal which is a waste of effort.

Ethical Implications

There are major applications and implications of such work. It will be a huge resource of information for medicine in the next century. There will be much useful information arising prior to the completion of the project, as many disease causing genes are sequenced and the mutations characterised. There have been many potential ethical and legal problems raised (CIBA 1990), especially from the scale of the information (Friedmann 1990a). The possibility of mastery and control over the human DNA raises the issue of genetic selection (OTA 1988a). It would be possible to develop DNA probes to diagnose any known genetic disorder, and also would be easier to characterise new disorders. This is important for genetic screening, and therapy of diseases as currently most disease causing genes have not been identified or located. The gene responsible for each genetic disease will be isolated. It will also be possible to expand the number of human proteins that can be made by genetically-modified organisms, which would allow conventional symptomatic therapy for many more diseases, which could be supplemented by somatic cell gene therapy when appropriate. It would also expand our basic knowledge of human biology, which allows medical treatments to be developed. It is obvious that within the next few decades medicine will undergo a major change, this is the beneficial side of the extra knowledge. The amount of new knowledge is hard for us to comprehend, it will take decades to process it all, but it offers the potential understanding of all genetic diseases sometime during the next century. We should remember that understanding the genetic mutation that causes a disease is very different to being able to treat it, for example it has been thirty years since we knew the mutation that causes sickle cell disease, but we are still developing effective therapies.

We must also be aware that this new knowledge, which we must accept will be known probably within fifteen years, will allow ideas of eugenics to be explored. We need to maintain a distinction between diagnosis and treatment of disease, and selection for desirability. This fear has lead to calls for research into the social and ethical implications of this research. The techniques that we possess now, and will possess in the next twenty years are much more powerful then the techniques used early this century. We will get some idea of the possibilities by looking at the animals that can be made using the new genetic techniques in the next few years.

The ethical debate must focus on how to use the new information, rather than on whether to discover it. Most religious approaches support the rationale for obtaining better genetic information, which can be used to alleviate human suffering (Kimura 1990). The decisions to progress, have already been made, and there are certainly many benefits from the project. The question of fairness in the use of genetic information with respect to insurance, employment, criminal law, adoptions, the educational system and other areas must be addressed. The impact of the information on the individual is a different perspective. We must avoid stigmatisation or ostracism, and labelling in general, and look at the individual psychological responses. The ownership and control of gGenetic information, and the consent to use such information must be addressed. There will need to be more serious consideration given to personal reproductive decisions in the future, making life more complicated while hopefully improving its quality. Some of these issues have been discussed in former sections of this book, and obviously more attention is needed. We should note that the amount of information obtained will overwhelm existing genetics services, and geneticists. More training of genetics (as well as ethics) will be required for physicians and health care workers.

The time is right for much discussion regarding how we use the information. It is proposed that in the USA from 1991, town meetings may be held to inform the general public about the human genome initiative, and to solicit opinions on the ethical, social and legal issues that it raises. The human genome project has even found its way into French school books, and it is important for such widespread education to be available in a way that the public can understand it. An adequately prepared lay community is the best way to ensure that misuse of genetics does not reoccur. There should also be education to show that despite all the information, we should not expect disease to be cured within twenty years, and it will not be a panacea for the world's woes.

It is pointless to bury our heads in the sand, as the knowledge will come. The question is how to use it for proper stewardship. There are dangers in any large scientific projects, that they take control of the people, in becoming the sole ideal for progress. We have seen this in the past with the Manhattan project, and the Apollo project. From the initial response to the human genome project, this is also happening here (Annas 1989).

The topics addressed in last three chapters, and this one, on the use of genetic information are the applied use of this information. The Human Genome Project itself will succeed, in the absence of any wider catastrophe. We need to solve some of the existing dilemmas before the information is overwhelming. Rather than delaying the research, it means we must no longer delay public discussion of the issues. Long term health plans must be devised with this in mind. For example, the recent U.S. Presidential Office Health Care plans until the year 2,000 do not include the establishment of coordinated genetic screening services for prenatal diagnosis, let alone incorporating them into a National Health Service. These developments are not only desirable, but inevitable, and the sooner governments realise this the less problems will have accumulated when the time comes to switch to national health schemes. The injustice of private health care schemes will be accentuated. Like it or not, ethics in terms of justice may become a political issue in some countries.

