How Distinctive is Genetic Information?

Pergamon

Stud. Hist. Phil. Biol. & Biomed. Sci., Vol. 32, No. 4, pp. 663–687, 2001  2001 Elsevier Science Ltd. All rights reserved. Printed in Great Britain 1369-8486/01 $ - see front matter

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How Distinctive is Genetic Information? Martin Richards* There is extensive discussion of the ethical, social, economic and political issues associated with the use of technologies based on DNA techniques. Many of these debates are premised on the assumption that DNA, and the genetic information that may be derived from it, have unique features which raise new social and ethical issues. In this paper it is argued that several of the features associated with DNA which are sometimes regarded as unique are shared with other biological materials. Others owe more to the cultural image of DNA and some of the metaphors used to discuss it in biology and in wider debates than to the biological properties of DNA. The paper discusses the concepts of genetic material and genetic information and the social construction of DNA in relation to forensic DNA databases, paternity testing and genetic testing for disease. The paper concludes by suggesting that there are seven areas where issues related to DNA and genetic information are at least relatively distinct.  2001 Elsevier Science Ltd. All rights reserved. Keywords: Genetics; DNA; Genetic Information; Metaphors of DNA; Genetic Material; DNA Technology.

An exact determination of the laws of heredity will probably work more change in man’s outlook on the world, and in his power over nature, than any other advance in natural knowledge that can be foreseen. William Bateson (1900).

1. Introduction DNA technologies have a very wide variety of uses of medical and social significance. These include the development of predictive tests for Mendelian diseases, the creation of forensic DNA data bases, and tests for confirming family relationship in the context of immigration control and child support payments. These, and many other uses of these technologies and the information they can produce, have led to much discussion about the ethical, social, economic and political issues

* Centre for Family Research, University of Cambridge, Cambridge CB2 3RF, U.K. (e-mail: [email protected])

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involved. Debates have often focused on issues of confidentiality and privacy, and the ways in which DNA and genetic information is obtained, stored and used in clinical research and practice and in many other social contexts. Legislative systems and other arrangements exist for the control and governance of the use of molecular genetic information and material in many countries (See Knoppers et al., 1998).1 Many of the debates about the use of these new technologies appear to be premised on the assumption that DNA and the genetic information that may be derived from it have unique features which may raise new social and ethical issues distinct from those related to other biological material, issues that, in turn, may call for new forms of regulation. In this paper I will explore the concepts of genetic material and information and the extent to which these may be regarded as different from other biological materials and information. I will argue that several of the features associated with DNA and genetic information are less distinctive than is often supposed.2 Some perceptions of DNA may owe much to the cultural image that it has acquired through the ways in which biologists and commentators have talked up the power and potency of this molecule which has become an icon of our society (Nelkin and Linde, 1995). More subtle in their effects, but perhaps even more persuasive, are the metaphors used in the biological sciences and in popular accounts and debates about science, which accord a unique, and in some ways misleading, status to the genome (Pollack, 1994). In analysing what may, or may not, be distinctive about uses of DNA technology, it will be important to draw a distinction between genetic material, DNA, and the genetic information that may be derived from this and other sources. In some situations the problematic issues arise because DNA analysis, rather than other kinds of analysis, has been used to produce information, but the information itself may not raise new issues. In other cases it is the information that can be produced through DNA analysis (or sometimes other means) that is the key point. As I shall describe, forensic data bases are an example of the former situation, while some predictive genetic testing for Mendelian disease falls into the latter category. 2. Genetic Material The term genetic material refers to the DNA of the chromosomes and mitochondria3 which together with other essential biological materials are transferred

1 A useful database of legislation and guidelines in many countries is provided by The Genetics and Society Project at the University of Montreal, Canada (http://www.humgen.umontreal.ca). 2 As others have done, for example, Murray (1997), Holm (1999) and Zimmern (1999), in challenging concepts of ‘genetic exceptionalism’. 3 The mitochondria are small organelles in the body of cells which play a vital role in energy metabolism. Mitochondria reproduce within the cell and are transmitted between generations via egg cells. They have their own DNA. Mutations of mitochondrial DNA can occur and may lead to serious disease. It is thought that early in the evolution of multicellular organisms mitochondria developed from bacteria that established a symbiotic relationship in the cells of early life forms.

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between generations as the sperm and egg.4 DNA is an enormously long molecule (at least by the standards of most) made up of a sequence of nucleotides. These come in four kinds, A (adenine), T (thymine), C (cytosine) and G (guanine). Parts of the DNA molecule are made up of genes and the rest is what biologists have called junk, parasitic or selfish5 DNA—DNA of uncertain function. The genes make up the so-called genetic code—sequences of nucleotides that specify the sequence of amino acids in the synthesis of proteins. The sequence information from the DNA is not translated directly into amino acid sequences, but there are intermediate steps involving RNA (a long chain molecule similar to DNA). In passing we should note—and it is an important point that we will come back to— that the DNA cannot do anything on its own. It is a relatively inert chemical. A complicated biochemical system is required to ‘read’ the sequence of the genes, ‘interpret’ these and express them as amino acid sequence of proteins.6 DNA has a number of properties which are significant for the social and medical purposes for which DNA testing may be used. Every cell in the body is derived from the initial cell formed by the fusion of egg and sperm, and each7 contains copies of the chromosomes inherited from the mother and father.8 The chromosomes are made up of a tightly coiled DNA molecule and associated proteins. This means that DNA can be extracted from any cell7 in the body and, whatever its source from the body, it will have exactly the same nucleotide sequences (and genes); any cells can stand for the whole of the body from which it has come.9 The same is true, of course, for cells that we shed—flakes of skin, hairs, drops of 4 In some contexts the term genetic material is used, misleadingly, to refer to the gametes. This is the case in the UK legislation regulating assisted reproduction, The Human Fertilization and Embryology Act 1990 (Johnson, 1999). 5 This terminology is not unrelated to issues of genetic essentialism which will be discussed later in this paper. 6 We should also note that there may not always be a direct correspondence between a particular sequence of DNA and the sequence of amino acids in a protein. Some genes overlap one another, and in other cases in ‘reading’ of a gene some sequences may be edited out. The discovery of these and some other complications of the system have made the concept of the gene somewhat problematic (see Beurton, Falk and Rheinberger, 2000; Keller, 2000). 7 Not quite all. Red blood cells lose their nuclei, and so the chromosomes they contain, during the process of their development. This is a confusing exception as blood samples are often used for DNA testing. But here the DNA is derived from the white blood corpuscles. 8 In classical biology it was assumed that it made no difference whether a particular gene variant was inherited from a mother or a father. We now know this is not the case. Genes may be chemically inactivated in the process of gamete (egg and sperm) formation before they are transmitted to a child. The genetic code remains unchanged but some genes become non-functional. This process is known as gene imprinting. Because imprinting is different and complementary in mothers and fathers, mammalian reproduction requires a parent of each sex. This is not a limitation in sexual reproduction, but it becomes a vital factor when considering, for example, the development of reproductive technologies for samesex couples (Johnson, 2001a). 9 Again, as they say in the advertisements, exceptions may apply. Somatic mutations (those occurring in the cells in the body and reproduced through cell division), as those that lead to tumour formation, change the nucleotide sequence that we inherit. But because, by definition, these are not mutations in the germline (sperm or eggs) they are not passed to the next generation. However, if a mutation occurs in cells that produce eggs or sperms or in the gametes themselves (a germline mutation) that may be passed on to children.

