How to Calculate the Utility of Human Germline Gene Transformations? A critique of Utilitarianism

- Maurizio Salvi, Ph.D.
Research Fellow, Maastricht University,
WTMC Institute, Dept. of Philosophy,
P.O. Box 616, 6200 MD, Maastricht, Netherlands,
(Email: M.Salvi@Philosophy.rulimburg.nl) Eubios Journal of Asian and International Bioethics 7 (1997), 36-38.


Premises

A really hard question for the utilitarianism approach in Bioethics is linked to the choice of the right tools for evaluating the relationship between the utility of an act and its consequence (1, 12, 18). Let's consider the problems that Utilitarianism has to solve for building a coherent analysis of the moral dilemma linked to human genetics (HG). I focus my paper on the therapeutic application of HG (germline gene therapy GLGT) because this is the most reasonable biotechnological application on human beings. I consider GLGT as a "reasonable" application of HG because has a precise finality: the treatment (16). If we hypothesise some HG applications to cultivate (or improve) some particular human peculiarity -let's think of nazi eugenics-, we have a whole of problematical implications which need a moral analysis (2, 9).

In fact if we think about the eugenics, the scientific community is quite agreeable to defining many fundamental problems which cannot be clarified (8), and which push the biologists to give up on eugenic applications of HG (e.g. how to choose which genetic character to improve? Why affect the right of self-determination of future subjects - I use the concept of "self-determination" as human right to maintain our own genetic identity. First "self-determination" of an organism is the phenotypic expression of its genetic identity (21, 23).-?); But when we are considering the therapeutic applications of HG, it is not easy to define all the reasons which can bring the biological community to refuse HG applications for example treating cancer or for improving the immunology factors in future generations (let's think about HIV) (29, 30). In this sense, if we want to maintain a neutral approach to Bioethics (Sidgwick at 1874 shown us the importance of the neutral approach in Ethics (24) -a critical analysis of different ethical perspectives and theories which interrogated themselves on a commune topic-), we have to examine minutely the possibility to use the utilitarian approach as a useful tool in GLGT problems. I shall analyse this topic by criticising the utilitarian logical dynamic in itself. I shall suppose that the utilitarianism premises are the correct ones: the moral value of a germline gene transformation is linked to its result; the human genome does not have a moral meaning in itself.

Utilitarianism's Principles

If human beings don't have a value in themselves, and if we suppose that the maximisation of utility (or minimisation of damage) is a positive principle in Ethics (linking utility to health), it fallow that human genetic identity (as individuals and as a species) is ethically insignificant. In this view GLGT can be judged by linking the positively of its therapeutic purposes to the increase of health in the patient (3, 6). Let's consider the utilitarian view on the relationship between the utility of GLGT with the consequence that this action determines toward the subject undergoing it. On a side we have the utility of our action -A-, from the other its consequences towards the patient or the future generations (1).

A's utility is the end of the disease. It determines an increase in the quality of life in the patient (2), and in a future society in which we will be not in condition of further applications upon A for treating the pathology. These data define the positive consequences of A. Now let's consider its consequence toward the subject who undergoes this transformation. His genome transformation determines the phenotypic expression of the bioengineered nucleus sequences. The genetic identity of the subject is transformed. This transformation will be inherited by progeny. If we assume that the number of subjects undergoing this transformation can vary from 1 to n (indefinite) -we can apply GLGT to an indefinite number of patients-, it follows that we will have repercussions, in the extensive sense, toward a huge number of individuals (27) (after 20 generations?). If we consider this problem by the utilitarianism approach, we need to define (and to calculate) the total degree of A's utility. This means that we have to consider (7, 14, 15):

We have to multiply these data for the number of A applications.

A's provisory utility is the sum U(A) of its possible results (es), as a function of the probability of realisation (prob)(3):

U (A) = prob(es1) x u(es1) + prob(es2) x u(es2) + ....prob(esn) x u(esn);

These data must be linked to consequences C(A) of this action:

C (A) = prob(es1) x c(es1) + prob(es2) x c(es2) + ....prob(esn) x c(esn);

The total utility degree U(A) is:

{U (A) - C (A)} x n applications (1< n < + ) (4).

The relationship between these two factors (utility-consequence) is the total utility degree of our action. The positive consequences are linked to U(A), the negative ones to C(A). Both these parameters need an explanation of their moral connotations. When I say "utility of GLGT" I define the treatment as a positive value. In parallel "consequences of GLGT" is a parameter which needs the clarification of its moral meaning. E.g. if I consider the genetic transformation as a "negative" consequence I shall link this believe to C (A) -other consequences could be: the repercussions on population genetics equilibria, the evolutionary dynamics, the impossibility of control of retroviruses plant, the impossibility of prediction of ectopic expression of bioengineered nucleus sequence etc. (26).-. In this sense when we are defining the total utility of GLGT we need to clarify both these parameters (U(A)-C(A)). If we don't do this examination we risk to evaluate GLGT by using an unbalanced analysis which clarifies the positively of GLGT by denying the existence of C(A) -or attributing to this parameter an insignificant moral value-. But is it sufficient for defining U(A)?

