- Maurizio Salvi, M.D.
Via Nomentana 401, 00162 Roma, ITALY
Approaches of bioethics which interrogate the relationship between ethics and biotechnologies use two methodologies: the scientific approach (1-3) and the theoretical approach (4-6). The scientific approach bases its judgment on the risks/benefits for equilibrium of the biosphere. The second approach tends to extend analysis to more generic themes such as:
- Responsibility toward future generations (7);
- Respect for animal rights (5, 8, 9);
- Research of an universal utility for humans (10, 11);
- The relationship between ethics and society (6).
The scientific approach which remains linked at the level of biological problems, allows us to clarify what dangers biotechnology causes for the living world. But is this enough to define it as bioethical analysis? The word bioethics links two apparently separated dimensions: biological (or medical) phenomenon and ethical analysis. Considering only the first dimension, the judgement which follows leads basically to a prudential attitude toward advanced biotechnologies; meaning that risks of a biotechnological application will be reduced at the maximum in order to increase benefits that it expects to obtain. But this does not mean that an ethical judgement has been expressed.
The first effort in an ethical analysis is that of defining epistemological coordinates on which to build ethical theory. By epistemological coordinates I mean the definition of criteria (or notions) to found - or justify - choices and prescriptive judgements. We could value the applications of genetics and put in evidence what this would mean for the equilibrium of the biosphere, or for future generations. Knowing the type of questions we ask ourselves when we search for what is good or what needs to be done in a certain situation. It is preliminary, a logical and conceptual point of view, to express our judgements. Through which criteria do we approve or condemn a biotechnological application? What is the ethical value of DNA? Is it an instrumental or intrinsic value? And how do we value manipulations of DNA in terms of ethical value?
The transformation of scientific judgement (risks / benefits/ responsibilities) on the ethical level is neither a natural or obligatory passage. In the first place it involves analysis of the ethical meaning (not only scientific) of biotechnologies. If such an operation is not perceived, bioethical analysis of risks divide the pragmatic level (science) from the theoretical level (philosophy). The philosophy should analyse the ethical meaning of biology in its concrete reality. In the same way science should understand that its own judgement can not be considered a judgement of value if it does not question itself on what has to be considered ethically correct (1). What I would like to underline is that bioethics was born as a sincretic dimension. Within it there are several disciplines which value particular phenomena from different perspectives or points of view. If an epistemic hierarchy is defined for them (first science, then law, philosophy and sociology, for example), the objectivity of bioethical analysis will be compromised. The possibility to enrich bioethical studies with the instruments of the disciplines involved will become less. Bioethics is a "polyphonic" science. It is an "ensemble" of voices (scientific disciplines) which find opposition or are placed one upon another, but they are all part of a unique chorus. This is the peculiarity of a discipline so complex but also so fascinating.
2. What value can be attributed to DNA?
I propose a scheme for a possible interpretation of the ethical dimensions of DNA. The schematic nature is dictated by the impossibility to analyse in a complete way the peculiarities of our object (for reason of space). Let's consider the genome as an identity. The concept of identity responds to a double logical dynamic:
1) I define something in terms describing its requirements within a determined time period;
2) I can recognise it in different temporal coordinates because it has characteristics which will lead me to define its own identity as a continuous identity over time.
These two dynamics respond to two peculiar themes of personal identity: definition of identity in terms of significant requirements for the observer, and its own continuation. Using the language of R. Nozick in Philosophical Explanations (12), we will talk in the first case of transverse entification, and in the second case of longitudinal entification. The purpose of this article is that of building up an ethical theory of biotechnology, through logical dynamics of analytical philosophy, applied to problems of personal identity. Therefore, our reference points are works of T. Moore (13), R. Nozick (12) and D. Parfit (7). But the work of Nozick is of particular importance, both for his theory of the closest continuer and theory of intrinsic value. Certainly, the American philosopher did not focus his complete attention on bioethical problematics; this does not mean that his own considerations can not constitute a different key of interpretation for biotechnological problems. The entification processes of genetic identity of a single human being are determined through those two logical processes which are strictly interrelated: transverse and longitudinal entification.
With the term transverse entification (TE) we signify:
1) The chemical-physical definition of the genotype of an organism (nucleus structure);
2) Its stereochemical structure.
With longitudinal entification(LE), we indicate the element of continuity through which the identity of the organism remains identical to itself over time. LE incorporates both the geneotypical dimension of X and its own phenotypical translation - in other terms the relation of the x-genome within individual X. From an ethical point of view such dynamics refers to:
1) processes of homeostatic regulation;
2) processes of phenotypical translation of DNA;
3) mechanisms of regulation of physiological functions of the organism in itself;
4) meiotic processes and transmission of progeny.
