You have to admit, it's quite a love line:

I wish to believe in immortality – I wish to live with you forever.

These words were penned by a love-stricken English poet, the erudite and youthful John Keats. The target of this articulate affection was Fanny Brawne, a genteel woman raised in wealthy pre-industrial London. As sweet as his sentiments may have been, Keats didn't live long enough to give her or us a happy ending. The reason was tragically biological. Keats' lungs were laboring under the occupation of a few billion Mycobacterium tuberculosis bacteria, the causative agent of tuberculosis. The poet may have contracted the disease from his family, having watched both his mother and his older brother die of ‘consumption.’ Eventually, the disease involved his own life, abridging it to a mere 26 years.

Keats had a professional as well as personal interest in tuberculosis. Before he was a poet, he was a physician, trained at the famous Guy's Hospital in England. Keats did not turn to professional writing until the final three years of his life, inspired in part by Brawne, in part by his familial losses. Those three years would be filled with a biological wrestling match between his brain and the bacteria, between his desire to obtain immortality in writing, and his eventual desire for suicide.

Keats first suspected he might have contracted the dreaded disease during a visit to Scotland.

Concern about the state of our environment has slowly worked its way up the political agenda over the last decade or so. This new awareness exists on many levels: there are global issues such as climate change, local problems such as traffic congestion, as well as health worries caused by toxic waste and air pollution.

Biological processes, such as photosynthesis, helped to shape our environment in the early days of evolution, as we shall see in Chapter 12. The aim of environmental biotechnology is to use the transforming power of biochemistry – driven, of course, by DNA – to help to create an environment that we would be proud to leave to our grandchildren.

There are two main ways in which biotechnology can soften the impact of human activity on our planet. It can help in the provision of energy and material resources, and in the destruction of pollution.

Trapping energy from the Sun

As the world's population grows, so do people's aspirations. Hence many people in developing countries want the cars, fridges and other objects that we take for granted in the Western world. At the same time, they also want to develop their industries to generate income and a higher standard of living. Inevitably this will result in increased energy consumption – from more electricity to drive domestic and industrial appliances to more fuel for heating and transport.

Today the commercial energy market is dominated by coal, oil and gas – the fossil fuels.

The human genome project, DNA testing, gene therapy, and genetic engineering … there is no shortage of news about the gene revolution. This book aims to take you behind the headlines and explore the fast-moving and fascinating world of molecular biology.

In the first part of the book, I have tried to convey the power and uniqueness of the DNA molecule: how it was discovered, what it does, and where it came from. This leads into genetic engineering and its potential. In a very real sense, there is nothing special about gene transfer – it has been going on for billions of years. Its potential comes from humans, rather than the blind forces of evolution, being at the controls. The applications of genetic engineering and related technology that have attracted the most publicity – gene testing and therapy, and transgenic animals – are considered next.

But genetic engineering is just one aspect of biotechnology (although the two terms are often used synonymously); in the third part of the book I try to look at the wider world of biotechnology, as well as that of genetic engineering – as applied to plants and the environment.

Critics say that there is an overemphasis on DNA in biology, leading to a kind of reductionism, which has alienated the public, and some scientists, from its benefits. In the last part, I have tried to put DNA in context by looking at some other new ideas that have emerged in biology over the last 20 years or so.

Introduction

Can genetics be confused with eugenics? This is one of the questions raised by the Nuffield Council on Bioethics in their report on the ethical issues of genetic screening, which suggests that the ‘potential for eugenic misuse of genetic testing will clearly increase’ (Nuffield Council on Bioethics, 1993). In the report, eugenics is defined as the selective breeding of some members of the population and the elimination of undesirable individuals, which found its worst expression in the racial hygiene policies of Nazi Germany. Britain, however, has a long history of a eugenic movement involving many leading members of society, including members of the medical establishment, a movement that continued through the 1950s and 1960s. This chapter investigates the British eugenic movement as one way to help address the difficult questions emerging today from the ‘new genetics’.

We examine the origins of eugenics in the early twentieth century in the work of Francis Galton, who was a cousin of Charles Darwin. The middle-class concern with social problems of the 1920s and 1930s, unemployment, pauperism, alcoholism and the decline of the nation, found expression in eugenic policies on population control. Scientists, too, participated actively in debates on the hereditary aspects of social problems.

Introduction

Over the past 25 years the new reproductive technologies (NRTs) such as in vitro fertilisation (IVF) and the new genetics together have aroused my concerns. This may seem odd to molecular biologists, geneticists, embryologists and obstetricians, whose specialisms differ one from the other and who for the most part work independently of each other; but a woman could not help noticing that the first applications of the new genetics impinged on pregnancy and birth – in prenatal screening and the offered abortion for fetuses found to be impaired. This represents a great change from the way in which pregnancy, birth and possible disability were previously understood. Consequent psychological problems for women were likely and seemed obvious. Yet what thought was given to the problems was commonsensical rather than systematic or scientific – and derived from men's, not women's, common sense.