We have not defined yet the ethical meaning of this action. We have supposed that the first term U(A) (recovery) is intrinsically positive. This conclusion is linked to intuitive reasons: someone who is healthy has a higher quality of life than the sick person. But how the problem of the consequences U(A) influences the total positive value of GLGT? Utilitarian argument considers a genetic transformation of a subject as ethically insignificant, because it is made in Embryogenesis phases where a central nervous system is not yet formed (the Embryo does not have its own psychological identity). Because the embryo's identity is transformed in biological phases where we have not a differentiation in tissues, we have not reasons for saying that a genetic transformation changes something "for him" (5, 6) since he completes his development anyway (5). Since our Self-identity is linked to our self-awareness, the genetic transformation does not interact with the constitution of subject's identity. Also if a biological interaction exists, anyway the psychological identity of the subject will be respected (4, 6). May we accept this view?

Responsibility toward patients

I believe that this objection does not focus the heart of the problem. Even if Embryo X does not "feel" the transformation, anyway he undergoes a transformation (6). This means that X is subject to external actions that he may not have chosen (in the cases of therapeutic applications we may believe that X approves of the therapy because by the treatment his health is restored, but we cannot be sure that this would have been his choice), and that causes a genetic transformation in the self identity of X (4, 21, 23). The phenotype expression of the "transformed DNA", makes the subject different to "that which he should have been". This element can not be considered in a global moral analysis of A, because the subject does not have the possibility of choice. In this sense if we want to transform the germline gene identity of a subject we have to analyse this transformation as a "problematic" case which needs a moral clarification. Why suppose that the perceptive acts (capability to feel pain) can be considered as indicative conditions for choosing when and if a germline gene transformation can be done? Why not raise the problem of science's responsibility (22) toward this "transformed" subject by saying that his embryo-genetic phase does not present the formation of a central nervous system?

Responsibility toward future generations

We also have to consider also another problem. Because we have supposed that this genetic transformation is made on germ line cells (7), future generations will pay the consequences of this act. If GLGT causes the affirmation of a "negative" character in population genetic (a character which does not consent the fitness to environment); the "future subjects" will pay the price of GLGT's unpredictability. Let's consider an hypothetical situation. A person undergoes GLGT. His health is restored and his genetic identity is transformed. Another person undergoes GLGT for treating another disease. Both are cured. They have a child, whose gene identity presents an genetic anomaly. The combination of parental genome (transformed by GLGT) and "crossing over phenomena" determines in the child the formation of a particular nucleus sequence whose phenotypic expression has a catastrophic fitness value. This "artificial" character is inherited by its progeny. A mechanism starts whose result is the affirmation in population genetics of this "artificial" character -I say "artificial" because it is the consequence of artificial transformations of parental genomes- (20). In this case the utility of GLGT has been respected (the persons who undergo GLGT are cured), but this act caused a chain of events which determine negative consequences. Also if U(A) was "the treatment", the parameter C(A) is linked to the events which determine the consolidation in population genetic of this "no-useful" character. In this sense, if we consider my initial schema U(A)-C(A), because C(A) increases in time, the relationship between positive consequences -U(A)- and negative ones -C(A)-, has a big ambiguity. If the global utility of A is the relationship U(A)-C(A), because of C(A) increases geometrically (11), it follows that global utility of A, is inversely proportional to the C(A) increase. This means that the global utility of A is weakened (8).

We could object that also U(A) increase in time, because future generations will not need to treat this pathology, but I believe that this is not correct. When we choose to treat X by A, we have a single patient. Genetic heritage transmits his "transformed genetic identity" to progeny. A's utility to X is linked to his recovery, but "crossing over" phenomena show that his children will be sick only in case of homozygous persons. So they are only potentially sick, because they have statistical possibilities that the pathology will be not transmitted to them (or that it will rest "silent"). I believe that this allows us to say that if C(A) (genetic transformations) are directly proportional in time, U(A) follow only partially this dynamic. So C(A) has a bigger weight in the juxtaposition between U(A)-C(A). This analysis is linked to moral weight attributed whether to U(A), or C(A). But if we linked these to the utilitarian dynamic we have to value relationship U(A)-C(A) in logical terms, we have to consider the rational consequences of this juxtaposition. In this view C(A) -as I have deduced- has a stronger value than U(A).

How to evaluate the moral meaning of C(A)?