The TE - the chemical nature of DNA - necessarily entails the longitudinal one, because DNA organises and regulates the phenotypical development of X. Talking of development means identifying a third variable within the logical dynamics which links X entification: time. The same nature of the biological organism (for example, continuous substitution of its cellular components) includes in the definition of the identity of X, its temporal extension. The same consideration may be extended to DNA. The genetic heritage is the container of information which regulate the homeostatic functions of an organism. At the same time, the DNA contains information for the enzymatic synthesis of the organism. Time is strictly ingrained to the genetic definition of the organism in its three fundamental coordinates of DNA:
1) The present of TE of X - I define the stereochemical dimension of X in the time of observation;
2) The future of LE - information contained in the x-genome will regulate the biological functions during existence of organism X;
3) The past of both - the genotype is the result of maybe 4 billion years of genetic information.
If we move from the level of genetic identity of the individual in his singularity to that of population genetics, then it follows that DNA is not only historically determined in its singularity (stereochemical), but also in multiple unity of the genetic population pool (as an individual that belongs to a species). The individual is a determined unity but at the same time he belongs to a species and he is the result of biological evolution directed at the future - we could refer to the consideration on molecular evolution of M. Kimura (14), M. Eigen (15), J.Monod (16). Let's now analyse the relationship among temporal coordinates of the DNA. Can we attribute to one of them a predominant value?
If we define (for our hypothesis) that DNA has to be safeguarded because it contains genetic information accumulated during biological evolution, we should automatically condemn genetic therapies. The impossibility to control the retrovirus in the phase of DNA transformation can cause insertion in the region of the non-coding-DNA. Since we don't know exactly which function is carried out by this region of the genome (the so-called "junk" DNA constitutes about 95% of the human genetic heritage), an alteration could be conceived as a destruction of the information accumulated in the biological past of the organism in question. If the temporal dimension of the past is considered biologically more important, then the risks of gene therapy would automatically lead to a condemnation of such biotechnological action. On the contrary, if we regard the present existence of X to be a superior value, the judgement will be over-turned. The pathological mutation would be corrected in order to re-establish the nucleus structure of subject X. Do we then attribute a value to the future nucleus, as a dimension that needs to be safe-guarded? We have said that the present genetic identity of X is its own genotype. If we operate in this dimension some genetic manipulations (we could think of positive eugenic or somatic applications), our action is reflected on individual X but not on his descendants (therefore not on the genetic population or on future generations).
On the contrary, if we interact with germ cells, we will create possible repercussions not only for present X, but also in his future. The repercussions will interest X as a singular individual (his genetic identity would be deeply marked), and as a member of the biological population (the manipulation would be transmitted to his descendants, and therefore to the genetic pool of the species). At the same time this operation will determine repercussions also in the past dimension of X's DNA, because it will modify a nucleus structure that accumulates data (in a chemical form) from billion years. Going beyond any prudential attitude(2) strictly linked at the scientific discussion, the bioethical analysis necessitates clarification of the ethical coordinates at the basis of our bioethical theory.
3. The DNA as a dimension to be safeguarded
We are back again to the fatidical question: what is the ethical basis to approach biotechnological problems? My opinion is that this fundamental element has to be researched in DNA. The DNA has to be considered like the dimension of value through which applications (or experiments) of applied genetics have to be judged. The DNA is not an instrumental value, but a constitutive - intrinsic - value in a minimal sense. It has constitutive value because DNA is the fundamental element of life. Since all living forms have this element in common (only its level of structural complexity varies) I believe that it can not be defined other than as a dimension of value. A dimension that must be safeguarded. The level of value of DNA is related to its temporal coordinates. The present genotype of an organism absorbs both the past of biological evolution, and -mainly - their future. It is this last dimension which has a fundamental primacy in terms of value. Applied genetics that violates such dimensions becomes a disvalue. DNA is the fundamental principle of causality that bounds the entification of the X's genetic identity -w hether LE or TE. As such, it must be safeguarded (3). Because, if we consider the genotype as a dimension of value, we can derive that each biotechnological application can be ethically valued in terms of the safeguarding of the dynamics through which individual X is an identity (4). We have defined DNA as a minimal ethical dimension because, if we think about DNA's ethical value as an absolute value (in metaphysical and ontological sense) the risk is to condemn all biotechnological applications which create genetic manipulation. As a consequence possible positive applications (e.g. gene therapies) would be automatically disvalued. In reality, is the minimal value that we attribute at the DNA, which allows some biotechnological applications?
We can now think of somatic cell gene therapy. In such a case therapeutic action relates to the dimension of the present X. The manipulation of the genome is applied as a therapeutic function without touching the genetic identity of subject X. But if we think of germ-line gene therapy, then our judgement varies. Here the genetic identity in itself of subject X would be touched. In fact, our action does not relate only to present x-DNA, but covers also its future dimension. This happens at two levels:
1) The genetic identity of X is changed in X'. As a consequence, phenotypical translation of X' genotype will be different from that of X;
2) The individual will transmit their new genetic identity X' to progeny. The manipulation will be then transferred to the population genetic dynamics of future X.