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blood, sperm, cells in our faeces and urine—all of these can be used as sources of DNA. As we move around, we leave in our wake fragments of our body which contain copies of our DNA. DNA is a relatively stable molecule and it does not break down easily. This means that the sequence of nucleotides may be preserved so that very old fragments of dead tissue containing chromosomes can be used as a source of DNA for testing. Dried spots of blood left on clothing many years before, the blood collected by the heel pricks from new-born babies for screening tests and stored by hospitals (Guthrie Tests: see McEwen and Reilly, 1994) and ancient human remains or pathology specimens (Wertz, 1999) can all serve as sources of DNA for sequencing. Fundamental to DNA technologies is the ability to clone—replicate—DNA molecules, or parts of them. Just as each cell when it divides makes a new set of chromosomes with identical copies of all the DNA molecules for the daughter cell, so in the laboratory it is possible to make multiple copies of DNA molecules. In principle, a single molecule can be copied indefinitely. The second key step in the technology is the ability to sequence DNA—to determine the order of the nucleotides in the DNA molecule—the As, Ts, Cs and Gs of the so-called genetic code. While we all carry the same set of genes, there is some variation of the nucleotide sequences in genes from person to person and even more variation in the sequences of the ‘junk’ DNA. Some variation in sequences in genes may make it impossible for a functional protein to be produced. These variations are generally referred to as mutations—rare changes, which may lead to genetic disease; the diseases being caused by the absence of a functional protein. Other variation in sequences does not disrupt function in quite such a drastic way but may lead to variations in the protein structure and the ways in which these then function. These (more or less) benign variations of a gene are known as alleles or polymorphisms. This variation in the sequences of genes, and the even wider variations in the other DNA, means that we all—at least if we are not an ‘identical’10 twin—have a unique DNA sequence. At a rough estimate there may be, on average, a million differences in the DNA sequence between two unrelated people. The obvious implication is that DNA sequences can be used to characterise an individual and to trace relationships between (blood) relatives by comparing the similarity, or otherwise, of their DNA sequences. It is often useful to think of variations in DNA sequences at three levels, the individual, that of the family or kinship and that of the particular population or community. So, in summary, what are the major uses can be made of DNA technologies? 1. By comparing the sequence of an unidentified specimen of DNA with the sequences of named samples, DNA can be used to identify individuals. 2. Comparisons between individuals can reveal their degree of genetic or ‘blood’ 10

The significance of these quotation marks will be discussed below.

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relatedness. DNA can be extracted from excreted or discarded body fragments (cells) or from remains of long dead individuals for these purposes. Only very small quantities are required. 3. Population groups can be characterised in terms of particular gene variant frequencies and compared in these terms. 4. Identification of gene mutations associated with Mendelian (single gene) diseases can be used to diagnose or predict (with varying degrees of accuracy) the future onset of these diseases or the likelihood that they may be passed on to children. 5. Common gene variants can be identified. A few of these are known to be associated with increased or reduced risk of developing common ‘complex’ diseases, the response to drug treatments or sensitivity to some chemicals (which may, for example, be used in industrial processes). In addition to these uses which are relevant to the issues discussed in this article, DNA technology has extensive uses in medical and other research and practice. These include gene therapy, a topic which is much discussed and the subject of a large research effort but which currently remains a largely elusive goal. Another very different use, rapidly growing in importance, is the production of DNA in the laboratory for use as an identifier for objects (such as paintings and antiques) and liquids (such as crude oil cargoes). However, further discussion of such uses is beyond the scope of this paper. 3. Genetic Information The special status that may be accorded to genetic information arises, in part, from the ways in which DNA is often conceptualised in modern biology. Contemporary biology is often very genocentric. Not only do genes usually hold centre stage as the stuff of inheritance but, for instance, it has become increasingly fashionable to see evolution not in terms of the changes in attributes of descendants over generations but as the genes that may, or may not, be passed on to posterity. Genes, it is said, are the ‘blue prints’ for future lives, or, as President Clinton put it in more elevated terms as he welcomed the publication of the first draft of the human genome sequence, genes are ‘the language in which God created man’.11 Genes, it would seem, are us. In terms of this genocentric world, DNA (or at least the parts of the molecule not regarded as junk) is genetic information. However, to gain a little more clarity about what is meant by the term genetic information, we need to put some conceptual space between the material of DNA and the notion 11 A phrase he borrowed from Francis Collins, the Director of the US National Human Genome Research Institute. A number of commentators have pointed to the similarities between the ways in which some biologists write about their views of genetics and evolutionary theory (and the views of other groups they disagree with) and the language of Christian evangelicalism (for example, Nelkin, 2000).

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of genetic information. To do this, it is necessary to examine the metaphors that are used to describe DNA. DNA may be a large and complex molecule, but alone it does nothing. It does not have powers of self-replication, nor those to create new generations of life. But it is part of a complex developmental system that leads to new individuals. Some of the power of the genocentric metaphors that DNA is genetic information rests on the idea that it is DNA alone that is transmitted between generations. Not so. The egg and sperm are much more than simply vehicles for uniting two sets of chromosomes with their DNA. The gametes contain complex biochemical structures, including the mitochondria and centrioles12 and many molecules (including DNA and RNA), which, given the specific environment of the female reproductive system, can, after fertilization, begin the process of cell division and differentiation that leads to a new individual (a much fuller description of this process is provided by Johnson, 2001b, elsewhere in this volume). The DNA, like the other elements in the system, is necessary to it, but not sufficient. In the system, DNA is not the prime mover. Within the newly fertilized eggs—as in all succeeding generations of cells—the different genes are switched on and off by a changing biochemical system, and different proteins are produced according to which gene systems are activated. At the point of fertilization, it is not simply the sequence of nucleotides of the genes that will play a role in future development. The chemical structures around the DNA may be ‘imprinted’ during the process of egg and sperm production to render a particular gene inactive and, in addition, a vital role is played by the cytoplasm and organelles inherited from the mother. This notion of the egg and sperm being part of the developmental system stands in contrast to the idea of sexual reproduction as a conduit for the transfer of genes between generations. In such a developmental system, information may be seen as ‘a difference that makes a difference’, as Susan Oyama (2000a,b) describes it, using a phrase from Gregory Bateson (1972). Such a difference can be a variation in a DNA sequence or any other element that is part of the developmental system. Thus one meaning of the term genetic information refers to genetic differences that may make for variations in phenotypes. So the mutations associated with the Mendelian diseases, as well as the polymorphisms linked to phenotypic variation— as risk or protective factors in ‘complex’ diseases, body form and appearance and many other human attributes—may be genetic information. Increasingly, such genetic differences can be described in terms of variations in DNA sequences. Insofar as this is possible, genetic information can be provided as sequence information. It is important to note that the concept of making a difference is relative to a particular developing individual living in a particular environment—we are not talking genetic determinism here. Sometimes we can intervene to change the

12 These are independently replicating structures that play an essential part in all cell division throughout life.

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environment so that the genetic disease is not a disease at all, or conversely, so what might otherwise be seen as trivial physiological variation becomes an ‘inherited’ disease. Phenylketonurea (PKU) is an often cited example of the first. This is a recessively inherited Mendelian condition in which affected individuals lack the means to adequately metabolise the amino acid phenylalamine which is common in many foods. Chemicals accumulate in the blood that permanently damage the developing brain. Raising children on a largely phenylalamine free diet avoids the problem (though it has to be said that, like so much in biology, the detailed story is not quite that simple). An example of the second situation is individuals who carry a polymorphism that makes them particularly likely to develop lung cancer if they smoke. If everyone smoked we would regard lung cancer as a genetic disease because those who would or would not get lung cancer would be distinguished by a genetic difference. It is very important to avoid slipping into the misleading habit of talking of genes ‘for’ traits or diseases. There is no gene for Huntington’s disease, rather a mutation which may make a difference, the difference being a process of nervous system degeneration which generally sets in in middle age, but occasionally as early as childhood. Genetic information about sequence differences in DNA is not uniquely derived from DNA. Phenotypic characteristics associated with that difference, as well as the biochemical system involved in the expression of the gene, can serve as potential sources of genetic information, so genetic tests for inherited diseases are not necessarily DNA tests. RNA and the amino acid sequences making a protein can serve as sources of genetic information, as indeed would the diagnosis of Huntington’s disease. Later in this paper I will return to the issue of genetic testing in relation to Mendelian diseases and polymorphisms associated with ‘complex’ diseases. A second kind of genetic information that is of social and political significance is that used to identify an individual—for example, by using a forensic data base— or for assessing the degree of relationship between individuals, as in a paternity test. As already mentioned, this is generally done using the most variable (in terms of nucleotide sequences) parts of the DNA molecules in the chromosomes. These techniques depend on the comparison of sequence information between samples; no genetic inferences are drawn about the DNA sequences examined—any more than would be the case if patterns of fingerprints were being examined. The issue is simply the similarity or otherwise of the DNA sequence patterns. Similarities and differences in DNA sequences can also be used to characterise membership of particular human communities. Frequencies of particular gene variants vary between populations. In some situations this is the result of what geneticists call founder effects. These depend on the particular genetic variants the founders of a community contributed. If, as in the case of Iceland, a population grows from a small number of founders, the population will reflect the genetic variation