To a sociologist it is axiomatic that a birth is a social as well as a biological event; the arrival of a new member of society changes the social arrangements around it.

Epistemology, ethics and genetics

Developments in genetics ‘pose challenging questions for the application of traditional legal principles’ (Kennedy and Grubb, 1993). This much was recognised, for example, at the Asilomar conference in 1975, where a group of molecular biologists recommended a moratorium on genetic manipulation while arrangements were made to regulate recombinant DNA techniques (Maddox, 1993). Without precedent, the scientific research community was inviting regulation from the legislature for its own activities. Indeed, writing in 1971 James Watson (the elucidator, with Francis Crick, of the structure of DNA) had suggested, of the possible developments in human reproductive research, that techniques for the manipulation of human eggs in vitro were likely to be in general medical practice, capable of routine performance in many major nations, within some 10 to 20 years, and that international agreement was a preferred method of control. On some matters there might even be ‘a sufficient international consensus… to make possible some forms of international agreement before the cat is totally out of the bag’ (Watson, 1971).

The particular difficulties that lawyers and ethicists will want to address are the functional analogue of the difficulties that the genome project discloses in general:

Introduction

The applications of human genome analysis (HGA) are numerous and diverse and are being implemented with increasing rapidity as progress in genetic technology and knowledge escalates. A predominant question, frequently being expressed in both Europe and the USA, is one that addresses the problem of whether advances stemming from HGA will be used with due regard to upholding established moral principles and human rights or whether, with insufficient awareness of the ethical issues involved and inadequate regulation, there is a real danger that these might be violated. There are undoubtedly important potential benefits to be gained by both individuals and society but, at the same time, there is some anxiety that serious, adverse social and psychological consequences might arise unless the new knowledge is used ethically.

This chapter will identify a wide range of issues that have already arisen or might feasibly be encountered in the future as the result of HGA. These will be discussed from the standpoint of ethical principles with the intention of illustrating that, overall, society has much to gain and that many of the possible hazards may be overcome provided that professional and public awareness of ethical implications is promoted and safeguards are instigated to ensure the amelioration of harm.

What is human genome analysis?

Human genome analysis is the resolution of genetic information that is encoded within the entire complement of human hereditary material.

It is now approaching four years since we completed work on the original edition of The Troubled Helix. How have things changed since? As we commented then, each week brings reports of the identification and cloning of new genes, but as we also said, from the perspective of families these have been little more than promises of future developments that might alleviate some of the burden of inherited disease that some carry. Both comments remain accurate today. This year has brought the inauguration of the American Society for Gene Therapy and it is thought that a couple of hundred gene therapy experiments may be underway, but it is unlikely that more than a handful of people have yet benefited from these techniques. This number will, of course, rise but there is every indication that it will be a much slower and rockier road that many researchers and their funders would even now want to admit publicly.

Direct genetic testing has also proved rather more complicated than some of the earlier examples, such as that for Huntington's disease, suggested. This is well illustrated by what has happened in the testing for the two genes that have dominantly inherited mutations associated with breast and ovarian cancer, BRCA1 and BRCA2. BRAC1 was cloned in late 1994 and BRCA2 soon followed; however, today most of those who on the basis of their family history would appear to be at high risk of carrying mutations of one or other of these genes still cannot be offered genetic testing because no mutation can be found in their family.

Introduction

Genetics concerns families and kinship. It is the study of the ways in which heritable characteristics and conditions are passed from parents to children through the generations. As the new genetics develops, the possibilities of describing the gene mutations that an individual may carry and may pass to children are increasing dramatically. This new knowledge and the ways in which it is employed may have profound consequences for family life and relationships.

The public's knowledge and beliefs about inheritance have not arisen de novo with the coming of the new genetics, or even with Mendelian genetics at the turn of the century: they have long been part of family culture. Much family talk is about particular characteristics of family members, who these may have been acquired from, and who they may be passed to. Witnessing family members greet a new baby demonstrates the important process of ‘placing’ the new baby in terms of characteristics shared with forebears. Increasingly, we have photographs and other visual evidence of the appearance of our forebears and we use these to point to similarities and differences. In my own family I am said to get my nose from my mother's family but have a temperament more like some of my father's male relatives.

Introduction

Testing healthy children to identify genetic conditions has been possible for many years by clinical examination, blood tests and other investigations that recognise the relevant phenotype. Examples include the recognition of children with type I neurofibromatosis by examination of the skin, the biochemical recognition of infant boys with Duchenne muscular dystrophy, the identification of unaffected carriers of haemoglobin disorders (e.g. sickle cell disease) by haematological tests, and the identification of some asymptomatic children or adolescents with autosomal dominant polycystic kidney disease by ultrasound examination of the kidneys.

The recent development of molecular genetic technologies has transformed the situation by greatly extending the possibilities for genetic testing. Molecular genetic methods test directly for the relevant gene. These tests can be carried out at any stage of life from conception onwards, using any nucleated tissue, for example white blood cells or a mouthwash sample of oral epithelial cells. There is usually no need to test a tissue affected by the disease process. Many genetic tests are now available for inherited diseases for which there had previously been no diagnostic test. Such tests can identify children who are likely to develop genetic disorders in adult life, and can also identify those carrying recessive disease genes, which have no effect on the health of carriers but may have implications for the health of carriers' future children.