To violate the temporal entification of X in its future coordinates (5) (both as a biological identity and as a member of a population), means not respecting the dynamics through which the identity of X is constituted and preserved over time. In the same way it means violating transmission - by means of reproduction - of the same x-identity in history (to descendants). These considerations could be extended to any intervention on germ-line cells.
The consciousness of this issue should be extended to the scientific community and to all those institutions involved with policies for scientific research, because bioethics belongs to, and should involves in the first place, the people. Certainly, this theory can be questioned if the genetic identity of an organism is not considered as a value to be safeguarded. The analysis of personal identity achieved by analytical philosophers give us significant instruments of analysis for problems regarding the identity of the subject that undergo germinal gene therapy or cloning. Themes of the analytical philosophy give us an answer regarding some problems of bioethics. For example:
1) "Do themes like self identity vary with the changing of his parts"? We could think of cell substitutions in the organism, or of transplantations;
2) "Should the identity be considered as a gathering of elements or as an identity in itself?" Thinking of the pre-embryo: is it a biological liquid or a potential individual?;
3) "Is the identity a biunequivocal property such as X=X, or may we allow elements identical between them (X=Y=Z=)"? We could think of cloning or identical twins.
What I am trying to underline is that when we focus attention on the formulation of an ethical judgement of biotechnological applications that we are analysing, we can proceed in two distinctive ways:
1) Attributing motivations (and aims) to such actions, the primary term (and ethical valence) of our judgement;
2) Trying to value the ethical dimension of our actions for how they determine the subject (X) which undergoes them.
Since the criteria of judgement have always been external to subject X -we could think of the solution of contractualism or utilitarianism- why not build up a theory that interrogates consequences of the therapeutic action on the identity of the subject? Of course, this is an operation internal to the subject, and it can easily find opposition when the basic premise is not accepted - that is the identity of X is to be changed, but this does not undo our effort. On the contrary, this obliges us to a commitment for internal justification of our philosophical applications, and to a choice over the instruments through which we judge whether an application of biotechnology is ethical.
I hope that this article has shown how biotechnological problems could be approached with a different logic. A possible analysis of DNA value has been suggested, and we should welcome research on other routes to answer the problems that biotechnology offers to us.
1) We could think of applied genetics. If we identify our ethical hinge in respect of natural laws, profound implications will arise. We bring an object to judge (biotechnology) on a level intrinsically extraneous to it. Applied genetics, as human possibility to manipulate or interfere with the structure of life, is already a process that goes beyond natural laws. As a consequence, the possibility that a biotechnological application will be considered in terms of disvalue (being contrary to our primary ethical coordinates). Our analysis should therefore define which type of value is attributed to natural laws: an intrinsic value, and in this case medicine would be described in terms of disvalue, an instrumental value, biotechnology would automatically acquire a positive ethical value in function of this respect for the fundamental laws of nature. On the contrary therapeutic applications of gene therapy would result in an artificial correction of a natural process (pathology as a teleonomic symptom of biological censure for those genetic paths useless to evolution). A Reflex value -the scientific community and society would establish a value for genetic applications (but who should decide? In function of what? Economic interests, quality of life?). The problems are extremely complex.
2) We could refer to epidemiological risks and repercussions on the evolutionary directions and dynamics (M. Ridley 1985). For example the problem of synonymous sequences.
3) A question may arise: What ethical value do germ-line or somatic cell gene therapy acquire? Considering the x-genome as a dimension of value, somatic cell therapy would merely be a restructuring of a structural alteration of X, able to restore the correct translation of X in x-phenotype, and therefore restore health in the patient. Instead for germ-line therapy the therapeutic operation would determine an intrinsic modification of the x-identity in his future temporal coordinates, and would be reflected on the population's developmental dynamics to whom X belongs. As such, it would be appraised in terms of disvalue.
4) In the present of the x-individual, in the past of his structure of data (chemical-physical), in the future of the transmission of the x-identity in the biological population composed by x-components.
5) At the light of our considerations, we could introduce a relationship (in terms of ethical value) among the temporal coordinates of DNA : future > present > past. In reality things are more complex. The LE (to whom the present and future of the x-identity has to be reconsidered) is strictly linked to TE (present and past). The phenotype translates the genome, but finds in it information required for such operation. In reality a complete separation between present - past- future does not exist within the DNA. The three coordinates are intrinsically linked in a way that each one follows the other. We have underlined the importance to preserve the future dimension of DNA, because it is directly at the relationship between the x-subject and the species to whom he belongs. If a person wants to submit itself voluntary to radiation, he is free to do it. But if such radiations cause pathological mutations on his germ cells, then the pathology can be transmitted to the progeny (in the respect of the laws of inheritance of characters). In this sense, the future of the DNA becomes ethically more significant for biotechnological problems.
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