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that the founders contributed, plus, of course, any later additions from others who subsequently joined the community. Through sampling, the community can be described in terms of the frequency of particular polymorphisms and gene mutations or, of course, variation elsewhere in their genetic material, including their mitochondrial DNA. Alternatively, an individual’s genome can be characterised and compared with populations of known genetic composition so that a judgement can be made of the likelihood of the individual being drawn from that population. This kind of technique has been used to show, for example, that some gene variants characteristic of African populations which were taken to the USA by slaves are now found in the white USA population, demonstrating the relatively high degree of inter-breeding and how the social categories of black and white do not have direct correspondence with their characteristic genetic variation. As the gene mutations associated with Mendelian diseases are characterised and DNA is used, differences in the frequencies between populations of particular mutations have been demonstrated. So, for example, there is a mutation of the BRCA1 gene which is particularly common in Ashkenazi Jewish populations and accounts for a significant proportion of all the individuals who have a BRCA mutation in these populations.13 Knowledge of such distributions can have implications for health services. For example, if a woman is thought to be at risk of carrying a BRCA1 mutation and is of Ashkenazi descent, she can be first tested for the common Ashkenazi mutation rather than trawling through the several hundred mutations known in the BRCA1 gene. Repeatedly, human history has demonstrated a tendency to see social categories as having a biological basis. We should be aware that, while groups are defined on social terms, in so far as there are characteristic differences in frequencies of genetic variants between ethnic groups, DNA technology can provide a means of describing group membership, at least in a very crude way (see Weijer and Emanuel, 2000). Clearly, one can imagine a number of potentially undesirable ways in which this technology might be employed to attempt to define social groups. The final category of genetic information that must be mentioned is the sequence 13 The discussion has ignored the issue of continuing mutation. Some gene mutations associated with diseases such as BRCA1 are rather stable and many of these mutations are thought to have first arisen long ago in human history and then passed on through descendents. In the case of the mutation associated with Huntington’s disease, it is thought that all those who carry the mutation are the descendants of a single individual in whom the mutation first occurred. There are other Mendelian diseases where there is a continuing relatively high mutation rate, and new changes in nucleotide sequences continue to occur from time to time. For example, it is thought that about half of all cases of Duchenne muscular dystrophy are the result of new mutations arising in the previous generation. Fatal dominant inherited diseases persist in populations either because they do not develop until relatively late in life after reproduction may have taken place or because they have a high mutation rate. Clearly, if a mutation occurred which caused a disease that made it unlikely that an individual who carried it reproduced, the mutation would soon die out. The situation for recessively inherited diseases is rather different. Here carriers who have one copy of the gene with the mutation may be at an advantage in certain situations. So, for instance, carriers for sickle cell conditions of thalassaemia may have a resistance to malaria. However, those with mutations in both copies of the gene may not survive to reproduce. Overall, the advantage for carriers ensures that the gene mutation will be passed to future generations.

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of the genome itself—or, more precisely, the sequence of the composite genome made up from DNA from a number of donors. This is the goal of the Human Genome Project. The genome sequence, now published in first draft, provides a valuable tool to aid the dissection of the molecular processes involved in human development and disease. Much research will directly or indirectly use the published sequence. One approach which will be increasingly employed involves studies in which an individual’s gene variations are compared with their lifestyle and experience of disease. Because individual and environmental variability are so wide, data from very large numbers of individuals is needed to undertake effective studies which can identify associations. Plans are under way in the UK to set up research data bases that might involve half a million or more individuals. Such studies raise several issues including confidentiality, ownership, feedback of information to participants and patenting of information (Martin and Kaye, 2000). 4.

The Social Construction of the Concept of DNA

In the section on genetic information I touched on the conceptual position that DNA has come to occupy in much contemporary biology. Here I will discuss the concept of DNA as a social construction. DNA does have a unique social position as the only biologically important molecule that has a name known in most households in the land. It is perhaps comforting to regard the hyperbole of the socially constructed DNA as simply hype that has accompanied the biologists’ project to sequence the human genome, the associated research in molecular genetics and the commercial applications of these, or, alternatively, as the media misleadingly reporting the work of scientists.14 However, as I have already hinted, the matter runs rather deeper than this, as these conceptualisations of DNA are part and parcel of the metaphors that many biologists use to communicate about their work, among themselves as much as in their dealings with the broader public. The situation is ironic for both a biological and a social reason. As I have already commented, one feature of the socially constructed DNA molecule is the idea that it uniquely represents the essence of our species. However, one of the more significant discoveries of molecular biology is that there are few gene sequences that are unique to our species. Molecular evolution proves to be highly conservative so that many of our gene sequences are shared not only with mice and monkeys but also with bread moulds, fruit flies and the nematode worms in the soil of our gardens. Nineteenthcentury evolutionary theory may have made plain our animal origins, but twentiethcentury molecular biology has demonstrated how close those family links may be, at least at the molecular level. But there is a social irony too. There is little doubt 14 While the media may not always be accurate in their reporting, analysis shows that the spirit of the genocentric and deterministic hype of some of the scientists is faithfully relayed by the media. In this respect the media has effectively served the interests of some scientists (see Nelkin, 1997; Hargreaves and Ferguson, 2000).

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that some of the public’s resistance to new genetic technologies, which may extend to some of the most beneficial and benign applications, arises from a belief that DNA technologies deal in the fundamentals of our humanity—the secret of life. But it is the ways in which some biologists have described molecular genetics that has created this misleading conception of the properties of DNA and so fed the public resistance to and distaste for some of the genetic technologies. Metaphors are a primary mode of communication of ideas within science, just as they are between scientists and the public (Lakoff and Johnson, 1980). Many of the metaphors that are used for DNA and genetic information are both deterministic and essentialist (Keller, 1998; Nijhout, 1990). Often these are drawn from computer or communication technology. The genes or genetic information are described as a computer program or a tape recording. For example, Gilbert (1992), one of the founders of the genome project, in a chapter entitled ‘A vision of the grail’ stated that ‘three billion bases of sequence can be put on a single compact disk (CD) and one will be able to pull a CD out of one’s pocket and say, “Here is a human being, it’s me!” . . . To recognise that we are determined . . . by a finite collection of information that is knowable will change our view of ourselves’ (p. 96).15 Or, as one of the co-discoverers of the structure of the DNA molecule puts it in one of the standard textbooks, ‘we know that the instructions for how the egg develops are written in the linear sequence of the bases along the DNA of the germ cells’ (Watson et al., 1987). Such analogies are unidirectional; information flows only from genes and never to the genes, and so privilege the genes. The genes may be conceptualised in very much the same way as the goods and property that we may inherit from our forebears. There is nothing in such metaphors to represent the flow of information to the genes that controls their function, or to represent the biochemical processes that make possible the production of proteins with particular amino acid sequences, or, more accurately, that information created by the interactions between the genes and the other parts of the developmental system (Keller, 2000). The metaphors are also deterministic in that there is no developmental space between genotype and phenotype. The developmental system and the vagaries of its outcomes are ignored (see, for example, Kurnit, Layton and Matthysse, 1987). Indeed, this determinism is implied when biologists speak of the genes ‘for’ particular characteristics or diseases.16 The implied notion here is 15