This chapter addresses controversial issues raised by the possibility of testing children that are (apparently) healthy (Harper and Clarke, 1990).

The significance of genetics would have remained purely in the scientific realm had it not begun to affect decisions made by and about individuals. The inseparability of clinical genetics from decision-making is illustrated in reviews of the literature on genetic counselling, which are devoted in large part to studies about the process and outcomes of counsellees' decisions (Evers-Kiebooms and Van den Berghe, 1979; Reif and Baitsch, 1985; Kessler, 1989). Decision-making was recognised as one of the key elements in genetic counselling (Fraser, 1974), and was further emphasised by Bringle and Antley's (1980) elaboration of genetic counselling into a model for counsellee decision-making. Kessler (1980) considered the increasing importance of decision-making in genetic counselling as part of its general shift away from eugenic values towards a psychological paradigm. The underlying logic behind these views is that individuals should be appropriately informed about their genetic risks and behavioural options to deal with those risks, and that they would use that information vigilantly to choose among the alternatives made available by newly developed genetic technologies. Before genetic counselling, most people do not even know about these options: they do not perceive the situation as a decision until explicitly told it is by the genetic counsellor (Beeson and Golbus, 1985).

Putting individuals in a situation of choice about genetic risks fits the broader trend of the evolution of behavioural mechanisms that serve to regulate chance events – a trend expressed most vividly in the growing importance of individual choice over reproduction (Miller, 1983).

The rate of change in the field of the new human genetics appears hectic. Each week brings reports of the localisation and cloning of new genes. The accelerating rate of change is well illustrated by the history of research on hereditary breast and ovarian cancer. Although it has been long accepted that a family history of breast cancer indicates some increase in risk for all women in the family, it was generally assumed that this was the result of many genetic and environmental factors working together. Few people believed until very recently that it was likely that single-gene effects were significant. In fact, as long ago as 1866, Broca, in his Traité des Tumeurs, published his wife's family tree showing ten women in four generations who had died of the disease. While today this pedigree would be interpreted as evidence of an autosomal dominantly inherited susceptibility, at the time its significance was not understood. It was not until 1990 that Mary-Claire King and her colleagues used genetic linkage analysis to identify a location on chromosome 17q for a gene that was named BRCA1. This observation was soon confirmed and extended to include ovarian cancer. By the time work had begun on this book, linkage testing for BRCA1 was just starting to be offered to members of suitable families. Indeed, one of the personal accounts in the book describes what may well have been the first occasion on which the results of linkage testing were used in making a decision about treatment.

There is always a problem when new medical technologies lead to clinical services for which we have no or little evidence of their impact. The desirable approach is to carry out clinical trials to determine their effectiveness and safety. Predictive genetic testing is a technological development with possible psychological and social effects that have been much discussed. Because predictive testing can be offered to children, as well as to adults, the discussion has been wide-ranging, encompassing issues such as competence to give informed consent, the rights of the child and autonomy.

The complexity of these issues does not mean that policies should be formulated without the backing of relevant research. Indeed, it could be argued that such testing should only be offered as part of a research protocol determining its effects and the circumstances under which it is most effective and least harmful.

There are three general approaches to the clinical introduction of genetic developments that can be identified in past practice. One is to herald caution, and keep the debate within professional circles. The second is to consult widely, seeking the opinions of potential users of new services and the general public. The third is to promote rapidly the research that will address the questions of psychological and social impact. In Chapter 7, Clarke and Flinter emphasise the first approach; I shall discuss the second two approaches.

The current view of clinical geneticists is summarised by Clarke and Flinter as follows:

Introduction

With the rapid rate of discoveries in human genetics and their increasing clinical application, the demand for genetic counselling is increasing. We know little about what makes for effective or efficient genetic counselling. This chapter will focus upon the methodological issues that need to be considered if we are to further our understanding of the effective ingredients of genetic counselling. In doing so, we will necessarily touch upon decision-making in the counselling context. This is, however, dealt with in more detail in Chapter 3.

The attempt to evaluate genetic counselling requires a definition of its aims. Broadly speaking, genetic counselling is a communication process aimed at helping people with problems associated with genetic disorders or the risk of these in their family. Its most uncontroversial goal is to improve the quality of life of the families that seek such help (Twiss, 1979).

The central issue in genetic counselling has been described as ‘the provision of “objective” information from the counsellor and its interpretation by a patient’ (Shiloh and Saxe, 1989). Other definitions have included decision-making. One such example is: ‘the essence of genetic counselling is the counsellor's ability to transmit genetic information about an inherited disorder of concern to the counsellee(s) so that it will be incorporated into decision making’ (Falek, 1984). A widely quoted, and comprehensive, definition of genetic counselling was provided by Fraser (1974, p. 637).