pp. 278-283 in Bioethics in Asia

Editors: Norio Fujiki and Darryl R. J. Macer, Ph.D.
Eubios Ethics Institute

Copyright 2000, Eubios Ethics Institute All commercial rights reserved. This publication may be reproduced for limited educational or academic use, however please enquire with the author.
8.4. Human Genetics and the Integrity of Self: Germline Gene Therapy and Cloning

Maurizio Salvi,.

Maastricht University, Netherlands

The purpose of this paper is to analyse the ethical meaning of Germline therapy (GLT). I will defend an ethical analysis by linking self identity problems to the genetic manipulations. I intend to address the problem of how the violation of the genetic identity of the individual could involve the destruction of his/her natural identity and the replacement of the latter with an artificial one.

The reasons that have led me to choose this unusual instrument of bioethical analysis can be simply explained: in the biotechnological applications on germ cells of an organism, a transformation of his self identity is made. This means that the organism is subject to external actions that he may have not chosen (in the cases of therapeutic applications we think that he approves the therapy as re-establishment self health, but nothing allows us to know that this would have been his choice), and that Germline therapy causes genetic changes in its identity. A biotechnological application on an organism is, thus, the result of the subjectfs external purpose, with consequences on his identity.

The scientific literature has analysed the first point, considering the ethical meaning of applied genetics to depend on the risks-benefits (or purposes) of these manipulations. However, in the specialised literature ethical analysis studying the meaning of the organism specific identity transformation using an analytic approach is quite absent. But, since a bioengineered organism (as a future subject) has no freedom of self determination, the transformation of his genetic identity must be, at least, considered problematic.

In an analysis of the consequences of a genetic transformation in germ cells with regards to the self-identity problems. We need to clarify:

1. What the identity is?

 The question is: why do not we utilise the theories of those others philosophers who analysed the identity-problems: Williams, Parfit, Nagel? Let us look at these theories with reference to our study object: the pre-embryo. The key with which Nagel analyses a subjectfs self identity is the brain identity. Nagel thinks that the existence of Self is related to the existence of his brain, and the continuity of SI in time is related to the physical continuity of the brain. Identity consists of onefs Psychological Identity and also the continuative existence of the brain. This philosophical key can be utilised as a really clear condition for the identity of superior organisms which have a central nervous system. But the pre-embryo is a phase of biological development where the cells are not yet differentiated into tissues or organs. Therefore, no brain and no Psychological Identity! The requirements of the Xfs identity have to be searched in some other theory.

Williams think of self identity as a corporal identity. At the same time he considers corporal continuity as a fundamental criterion of self identity and of his continuity in time. Williams intends self identity to be a biunivocal relationship (X=X). The relationship which ties the identity in time is an equational one. But if we think of an individual X as a biological organism we cannot ignore the problem of Xfs cellular components substitution. The cell components which constitute the corporal identity increase numerically. This means that X cannot be analysed as an identity X=X, since in different temporal phases Xfs identity will be constituted by a different number of sub-elements (the cells). Moreover if we try to apply the Williamsf criterion as the clarifying key for the pre-embryo entification, we will not have instruments to understand the problems involved in a qualitative transformation of organismfs genetic identity. In fact, although we operate some transformations on the DNA cellular components forming the pre-embryo, nonetheless the embryo completes his biological development, translating phenotypically the transformed DNA. Corporal identity will be safeguarded! We still have to clarify if another requirement of X could be utilised as an exhaustive instrument to solve our problems: Psychological Identity.

Parfit thinks that self identity fundamental criterion must be completely changed: identity is not limited to determined elements. To talking about self in these terms does not mean to indicate only one of the requirements which constitute the Identity is a dynamic relationship whose requirements change in time. The fundamental element of identity is not to be researched in the selffs requirements. Our choice is an hypothetical research of a requirement definition that cannot justify what really is important regarding SI problems. Because Parfit thinks that SI is not important, or better, that it is not the fundamental element of Self. This element must be searched for in the relationship R, the psychological connection and/or the continuity with the right type of cause (every cause can be the right cause). The fundamental element for the continuation of a subject (X) in some other (Y) -or in himself- is not the identity of the same subject, but the relationship R which links X and Y.