That CD is now in the shops (Sept. 2000), a free gift with Prospect magazine. It is important to point out that I am adopting the perspective of molecular genetics here. In classical genetics a gene was a hereditary unit which occupied a particular place (locus) in the genome and which had an association with a particular phenotypic character. So in classical genetics it was perfectly appropriate to speak of a gene for a characteristic. The term was introduced by W. L. Johannsen in 1909 as a shortened form of de Vries’ term pangene. As Mayr (1982) comments, the last thing that Johannsen wanted was to provide a definition of the term gene that was tainted by preformationist language. He warned against those who had ‘a conception of the gene as a material, morphologically characterised structure which is very dangerous for the smooth advance of genetics’. He referred to the gene ‘as a kind of accounting or calculating unit’. As Mayr goes on to say, in due time, the gene has acquired precisely those structural characteristics which Johannsen had been careful to exclude from his definition. But a degree of confusion persisted with some defining genes by a phenotypic character16

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close to that of preformist biology. It is as if the gene contains the trait in some reduced and unexpressed form, much as the minute humanculi that some early microscopists saw crouched in the heads of sperm. These genocentric metaphors are used beyond molecular biology. For example, socio-biology and evolutionary psychology analyse the processes of natural selection in terms of gene selection and perpetuation of certain genes and gene variants in future generations (see the discussion by Bateson in this volume). While the legitimacy of analysis at that level has been questioned (see, for example, Gray, 1992; Godfrey-Smith and Lewontin, 1993), its currency is very wide. It is an approach that makes genes central and places them above all other aspects of the developmental system, and above phenotypic characteristics. A particular influence here on the public has been Richard Dawkins, whose powerful popular writing depends heavily on striking metaphors which often come from computer science and equate the genome with a computer programme (see Lewis, 1999). In this discussion it is important to distinguish a criticism of an over-emphasis on genetic causes from a more general point about the reductionism of molecular biology. The latter strategy has clearly been highly successful. What is at issue is what has been called ‘greedy reductionism’ (Dennett, 1995). As Lewis (1999) has argued, molecular genetics often has the feel of greedy reductionism, trying to explain too much, too fast, under-estimating the complexity and skipping over whole levels of process in the rush to link everything to the foundation of DNA. A small, but illustrative, example here is the calling of the bulk of DNA ‘junk’ because it does not constitute genes. A more substantial one which is particularly characteristic of work on human behaviour are the frequent false claims for discovery of the genes ‘for’ psychiatric conditions such as schizophrenia, which are the product of hasty research with inadequately sized samples and poor ascertainment and phenotypic characterisation (Moldin, 1997; Owen and Cardno, 1999), or the overblown claims of some behavioural geneticists for the inheritance of IQ based on over-simple statistical models and mis-interpretation of heritability estimates (Devlin, Roeder and Daniels, 1997; Daniels, Devlin and Roeder, 1997). Because of the failures of the widely used metaphors to represent adequately istic and others by the locus at which the allele or mutation might be found. In classical molecular genetics a gene is defined as a DNA segment coding for an RNA and/or protein molecule. However, in the classical contemporary era of ‘post modern’ molecular biology one gene can no longer be equated with one enzyme. These are regulatory genes which influence the activity of other genes and split genes composed of coding sequences of DNA (exons) interspersed with non-coding segments. In these split genes the RNA transcript of the gene sequence is ‘edited’ to remove the non-coding segments before protein synthesis can begin. There is also alternative splicing in which different RNA transcripts are produced from a primary transcript. These, and other complications of the process, beg the question of what is a gene: is it the final RNA transcript involved in protein synthesis? In that case, such a gene has none of the permanence of a gene passed down through generations. Perhaps we are back to a classical concept of the gene as a theoretical concept. ‘Genes are not physical objects but are merely concepts that have acquired a great deal of historical baggage over the past decades’ (Gelbart, 1998; see also Keller, 2000; Beurton, Falk and Rheinberger, 2000; Griffiths and Neumann-Held, 1999; Neumann-Held, 2001).

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the developmental process, there have been attempts to develop new ones. The main contender here is the idea of DNA as a language, text or script, with the individual being a particular reading of the text or performance of the script (Pollack, 1994). Such metaphors do seem to provide a way of discussing molecular processes which do not conflict with the reductionism of molecular biology but, at the same time, provide a more adequate model for developmental processes and phenotypic variation. Performances of the same play, even by the same cast with the same producer, can vary widely.17 A biological example is provided by monozygotic twins. Such twins have identical genomes, but they are phenotypically different despite the fact that, in addition to the common genotype, they have shared a uterus and, in most cases, a family and social environment. They have been recorded with different hair colour (Gringras, 1999) and they do not always have the same genetic diseases (Willemsen et al., 2000). In our genocentric world we refer to these people as ‘identical’ twins. Their genotypes may be identical, but not so their bodies, minds or the diseases they may suffer from. 5. Uses of Genetic Information I will now discuss a number of uses of genetic information derived from DNA sequencing in the light of my discussion of genetic material and information. (a) Forensic data bases The idea of a data base of identifying information that could be used to name suspects involved in crime is not new. Traditionally, police have used photographs and fingerprints to do this. Both facial appearance and fingerprints are highly individual phenotypic characteristics which can produce fairly accurate identification. However, fingerprints are not left at all crime scenes and there may not be witnesses who saw the suspect. It is much more likely that tissue containing DNA can be found. And using computer technology, it is also simpler to store and search a DNA data base than a photograph or finger print collection. DNA data bases are already widely used by police (Kimmelman, 2000; Blakey, 2000). Britain has one of the most extensive systems in the world and the law allows the police to collect DNA from suspects for any recordable offence (offences that can lead to certain terms of imprisonment).18 Some senior police officers would like to go further and collect DNA from the whole population.19 Currently, the data base for England and Wales contains 3/4 million samples. In September 2000 it was announced that 17 The story is told of a provincial performance of Waiting for Godot on a Saturday night. Members of the cast were keen to catch the last train back to London for a brief weekend break. They succeeded in knocking half an hour off the usual running time. 18 The UK National DNA Database is operated by the Forensic Science Service, which primarily provides a service to the Police Force, the Crown Prosecution Service, Customs and Excise and other agencies. They also provide a corporate service. A company DNA data base is compiled containing the DNA profiles of personnel and possibly family members to assist in authentication of claims in kidnap and similar situations. 19 Philip Kitcher (1996) also makes this argument.

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further funding would be provided for the police to expand the database so that three million samples from convicted criminals would be on file by 2004, and it is expected that most ‘active criminals’ would have a sample in the data base. Eventually it will cover one third of the male population. The evidence suggests that, at least for serious offences, the majority of the public support the use of forensic data bases (Richards, Rosema and Ponder, 1998), despite the concerns about them that some have expressed. In principle, it would seem that there is no difference between a DNA data base and a collection of fingerprints or photographs. Both raise civil liberty questions about the purposes to which they might be put or, indeed, the accuracy of identification that can be made.20 In Britain some opposition to DNA data bases has come from the police themselves (The Independent, 26th July, 2000). This came to light when attempts were made to collect DNA from officers who attend crime scenes, or handle evidence, so that any contamination by their DNA could be ruled out in investigations. Very few officers have volunteered to give a sample. Their reasons are not entirely clear, but it seems that there had been fears that their sample might be accessed by the Child Support Agency (which has powers to collect DNA to determine the identity of fathers who may be liable to provide financial support for their children) or that samples might be used to gain evidence for disciplinary proceedings. Another line of criticism comes from those who believe that DNA represents the most highly personal and unique information about a person, so therefore should not be held without very good reason. This point arises in connection with a number of uses of DNA. However, it is unclear in what sense DNA is more personal or unique than a photograph or fingerprint, unless the point is argued on the grounds that DNA is part of the substance of the body. But this does not seem to be the point being made here; rather it is the idea drawn from the socially constructed concept of DNA as our human essence. All that would seem to distinguish the use of a DNA data bank from, say, a collection of fingerprints, is that samples of DNA may be easier to collect from an individual’s environment and, given information technology, are easier to analyse and compare with a reference collection. Other differences would arise, however, if the data bank was used in ways other than for identifying samples. The data, or genetic information derived from it, could be used for comparing samples to see whether or not sample pro20 An important additional issue is the extent to which the law and guidelines for the use of forensic databases are followed in practice. The evidence is not encouraging. The Criminal Justice and Public Order Act 1994 requires that if an investigation is discontinued or a person is acquitted the relevant samples and records are removed from the database. Blakey (2000) estimated that more than 50,000 samples are being held illegally because they are not removed as the regulations require. In commenting on this the HM Inspectorate of Constabulary says that ‘in the general interest of crime detection and reduction perhaps the time has come to revisit the legislation to consider whether all . . . samples . . . should be retained . . . to provide a useful source of intelligence to aid future investigations’ (Blakey, 2000, p. 18). (After this was written, the Home Secretary announced in January 2001 that legislation would be introduced to allow just such retention of samples from suspects who are subsequently acquitted.)