Fears of Genetic Determinism

There will be a change in attitude to ourselves also, and gGenetic determinism might become popular, the idea that the answer to our problems lies in the genes. Determinism is the idea that there are causal mechanisms for any action. By tracing the pathways between genes and behaviour we may start to get a determinist picture. Already some genetic work in psychiatry can aid that picture, which has only limited truth. For instance the pattern of behaviour classified by psychiatrists as sensation seeking, involves a disposition to gambling and drinking, and can be correlated with low levels of activity of an enzyme platelet monoaminase oxidase. Of course there may not be any causal relationship, but people seeking an explanation or not totally informed, can easily jump to conclusions. A danger with simple-minded adherence to genetic hypotheses for behaviour is that it oversimplifies the complex interaction of genetics and environment. There may also be elements of homosexual behaviour that cause predisposition to it from childhood experience or genes, this could lead to labelling of such people and the belief that such behaviour is unpreventable. In the extreme determinism eliminates the idea of genuine choice, leaving no room for the belief that we can create, or modify ourselves, or that we can make moral choices. What people should already have seen from the genetic knowledge that we have, is that most behaviour does not follow patterns in our genes, as we can change in our lives very much. It is thought that perhaps a third of the genes are brain-specific genes, maybe more, and the genome project promises much for that area also. The question whether higher human attributes are reducible to molecular sequences is a controversy in philosophy of biology

The knowledge of human genetics will make scientific understanding of human life much more sophisticated. We may be able to understand the degree to which genetic factors control behaviour. If the information reveals that individuals have less options for variance then they suppose, then a determinist view will emerge. There may be alteration in social customs, especially if the information is misunderstood by the public as occured at the beginning of this century. For instance your gene profile might say that you can only do an undergraduate degree in history, and discourage you from doing anything more difficult, or from anything easier. However, our genes are not that deterministic, we only have to look at the variety of people in different social clubs. In many cases, changing social policy and encouraging individuals to alter behaviour will be a better remedy than using genetics.


Our Future Obligations

The other side of the argument, is whether society will allow individuals to have free choice over the use of genetic manipulation when there is no medical reason for it. Society already prevents attempts at medical therapy if there are possible risks, in the controlling of the use of somatic cell gene therapy. In the case of somatic cell therapy, an existing individual with a problem exists, which involves some healing obligation to cure. In the case of germ-line manipulation however, there is no existing individual, but unless the therapy is performed (assuming the parents reject the use of donor gametes or child adoption), there will be an individual with a problem. In the case of many diseases, it is best if the gene defect is fixed before it has a chance to damage the fetus/child's development.

There are various arguments used against genetic intervention which has no therapeutic value, and some of these have been already outlined. It would be a waste of resources, may present risks to offspring, it will promote a bad family attitude, will be harmful support of society's prejudices and may reduce social variability. It will probably not have any significant affect on genetic variability as there will be plenty of alternative healthy alleles. There could also be the idea of a natural genetic autonomy, that we should let the genes come together naturally, and let the individuals develop their genetic potential without unnecessary interference by parents or society. While we can justify the curing of disease, we can not justify enhancement engineering. A criteria for transgenerational ethics is that not only must a gene alteration be safe, but it must be good therapeutic sense in many generations. There must be unquestionable objectives and benefits, for many generations.

A common feature of these issues is that we need to consider the effects of technology on future generations. We have a responsibility to future generations. The beneficiaries and those at risk may not yet be existing. We have an obligation to the future (Rawls 1971, Blank 1984). The human genome project raises some similar ethical and legal issues to those in current genetic screening, such as confidentiality of the results. However, it will lead to screening on a huge scale, for many disease traits and susceptability to disease. It is important that we deal satisfactorily with the test cases, before we are faced with all these new information. The technology may change the way we think.

Our traditional view of morality only involves short term consequences. Human action is seen as only having a small effective action range. Moral liability is limited by what is unenforcible. If another agent intervenes, or something unexpected happens, it is not considered our fault. Genetic engineering changes our moral horizon. For that we should be very grateful, as for too long we only examined short range effects.

We can see similar problems emerging with the environmental crisis. In this way discussion of germline genetic engineering contributes to our ethical thinking. The ethics of long range responsibility are needed. It implies that there is a moral imperative to obtain predictive knowledge and data about the wide-ranging possibilities of some action. Secondary consequences may be sufficient to prevent the primary action, even when the primary action may be good. This imposes a restraint on the use of technology. In this respect this ethics is important for public policy decisions, beyond the physicians concerns with each patient, or the scientists concerns with increasing yield of some crop variety.

It means that researchers may be held accountable for secondary consequences of their research. Of course it may be very difficult to predict what will happen in the future, the social pressures and thinking are already very distinct between different countries. If social ideas change, then so may the pressures, such as the desire to use genetic enhancement. We need to ensure future generations retain the same power over their destiny as we do, while benefiting from the culture and technology we have developed.


Please send comments to Email < Macer@sakura.cc.tsukuba.ac.jp >.

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