Lets consider the X pre-embryo: where we need to analyse his identity in function of Parfitfs theory, we would need to prove that psychological connection cannot be considered a clarifying key for pre-embryo problems. In addition, if we think of the consciousness formation, which begins after the pre-embryo phase, we do not have a clear reference on this consciousness. Formation of the nervous system begins after the 40th day of embryo development. We do not know if embryo feels pain (like we feel pain in a complex nervous system), nor do we not know if he has memories. We can assume that embryo has a consciousness unity, but we do not have elements to judge if our hypothesis is correct. This theory of maximum similarity relationship during the development phases of embryo cannot solve the problems of genetic identity transformation; it can be discussed advancing the same objections made to Williamsf theory. We can synthesise the philosophical debate on identity as follow:

Philosophy and Identity-Problems
1. Brain Identity (Nagel -1973-): Self identity consists of the cohabitation of our Psychological Identity and also in the continued physical presence of the brain
Criticisms: If we limit the identity of an organism to the posses and continuity of a conditional requirement (the brain), when this element is absent (the an-encephalic children for example or an amoeba), we donft have rational tools for understanding the nature and the meaning of a biological identity.
2. Corporal Identity (Williams -1973-): We are a body and this body will persist in time by continuing our existence - biunivocal relationship (X=X)-
Criticisms: We can not use the equational dynamics in biological identities because in different temporal life phases, an organism will be constituted by a different number of sub-elements (the cells), and it will have continuous structural changes in its physiology.
3. Psychological Identity (Parfit -1984-): The Identity is not important. We have to consider the identity as a dynamic system which continuously enriches itself by maintaining a set of causal properties ensuring the unitary meaning of an organism in its psychological continuity in time
Criticisms: If we consider cases where the central nervous system is not yet formed (pre-embryo) or animal forms which donft have a sufficient degree of development to talk about a psychological identity, we donft have explanatory tools to understand their identity
The basic problems is: if we think of human identity in a pragmatic perspective we have to think of organismfs identity in its own biological peculiarities-requirements. And our analysis need to be coherently extended to all the organismfs life-stages: from the Embryo to the rational agent.

Philosophical views used a really theoretical approach on this topic. This methodological approach often causes the impossibility to use them in practical cases of identity. This phenomenon is particularly clear, when we applied philosophical views to the biological properties of human beings. In the table (Philosophy and Identity-Problems) I have pointed out the reasons inducing me to refuse some philosophical paradigms on identity. My criticism are based on the impossibility to use these views as exhaustive explanatory models in biological identities. The question is: How can we define the human individuality?

In my analysis I will use a really specific identity view: the organism as an Organic Unity. The concept of Organic Unity (and its use of organismic biology) defines the organism as a com-presence of an heterogeneous and cohesive biological complexity.