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viders were related to each other, or for testing for mutations associated with disease. Neither photographs nor fingerprints could be used for this purpose in any very meaningful way. Another possibility which would be specific to DNA is the suggestion that it would be possible to build a picture of the individual from the DNA; in effect to try to derive a phenotype from the genotype. There are a few body features that could be predicted reasonably accurately from certain polymorphisms. One might be able to predict hair and eye colour, for example, with some degree of accuracy.21 And it might also be possible to make a rough guess at membership of certain populations with particular profiles of polymorphism frequencies. However, the complexities of the developmental processes that link genotype and phenotype are such that it is difficult to see that any profile of much use to the police could be derived. This example illustrates why the metaphor of the genome as a blueprint is misleading. Given human knowledge and action and the appropriate materials, a building can be produced from a blueprint. And this works the other way round. A surveyor can survey a building and produce a blueprint. But we cannot derive the sequences of the genome from an adult body. All we can do is identify the presence of a few particular gene variants that are highly predictive of certain phenotypic characteristics. If an individual develops Huntington’s disease we know that they must carry the mutation associated with that disease. Some eye colours would be similarly predictive. But we could say nothing about the great majority of the genes.22 (b) Relationship testing While DNA testing can determine whether potential first-degree relatives are in fact related with a very high degree of accuracy, it is not the only way in which this can be done. Blood groups have long been used for this purpose, as can other phenotypic characteristics. The value of DNA testing lies in the ease of use of the technique and its accuracy (Department of Health, 2000; Sharp, 2000). A potential difficulty, or advantage, depending on your position, lies in the fact that it is much easier to collect DNA without the person’s knowledge or consent than other kinds of phenotypic information that might be used in this context. This is made plain by an Australian company (associated with Monash University) which offers DNA testing via the web, using hair samples. On their website DNA Solutions state that an advantage of their testing methods is that, not only are these samples easy to collect and transport, but such ‘samples can be taken discreetly, giving you the ability to obtain valuable information, without undue stress or anxiety on [sic] others . . . Thus one parent can DNA test their child, without the consent of the

21 Certainly not complete accuracy. As I have already noted, monozygotic twins have been recorded with different hair colour (Gringras, 1999). 22 As well as the difficulty in principle posed by the indeterminacy of developmental systems, at least at the time of writing we have little idea how many human genes there are. In a sweepstake run by scientists working on the Human Genome Project bets range from less than 30,000 to more than 100,000.

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other parent’ (http://www.dnanow.com). As the company puts it, their approach ‘minimises’ requirements for consent. The utility of DNA testing in this field is likely to mean that it will be used more and more frequently in situations where there is uncertainty about biological parentage or other relationships. Once DNA has been collected it could, of course, be used for other purposes, for example, predictive testing for genetic diseases. That complication and questions of consent aside, the main issue here is the possibility that widespread use of DNA testing to confirm or refute family relationships might reinforce the notion of blood ties as the test and basis of relationship. This might be seen as either predictable or ironic, occurring as it does at a time in which high rates of divorce and separation mean that many children are living with parent figures with whom they have no genetic tie, and in which assisted reproduction techniques are increasingly used to create such relationships. It is of some significance that, in Britain, it is the state rather than private individuals that have made most use of this technology. It is estimated (Rogers, 2000) that about three quarters of all testing to assess family relationships is carried out for the Child Support Agency for determination of obligation to pay for child support or by The Home Office for establishing eligibility for entry to the UK as a family member under immigration legislation. (c) Genetic testing for disease Genetic tests are now available for a large number of the Mendelian (single gene) diseases. Because most Mendelian conditions remain incurable, the main medical assistance available to families is knowledge of the risk of diseases that may run in their families and provision of services for diagnosis (including prenatal diagnosis) and abortion. In many cases, but not all, these tests are based on DNA techniques. These genetic tests include predictive and diagnostic tests for the adultonset dominantly inherited disorders, carrier detection tests for the recessively inherited disorders, and prenatal tests (and in a few cases pre-implantation tests— Harper and Wells, 1999) for both groups of disorders. Uptake of predictive tests are generally modest, with around half of those known to be at risk on the basis of family history opting for tests in the cases of the inherited breast cancer syndromes (BRCA1 and 2) (Richards, 1999) and the non polyposis colorectal cancer syndrome (Lerman et al., 2000) and much less than this for the predictive testing for those at risk of Huntington’s disease (Harper et al., 2000). These low rates of uptake may be explained by a combination of the absence, in most cases, of riskreducing strategies of proven effectiveness, and the late age at which symptoms may first occur. The poor predictive power of the tests for some conditions may also contribute. These predictive tests can also be used as fetal tests, but experience has shown that there is little interest in families in using them in this way. Not only does the use of these tests necessarily reveal that one parent carries the mutation if a fetus tests positive, but there is also a potential issue of a genetic identity between the fetus and one of the parents. Many couples seem to agree with a common view

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of the wider public that prenatal screening and abortion may not be acceptable for adult-onset conditions (Richards, Rosema and Ponder, 1998). The use of carrier detection screening for recessively inherited conditions varies widely between conditions. Where there is high community awareness of the condition and social pressures to conform there may be virtually universal uptake, as for premarital testing for thalassaemia in Cyprus or Tay Sachs screening in some orthodox Jewish communities. In the former case couples found to be carriers almost always proceed to marry but then use prenatal screening and abortion to avoid births of affected children, while in the latter case, where abortion is unacceptable and arranged marriage is practised, matchmakers use the test results to avoid marriages between carriers. These high rates of uptake may be contrasted with the situation in Britain where carrier screening for cystic fibrosis is little used and most couples become aware of their carrier status through the birth of an affected child. The psychosocial and ethical issues raised by this kind of testing have been widely analysed and discussed (see, for example, Marteau and Richards, 1996). A central issue has been questions about disclosure of test results to third parties: other family members, insurance companies and employers. As polymorphisms have been discovered which may be associated with ‘complex’ diseases, the question of offering testing is often raised,23 However, given the very poor predictive power of tests, such as that for the ApoE 4 allele associated with late-onset Alzheimer’s disease (Rubinsztein and Easton, 1999), there is a general view amongst professionals that it is not appropriate to offer such tests (Roses, 1997; Nuffield Council on Bioethics, 1998; Hotzmen and Marteau, 2000). Such tests may sometimes be clinically useful in guiding treatment options for some diseases. Indeed, that may be the case for using ApoE 4 testing in the treatment of coronary heart disease. Interestingly enough in this situation, it is sometimes clinical practice not to describe the test to patients as a genetic test and none of the usual protocols for genetic tests involving pre-test genetic counselling are followed. Part of the reason for this clinical practice is that it avoids the perceptions that ‘DNA’ genetic tests have acquired. There is evidence, for instance, that individuals found to be at risk of heart disease through the use of a DNA test may feel that the development of the disease is inevitable and there is less that can be done about it than where the risk is based on traditional clinical assessments (Senior, Marteau and Weinman, 2000). There seems to be a widespread belief that

23 Despite much optimism about the possibilities of finding polymorphisms associated with common diseases progress in the field has been very slow (see A. Wilkie, this volume). Many claimed associations have not stood the tests of replication. The molecular methods that have been used successfully to identify the genes associated with the rare Mendelian diseases are not proving effective in finding alleles that may be associated with common ‘complex’ diseases. One view is that the wrong search strategies have been employed (Weiss and Terwilliger, 2000; Risch, 2000). But, as Wilkie discusses, it is becoming increasingly evident that the associations with such polymorphisms are most likely to be very weak and so of no use in disease prediction.

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the predictive power of DNA tests will be high simply because DNA technology is involved: another indication of the strength of the cultural image of DNA. Of course, some DNA tests, such as the tests for Huntington’s disease, are highly predictive. In almost all cases, those found to have the mutation will, in time, develop the disease.24 But even among the Mendelian conditions such accuracy of disease prediction is unusual. Conversely, there are many diseases that are better predicted by risk factors and physiological tests that owe nothing to DNA technology. Indeed, the concept of a developmental system would lead to the conclusion that, in most cases, a series of phenotypic characters, rather than a difference in the genome, are more likely to predict disease outcome because there is less developmental ‘distance’ between the disease outcome and the factors being assessed. The other important point to emphasise is that tests for some Mendelian conditions do not use DNA. This is true, for example, for the long established newborn test for phenylketonurea (the Guthrie test using blood from a heel prick) or some carrier detection tests for thalassaemia which use physiological indicators. So what might be different about using DNA tests for carrier and disease prediction and diagnosis? Certainly in many situations such tests are effective and efficient—but not always (Burgess, 2001). For some diseases (such as Huntington’s disease) much more accurate prediction can be offered than is possible by the traditional means of examining family history (children of an affected grandparent will carry a 25% risk and those of an affected parent a 50% risk). As already mentioned, such DNA tests may help to support an image of high accuracy and predictive power derived from societal perceptions of DNA and molecular genetics. Some may see their use as carrying the implication that development of the disease concerned will be inevitable and unavoidable. DNA techniques make possible diagnosis of some Mendelian diseases from a cell removed from an unimplanted (in vitro fertilized) embryo. This technique for selection of embryos for implantation avoids the alternative strategy of prenatal diagnosis which may then involve abortion. However, because of the low pregnancy rates following implantation, and the high cost of the procedure, relatively few preimplantation tests are carried out annually in Britain (Harper and Wells, 1999), though rates are rising. As already stated, most Mendelian conditions remain incurable.25 Functional genomic technology at least holds out the promise of new approaches to analysis of the physiological processes involved in the etiology of these diseases and of a more direct approach to treatment through gene therapy. However, the extensive clinical research carried out of gene therapy has so far led to very little success. The principle behind such work is simple—to replace the mutated form of the gene 24 There is a complication in a small percentage of cases. The mutation consists of a trinucleotide repeating sequence. Most individuals have low numbers of repeats and will not develop the disease. Those with high numbers of repeats almost inevitably develop the disease. However, there is an intermediate number of repeats that may or may not lead to disease development. Test results in this range are a poor predictor. 25 An exception discussed earlier in this chapter is phenylketonurea.

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in the relevant somatic cells with benign alleles—but the practice has proved to be very difficult. Not only must the allele be inserted into the nucleus of the cell (the usual experimental vectors are either viruses or fat droplets) but once in the nucleus the gene must be inserted into the DNA molecule in such a way that the appropriate molecular switches to control the operation of the gene are effective. It all looks very simple in the diagrams in the textbooks but effective clinical procedures have proved much more elusive. A possibility that has often been raised in relation to testing for genetic polymorphs is the idea of technologies which will allow for testing for a very large number of polymorphs simultaneously—so called multiplex testing. By combining tests for a large number of polymorphisms it is suggested that it will be possible to provide useful predictions about many disease susceptibilities and the value to an individual of particular drug treatments and preventive measures (American Medical Association, 1999). While knowledge of some genetic variation may indeed be useful for decisions about drug treatment, the idea of producing a profile of an individual’s disease risks may be very far fetched given the complexity of developmental systems and the multiplicity and unpredictability of developmental pathways. We will discover much more about such systems and, indeed, DNA technologies are clearly providing an approach to such analysis. But the one safe prediction we can make is that the technology for establishing genetic variations in individuals will run far ahead of our understanding of the meaning of such variation for individuals living particular lives in particular situations. But this has not stopped commercial interest in the possibility of multiplex testing. Recently, a start-up biotech company, Genostic Pharma, took out a patent for a gene chip system involving 2,000 polymorphisms claimed to be related to a wide range of diseases and behavioural attributes (Roberts, 2000). But, as many have pointed out, there is little or no evidence which conclusively links most of the polymorphisms and diseases listed, and the predictive power of the genetic tests is likely to be very low. However, in the hothouse world of the biotech start-up companies even the wilder fantasies of science fiction may seem worth a punt. Or perhaps we can see this as another case of a misleading metaphor being taken literally.

6. Conclusions It has become routine for politicians and other commentators when welcoming the latest developments in DNA technology to refer to the new social and ethical challenges that the new technology will bring. However, at least for the existing technologies that have been the subject of this chapter, many of the issues are not new. However, there are seven areas where the issues raised by DNA technology are at least to a degree distinctive.

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6.1. Family Connections While the diagnosis of any serious disease, or the prediction of future major problems, is always likely to have consequences for family members, such consequences are more pervasive and direct and may involve a wider circle of family members, including members yet to be conceived, in the case of an inherited disease. DNA technology, because it has led to predictive and carrier detection tests for an ever growing list of Mendelian disorders, has increasingly raised these issues, though not all genetic tests use this technology. It has not always proved easy to reach consensus about ethical issues related to the disclosure of genetic information to relevant family members (see, for example, Genetic Interest Group, 1998). Traditional systems for the analysis of ethical issues tend to be couched in terms of individuals or society giving little analytic space for concepts of family and genetic relatedness. It has been suggested (Juengst, 1999) that the availability of genetic tests undermines virtues of family life, loyalty, intimacy and security, and threatens commitment to family life, especially for those who live in non-traditional family forms, by focussing on what separates us (genetically) from each other. 6.2. Uses of Genetic Information As I have discussed, information derived from DNA sequences may be used for a variety of purposes. For example, DNA collected for a forensic data base could be used for predictive testing for certain Mendelian disorders, or assessing the degree of relationship between individuals whose DNA is held in the data base. So in the collection of DNA for a particular purpose it is important to ensure not only that those providing the DNA fully understand the purposes for which it will be used and the nature and implications of any information that may be produced, but also that those who hold the DNA do not allow it to be used for any other purpose. The same principle will also apply to collections of tissue from which DNA can be extracted. We already have an instance (in New Zealand) where Guthrie cards containing blood spots collected for phenylketonurea screening have been passed to police for use as a forensic DNA data base without the consent of those whose blood was stored in the collection. Perhaps less contentiously, pathology specimens of tumours from dead patients are used as a source of DNA for testing which can indicate whether or not living members of the family may carry an inherited cancer risk. In some situations where genetic testing is being used to establish risks for Mendelian conditions, it is unavoidable that the tests may occasionally reveal information about the family relatedness of those being tested which may not be known to all those involved. Should such information be quietly ignored by the clinicians or should those being tested be told all the implications of their test results?