Properties of the Organic Unity gOrganismh

Structural properties

Qualitative properties
@

@

Inner Causality		 Cells are clones of an unique cellular line. Every level of the integrated complexity gorganismh is causally linked to the other. In an gorganismh: each level of complexity is compounded into new entities at the next higher level of complexity. The coexistence of systems and their cohesive integration, causes the gemergencyh of characters which canft be deduced by the knowledge of organismfs constituents.
Inner Similarity Cells have a commune DNA and a structural (variable) similarity. Organisms components have similar physiological mechanisms producing different results.
Homeostatic Function The organismfs life is the result of a structural interconnection within different biological systems, The organismfs life is based on its homeostatic structure and adapts its inner-variability-in-the stability to environmental pressures.
Unitary Entity The organism is a cohesive dimension of heterogeneous constituents, sharing a space time system and forming an unitary locus of structural integrated complexity The organism is an unitary homeostatic entity which links itself to environment and maintains a continuity in its own.
The organism is formed by constituent sub-units (cells, tissues, organs); it is the shared space these requirements have all together. At the same time, it is an unitary entity because the coexistence of its heterogeneous and integrated constituents defines its identity in its own, and its continuity, independently to its composite and variable nature. The identity of an organism, thus, is a locus of integrated units/diversities. It is not limited to some particular requirements of an organism but it is an unitary dimension. The properties of organic systems can be defined in their nature of wholes (homogeneous entity) and in the impossibility to deduce their peculiarities (at each level of complexity) in the knowledge of one (or the sum of) level(s) of the biological complexity of their own constituents. The unitary meaning of the unified complexity of a biological system, thus, becomes the a possibility to understand the emergent properties of the whole in its unity/complexity. For an organism we can classify the biological components which form it into sets (organs -> tissues-> cells-> proteins-> genes ....). The causal relationship within organismfs constituents (in any level of complexity of the hierarchical structures) is linked to the biological property: gthe entities at one level are computed into new entities at next higher levelh. Entities of a hierarchy level are related to constitute a second superior level following a dynamic that terminates with a super-unity absorbing in itself all sub-units. This resulting unity is the result of a unity/diversity of components, it is a Organic Unity.

Accepting the Organic Unity View means to deny reductionistic biological paradigms in biological identity, such us: exhausting the organism identity of a subject in his/her genetic identity (either in a individual specific level or species specific level). The concept of Organic Unity is linked to two properties linking the biological sub-elements forming the organism: 1) the maximum similarity; 2) the internal causality. These properties ensure the unitary meaning of an organism and its continuity in time.

2. Pre-Embryofs identity

 Since we are interrogating ourselves on the consequences of germline therapy on organism identity we have to solve this specific problem: Is the Embryo -in his first embryogenetic stages- an gidentityh or simply a cellular whole? The application of organic unity theory to organism identity is linked to the respect of two condition: maximum similarity within organism sub-units; inter-causality within organismfs sub-units. Let us find out if these condition are respected in Pre-Embryo.

The fundamental characteristic of the pre-embryo is that it is a class of similar elements (totipotent cells) that increases progressively. The relationship tying the Embryo-components is not only a space-time relationship (all the cells together in a same space and time). It ties in a causal relationship with the cellular components of Embryo. The blastocysts are clones of egg cell fertilised and increase in time. First causality in blastocysts is the fact that they are clones of the same cell, and they cause the existence of others Embryo-components. The pre-embryo components are units which have in genetic information the internal causal principle working for a common purpose: forming the organism. This demonstrates that pre-embryo , is not a whole of cells tied by chemical relations, or by space relation, but is an unicum which is evolving: it is an identity.

The fundamental link inside blastocysts is the genetic code contained in themselves. DNA is the element (grequirementh) consenting us to evidence the internal causal relationship among the cells, and the gunitaryh meaning of embryo.

The genome is the principle assuring the continuos direction of temporal evolution of the pre-embryo cells whole.

 This means that the transformation made on the pre-embryos genetic identity is transmitted in the same global mechanism of his entification, because genome contains the chemical information regulating the homeostatic work of embryo-cells, and the causal relationship of cellular sub-elements which constitute the embryo-identity. Transforming embryo genetic code causes a bifurcation inside his biological identity.

3. Ethics.

 While the possibility to think of embryo as an identity is clear, the philosophical step leading from identity to its moral Value is not.

I will use a really specific moral parameter: the intrinsic value. The notion of Intrinsic Value that I wish to utilise does not have a metaphysical or ontological meaning. Intrinsic Value (Nozick 1981) as an axiomatic explained value. If we think of living beings, we can suppose the existence of a minimal basis of meaning in themselves. This minimal parameter is based on the phenomenological nature of living beings: they exist, they are percepted, they have a value in se. But this is the minimal condition of all living beings.

The growth of biological complexity is strictly extended to the global meaning of an organism: the complexity rate of an organism increases its value (this mean for example that the value of a pre-embryo is not identical to the value of a foetus, and the value of a cat is not identical to the value of a stone). In human beings, the mechanism of growth of complexity of an individual is reinforced by his rational properties (or mental states), because the biological complexity is enriched by the psychological one (self-awareness mechanisms etc.).