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6.3. The Ease of DNA Testing DNA testing can be carried out on very small samples of tissue, including those cell fragments which we all excrete and inadvertently litter throughout our environment. This makes it easy to carry out DNA tests without the knowledge and consent of the person involved. With the growth of DNA technology in a global economy, it is very difficult to see how it will be possible to safeguard individuals from surreptitious use of DNA testing. While some states may be able to impose effective control of DNA testing, there is always likely to be the possibility of off-shore and uncontrolled testing. Already it is not difficult to find overseas companies trading on the web offering testing under conditions that would not be acceptable in the UK.26 As with other technologies, those for sequencing DNA and storing and analysing genetic information become more affordable by the day. 6.4. Reproduction DNA technologies have extended the scope of prenatal diagnosis techniques to a list which potentially could include all Mendelian disorders; and for a shorter list of disorders this will be extended to the testing of embryos before implantation. It is likely that these techniques will be refined further, for example, by using fetal cells recovered from the mother’s blood rather than those obtained more invasively from the fetus. These are techniques for selection of fetuses already conceived, and potentially involve either abortion or discarding of embryos found to carry disorders. However, future technologies may involve modification of embryos. Currently in the UK and elsewhere gene therapy experiments are confined to somatic cell modification, and germline (gametes or cells that may produce gametes) modification is not permitted. Pressures are already growing for research which would cross this boundary, which in any case clearly only exists as a genocentric concept. An example of a potential technique which is likely to receive public support because it will provide a way of avoiding having children with a serious mitochondrial disorder would be the use of donor eggs which have the nucleus removed and replaced with a nucleus from an egg from the mother (Chief Medical Officer’s Expert Group, 2000). Or potentially it might be possible to use a mother’s egg which simply has donated mitochondria added to it. To keep reproduction within the family, mitochondria from the father could be used. This, or techniques that might produce an embryo from two eggs by modifying the genomic imprinting (Johnson, 2001a,b) (so permitting two women to have a baby together), involve modification not of the nuclear genome itself, but rather of other elements of the developmental resources which are transferred in reproduction. In this sense they are part of the germline. Modification of the genome has, of course, been carried out in many plant and

26 An example mentioned earlier is the Australian company offering paternity testing without requiring consent from either the person concerned or parents.

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animal species to create genetically modified organisms for agricultural and research purposes. When genetic modification techniques are available which would permit parents who are carriers of Mendelian diseases such as cystic fibrosis or Huntington’s disease to have children without the risk of passing on the disorder, it is difficult to imagine that they will not be used. 6.5. Social Regulation In the fields of criminal detection, immigration control and regulation of the family, some states have quickly adopted DNA-based technologies which further policies more effectively and efficiently than earlier methods. One imagined vision of the future is provided by the film Gattaca, in which an instant DNA read-out system is used for individual identification in a highly regulated society.27 While the technical capacity to sequence DNA would need to be considerably improved and speeded up to permit the use of DNA as an individual identifier that might be used like an identity card or passport, it is clearly possible that such a system might become technically feasible. Besides the point that DNA in such a system could be used at the same time for other purposes (such as the predictive testing for disease—see point 2 above), and surreptitious testing would be easy (point 3 above), in principle such testing would be no different from the use of photographs or fingerprints. However, DNA technology may well bring gains in effectiveness and efficiency over current systems. 6.6. Social and Ethnic Group Differences Because of founder effects, genetic drift and selection, social and ethnic groups are always likely to differ in the frequencies of particular polymorphisms and mutations in their populations. This is recognised and used, for example, in the targeting of health education programmes related to the thalassemia, sickle conditions and other inherited blood disorders that are particularly common in the Mediterranean, Middle Eastern and African populations which historically have been exposed to malaria, or those related to Tay Sachs disease for those of Jewish Ashkenazi descent. The critical point here is that these groups are defined in social terms by a group identity, not in any sense by the frequencies of gene variants in their populations. However, as, for instance, the history of black-white relationships in the USA demonstrates, where there are conflicts between groups there may be tendencies to interpret group differences in biological terms. The existence of a genocentric culture, and the means of establishing genetic variation at the individual level, opens the possibility of attempting to use allele frequencies to define group differ27 The film does make an important point about new technology—that its effects are not always predictable. The film shows how an individual is able to adopt the DNA identity of another and so evade the system of social control. In real life there are already stories (urban myths?) of house-breakers who leave the DNA of others at their crime scenes. Perhaps we should hesitate if someone asks us to lick an envelope for them. Any government bent on social control would presumably ban self seal envelopes.

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ences in genetic terms. DNA bases could be used to create ‘genetic profiles’ of individuals in terms of alleles. 6.7. Perceptions of DNA A complication which runs through all discussions of technologies based on DNA are the metaphors which are common currency in molecular genetics and in the popular accounts of biological science. Many of these accord DNA with powers and potency which mislead and hinder considered discussions of the social and ethical issues which continued development of the technologies raise. In a situation where there is significant public distrust of the intentions of scientists, genocentric notions of DNA as the essence of humanity and the secret of life inevitably lead to anxieties and concerns about technologies which appear to violate the sanctity of this essence. In order to assess new technologies we need to cultivate an understanding of developmental biology which puts DNA firmly in its place as one of the many molecules that plays a necessary, but not sufficient, role in reproduction and development. Metaphorical DNA is strongly established in scientific and popular culture and undoubtedly it will be very difficult to reduce it to its developmental place. However, in the analysis of social, political and ethical aspects of the use of DNA technology we should strive to distinguish metaphorical and biological DNA. Acknowledgements—I am very grateful to many colleagues and friends who provided comments on earlier drafts of this paper. In particular, I would like to thank Bill Albert, Peter Dicken, Jane Halliday, Martin Johnson, Greg Radick, Sarah Smalley, Sandy Thomas, Tom Wilkie, Ron Zimmern and members of the Cambridge Psychosocial Genetics Group. But, of course, the responsibility for what I have said rests with me and not them. Jill Brown and Sally Roberts provided excellent technical support, as always. J. D. Crowe, Ronnie McCoury, Jean Redpath and Keith Whitley assisted in their unique ways.

References American Medical Association, Council on Ethical and Judicial Affairs (1999) ‘Multiplex Genetic Testing’, Hastings Center Report 28, 15–21. Bateson, G. (1972) Steps to an Ecology of Mind (New York: Ballantine Books). Bateson, W. (1990) Lecture Given to the Royal Horticultural Society, London. 8 May 1900. See Bateson, B. (1928) William Bateson, FRS. Naturalist (Cambridge: Cambridge University Press). Bateson, P. (2001) ‘Design, Development and Decision’, Studies in History and Philosophy of Biological and Biomedical Sciences 32, 635–646. Beurton, P., Falk, R. and Rheinberger, H.-J. (eds) (2000) The Concept of the Gene in Development and Evolution (Cambridge: Cambridge University Press). Blakey, D. (2000) Under the Microscope: Thematic Inspection Report on Scientific and Technical Support (London: H.M. Inspectorate of Constabulary). Burgess, M. (2001) ‘Beyond Consent: Ethical and Social Issues in Genetic Testing’, Nature Reviews. Genetics 2, 147–151. Chief Medical Officer’s Expert Group (2000) Stem Cell Research: Medical Progress with Responsibility (London: Department of Health). Daniels, M., Devlin, B. and Roeder, K. (1997) ‘Of Genes and IQ’, in B. Devlin, S. E. Fienberg, D. P. Resnick and K. Roeder (eds), Intelligence, Genes and Success (New York: Springer Verlag).

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Dennett, D. C. (1995) Darwin’s Dangerous Idea: Evolution and the Meaning of Life (New York: Simon and Schuster). Department of Health (2000) Genetic Paternity Testing Services—Code of Practice (London: Department of Health). Devlin, B., Roeder, K. and Daniels, M. (1997) ‘On the Heritability of IQ’, Nature 388, 468–471. Genetic Interest Group (1998) Confidentiality Guidelines (London: Genetic Interest Group). Gilbert, W. (1992) ‘A Vision of the Grail’, in D. V. Kevles and L. Hood (eds), The Code of Codes: Scientific and Social Issues in the Human Genome Project (Cambridge: Harvard University Press). Gelbart, W. (1998) ‘Databases in Genomic Research’, Science 282, 660. Godfrey-Smith, P. and Lewontin, R. (1993) ‘The Dimensions of Selection’, Philosophy of Science 60, 373–395. Gray, R. (1992) ‘Death of the Gene: Developmental Systems Strike Back’, in P. Griffith (ed.), Trees of Life (Amsterdam: Kluwer Academic). Griffiths, P. E. and Neumann-Held, E. M. (1999) ‘The Many Faces of the Gene’, Bioscience 49, 656–662. Gringras, P. (1999) ‘Identical Differences’, The Lancet 353, 562. Hargreaves, I. and Ferguson, G. (2000) Who’s Misunderstanding Whom? Bridging the Gulf of Understanding Between the Public, the Media and Science (Swindon: Economic and Social Research Council). Harper, J. C. and Wells, D. (1999) ‘Recent Advances and Future Development in PGD’, Prenatal Diagnosis 19, 1193–1199. Harper, P. S., Lim, C. and Craufurd, D., on behalf of the UK Huntington’s Disease Prediction Consortium (2000) ‘Ten Years of Presymptomatic Testing for Huntington’s Disease: The Experience of the UK, Huntington’s Disease Prediction Consortium’, Journal of Medical Genetics 37, 567–71. Holm, S. (1999) ‘There is Nothing Special about Genetic Information’, in L. Thompson and R. Chadwick (eds), Genetic Information (New York: Kluwer Academic/Plenum Publishing). Hotzmen, N. A. and Marteau, T. M. (2000) ‘Will Genetics Revolutionize Medicine?’, New England Journal of Medicine 343, 141–144. Johnson, M. (2001a) ‘Reproduction in the Noughties’, Journal of Anatomy 198, 385–398. Johnson, M. (2001b) ‘The Developmental Basis of Identity’, Studies in History and Philosphy of Biological and Biomedical Sciences 32, 601–617. Johnson, M. (1999) ‘A Biomedical Perspective on Parenthood’, in A. Bainham, S. D. Sclater and M. Richards (eds), What Is a Parent? (Oxford: Hart Publishing). Juengst, E. T. (1999) ‘Genetic Testing and the Moral Dynamics of Family Life’, Public Understanding of Science 8, 193–205. Keller, E. F. (1998) Refiguring Life: Metaphors of Twentieth Century Biology (New York: Columbia University Press). Keller, E. F. (2000) The Century of the Gene (Cambridge, MA: Harvard University Press). Kimmelman, J. (2000) ‘The Promise and Perils of Criminal DNA Data Banking’, Nature Biotechnology 18, 695–696. Kitcher, P. (1996) Lives to Come: The Genetic Revolution and Human Possibilities (New York: Simon and Schuster). Knoppers, B. M., Hirtle, M., Lormeau, S., Laberge, C. M. and Laflamme, M. (1998) ‘The Control of DNA Samples and Information’, Genomics 50, 385–401. Kurnit, D. M., Layton, W. M. and Matthysse, S. (1987) ‘Genetics, Chance and Morphogenesis’, American Journal of Human Genetics 41, 979–995. Lakoff, G. and Johnson, M. (1980) Metaphors We Live By (Chicago: University of Chicago Press). Lerman, C., Hughes, C. and Track, B. J. et al. (2000) ‘Genetic Testing in Families with Hereditary Nonpolyposis Colon Cancer’, Journal of the American Medical Association 281, 1618–1622.

686

Studies in History and Philosophy of Biological and Biomedical Sciences

Lewis, J. (1999) ‘The Performance of a Lifetime: a Metaphor for the Phenotype’, Perspectives in Biology and Medicine 43, 112–127. Marteau, T. and Richards, M. P. M. (eds) (1996) The Troubled Helix—Psychosocial Implications of the New Human Genetics (Cambridge: Cambridge University Press). Martin, P. and Kaye, J. (2000) ‘The Use of Biological Sample Collections and Personal Medical Information in Human Genetic Research’, New Genetics and Society 19, 165– 192. Mayr, E. (1982) The Growth of Biological Thought (Cambridge, MA: Harvard University Press). McEwen, J. E. and Reilly, P. R. (1994) ‘Stored Guthrie Cards as DNA “Banks” ’, American Journal of Human Genetics 55, 196–200. Moldin, S. (1997) ‘The Maddening Hunt for Madness Genes’, Nature Genetics 17, 127–129. Murray, T. H. (1997) ‘Genetic Exceptionalism and “Future Diaries”: Is Genetics Different from other Medical Information?’, in M. A. Rothstein (ed.), Genetic Secrets. Protecting Privacy and Confidentiality in the Genetic Era (New Haven: Yale University Press). Nelkin, D. (1997) Selling Science: How the Press Covers Science and Technology (New York: Freeman). Nelkin, D. (2000) ‘Less Selfish than Sacred? Genes are the Religious, Impulse in Evolutionary Psychology’, in H. Rose and S. Rose (eds), Alas, Poor Darwin (London: Jonathan Cape). Nelkin, D. and Linde, M. S. (1995) The DNA Mystique. The Gene as a Cultural Icon (New York: Freeman). Neumann-Held, E. M. (2001) ‘Let’s Talk about Genes: the Process Molecular Gene Concept and its Context’, in S. Oyama, R. Gray and P. Griffiths (eds), Cycles of Contingency (Cambridge, MA: MIT Press). Nijhout, H. F. (1990) ‘Metaphors and the Role of Genes in Development’, BioEssays 12, 441–445. Nuffield Council on Bioethics (1998) Mental Disorders and Genetics: The Ethical Context (London: Nuffield Council on Bioethics). Owen, M. J. and Cardno, A. G. (1999) ‘Psychiatric Genetics: Progress, Problems and Potential’, Lancet 354 Suppl. 1, S111–S114. Oyama, S. (2000a) Evolution’s Eye. A Systems View of the Biology-Culture Divide (Durham: Duke University Press). Oyama, S. (2000b) The Ontogeny of Information. Developmental Systems and Evolution, 2nd edition (Durham: Duke University Press). Pollack, R. (1994) Signs of Life: The Language and Meaning of DNA (New York: Houghton Mifflin). Richards, M. P. M. (1999) ‘Genetic Counselling for Those with a Family History of Breast or Ovarian Cancer: Current Practice and Ethical Issues’, Acta Oncologica 38, 559–565. Richards, M. P. M., Rosema, M. and Ponder, M. (1998) Unpublished paper, Centre for Family Research, University of Cambridge. Risch, W. J. (2000) ‘Searching for Genetic Determinants in the New Millennium’, Nature 405, 847–856. Roberts, G. W. (2000) Nucleotide Probes Used in Genetic Screens for Determining Genomic Profiles, e.g. for Prognosis or Management (Patent Reference Centre. Derwent Accession Number 2000-097547[08]) http://www.derwent.com/resource/interest/wo097647.html. Rogers, L. (2000) The Sunday Times, 11/6/2000. Roses, A. D. (1997) ‘A Model for Susceptibility Polymorphisms for Complex Diseases: Apolipoprotein E and Alzheimer Disease’, Neurogenetics 1, 101–108. Rubinsztein, D. C. and Easton, D. F. (1999) ‘Apolipoprotein E Genetic Variation and Alzheimer’s Disease’, Dementia and Geriatric Cognitive Disorders 10, 199–209. Senior, V., Marteau, T. and Weinman, J. (2000) ‘Impact of Genetic Testing on Causal Models of Heart Disease and Arthritis: Analogue Studies’, Psychological Health 14, 1077–1088.

How Distinctive is Genetic Information?

687

Sharp, D. (2000) ‘Paternity Testing—Time to Update the Law?’, Family Law, August, 560–3. Watson, J. D., Hopkins, N. H., Roberts, J. W., Seitz, J. A. and Weiner, A. M. (1987) Molecular Biology of the Gene, 3rd edition (Menlo Park, CA: Cummings). Weijer, C. and Emanuel, E. J. (2000) ‘Protecting Communities in Biomedical Research’, Science 289, 1142–1144. Weiss, K. M. and Terwilliger, J. D. (2000) ‘How Many Diseased Does it Take to Map a Gene with SNPs?’, Nature Genetics 26, 151–156. Wertz, D. C. (1999) ‘Archived Specimens: a Platform for Discussion’, Community Genetics 2, 51–60. Wilkie, A. (2001) ‘Genetic Prediction: What Are the Limits?’, Studies in History and Philosophy of Biological and Biomedical Sciences 32, 619–633. Willemsen, R., Olmer, R., Otera, Y. D. and Oostra, B. A. (2000) ‘Twin Sisters, Monozygotic with the Fragile X Mutation, but with a Different Phenotype’, Journal of Medical Genetics 37, 603–604. Zimmern, R. L. (1999) ‘Genetic Testing in a Conceptual Exploration’, Journal of Medical Ethics 25, 151–156.