If we stress the human biological properties it follows that the process that unifies Self in self-awareness dynamics accompanies the self unification as biological organism. The relationship which links these dynamics is an analogic one. As the I unifies itself in the Self, in the same way its body unifies itself as Organic Unity.

In Embryogenesis DNA gives the organism genetic material for selffs entification. As the Self unifies with I increasing in time his Organic Unity, in the same way the DNA unifies and regulates the entification of the organism, as unity-diversity.

DNA, thus, is not the basic and exhaustive element of organic systems, but it has a causal role in human entification. The analogy between DNA and rational activity is merely based on their functions: to unify the heterogeneous diversity gthe organismh in an unitary entity. But the same composite nature of an organism denies the possibility to attribute a basic value to genotype with regards the other constituents of living beings. The life in a synergy of numberless factors: biology, environment, culture, psychology etc.

Self and the genome, therefore, made an analogic function in organismfs identity.

 4. Germline therapy (GLT)

 Germline therapy allows correction of gene anomaly, and insertion of transformed gene in to germs cells (eggs and sperm) or into cells of a pre-embryo. I will analyse the technique using viral vectors because it opens the possibility of performing genetic engineered on a large scale.

The fundamental difficulty that Germline therapy needs to resolve, is not the nucleus sequences transformation, but planting the correct gene in right gene locus. Retroviruses are instrument with which the corrected gene is planted, but this is made with little possibility of controlling the position that this sequence will have in nuclear structure.

When we think that we know the function of only exons -5% of the genome-, and that human genome contains 3 billion bases, the chance nature of GLT is clear. We have an opposition of two principles:

the hazardous nature of the Germline therapy,

the causal role DNA in organism specific identity in Pre-Embryo.

Modifying the genetic structure of a subject means damaging the dynamic of subjectf self entification: the phenotype translation of genotype. Changing this dimension means fixing a bifurcation in the organism-identity. Germline therapy, thus, breaks the natural relation of pre-embryo development progression.

If Embryo has a progressive minimal Intrinsic Value in itself (a value increases in time, depending on his Organic Unity degree of complexity) a germline therapy has a strong moral implication because interacts with the mechanism of entification of the organism.

This means that Germline therapy interacts with the entification process of the subject that undergoes this biotechnological application. Germline therapy does not change only the Organic Unity gorganismh, but also one principle of its fundamental internal causality: the phenotype translation of his genotype. The genotypic causality is substituted with the Germline therapy chance nature.

Conclusions

 When we transform a genetic identity we interact with the causal role of DNA. The heuristic level of human genetics does not allow complete control of bio-engineered nucleus sequence plant. In this sense, the causal role of the individual-specific genetic identity is substituted by a gfortuitoush mechanism of genetic transformation. The individual-specific identity is transformed, and we break the natural relation of embryo development progression.

In parallel, because the organic unity gindividualh has an intrinsic value of its own (a minimal constitutive moral status), the interaction with the causal mechanism of embryo development individuates a moral implication: we create a bifurcation inside the individual-specific identity of an organism. The moral implications of a germ-line-gene transformation, thus, become really problematic because the embryo transformation will be extended to the individual specific global entification (and will be inherited by the progeny).

It is clear that this analysis on Germline therapy does not aim at exhausting the moral implications of this human genetics technique. It simply aims at defying the consequence of this act with regard the identity of an organism. And it is not based on the ethical translation of genetic reductionism (which attributes to DNA a basic and exhaustive value in organic systems)

I donft think we have reasons to accept the reductionistic genetic paradigm (jumping gene, synonymous sequences, and the genetic replies to environmental stress in heucariotes are other examples of this structural variability in DNA). The same concept of Organic unity denies this possibility; but since we are manipulating germ cells we need to emphasise the role of DNA in this embryogenetic step (or we risk to follow a theoretical approach to the involved problem which canft clarify the properties-peculiarities of an human being in his embryogenetic stage). In this sense I stressed the value of DNA in personal identity and the consequence of its manipulation in human genetics.

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