Another objection can be opposed to the utilitarian view. If the parameter U(A) can be intuitively evaluated, the second one -C(A)- has an non-intuitive value. Because it is really difficult to value the ethical meaning of an act by relating it to its progressive consequences in a vast temporal dimension (evolutionary time, future generations) (17, 22). We can only hypothesise this datum, and we can only attribute its moral weight in function of our ideas on the consequences of our action toward the future world. The philosopher D. Parfit (17) said that modern culture has translated in philosophical -ethical- terms the Keynes' economic dynamics -Ethical discount rate" (EDR)-. EDR is a phenomenon in which the value attributed to an action is inversely proportional to the time in that the consequences of this action will be paid. This means that the positively of our action must include in itself also the consequences in evolutionary time. We can think about a subject which undergoes a genetic transformation as a single subject, and we can value its sufferance in function of its sickness. We can decide to cure him by following the utilitarianism argument which said that the treatment is intrinsically positive because will determine an increase of his life-conditions; but when we pass from the level of a single to the species, the logical dynamic inducing to choose GLGT should have to be linked to the extensive repercussions of our action A in time. For example, a medical policy based on GLGT (let's think of its applications in the third world (9)) is not linked to the consequence toward the subject X, but also toward the global unity Cx (Cx is the summitry of the individuals undergoing A, and their progeny) (5, 6, 30). Because the numeric extension of these individuals increases progressively in time, it follows that the relationship U(A)-C(A) has in the last one the most relevant term for the definition of A's utility. This means that if we want to use the utilitarianism for evaluating GLGT, we have to clarify how the utility toward the patient can be linked to the consequences of the treatment toward the future generations, and how we can accept the argument of the "treatment" also in cases of potential pathologies.

Conclusions

In this paper I have analysed the utilitarianism views on GLGT. My analysis of the relationship "utility-consequence", emphasises that when we consider the positive result (the treatment in GLGT), we cannot extend it to the same act which produced the result. If we say health is a positive moral value, we cannot expand this "positive" to treatments "to live aside" consequences toward patients and future generations. When we are thinking about GLGT, also if we suppose that its therapeutic results are positive in themselves, we should have to link GLGT also to its consequences. We should have to think that possibility to obtain the result "treatment" (in GLGT) is linked to the probability of realisation of this HG application (this is the reason of my analysis of probability dynamics). Additionally we should have to clarify to ourselves that this act is intrinsically connected with the problem of its consequences because the genetic transformation will be inherited by progeny (this is the reason of my emphasis on consequences toward future generations). This last parameter is linked to a moral judgement, because if we decide that GLGT is positive in itself (because "treats" the patient) we consider morally insignificant the transformation of genetic identity, and we consider as an "acceptable" risk its possible repercussions toward population genetics and evolutionary dynamics. Doing that we deny our moral responsibility toward future generations.

I believe that if we critically want to define a moral analysis of GLGT, we cannot forget that anyway the positively of an act (the treatment) has to be linked to its consequences. This last problem is structurally connected to our analysis on GLGT. If we limit ourselves only to the emphasis of the positively of GLGT's therapeutic purposes, we risk to analyse this HG application only in symbolic sense. Because we attribute a moral value to GLGT whiteout considering its results. I believe, utilitarianism can be considered as an useful tool for evaluating the Bioethics problems of HG only if we accept treatment symbolically as a positive moral principle. But when we coherently apply the utilitarianism view on HG, we have to accept all HG applications (also the eugenic ones!) which need additional ethical analysis. For example, how may we analyse the consequence of GLGT? It is "right" that future society will be composed by bioengineered organisms? May we say that science's responsibility toward nature and future generation is linked only to the utility of its applications? How do we decide what is "utility"? I believe that utilitarianists have to clarify all these problems for guaranteeing the comprehensive bioethics analysis.

I know that this paper will receive much criticism. I only want to underline that my criticism of utilitarianism does not want to refuse the importance of its analysis on HG. I only say that I think (and this is my personal opinion) that utilitarianists should have to clarify this problem: how the problem of consequences toward future generations (and the patient) can be critically and pragmatically linked to the definition of GLGT's total utility degree? When this dilemma will be clarified, utilitarianists will enrich their studies on HG.

Notes

1. We have also the problem of responsibility of this actions -if it exists- (the problem of who can choose the pathologies to treat, and of the ethical meaning of human genome artificial transformation).

2. When I say "increase of quality of life", I mean that treatment restores the physiological functions of a person. In this optic, I don't want to say that treatment "always" improve the quality of life, and that a "sick person" does not have a "quality of life", I only say that when the physiological functions of a subject are restored he can have a benefit. This benefit increases subject's quality of life because determines an increase of his social, economical, hedonist possibilities.

3. I'm using the principle of "expected utility" which has been explained in Nozick, R., The nature of rationality, 1993, Princeton University. Press. , I.7; Nagel, E., The structure of Science, Harcourt, Brace and World, New York, 1961, pp. 47-76, Hempel, C.G., Aspects of Scientific Explanations, Free Press, New York, 1965, pp. 246-272

4. We have not solved the problem of the correct key to value the consequence degree of A. Must we use the probabilistic elements? How do we link this strong dynamic as the numerical one, with the possible consequences in terms of genetic mutations in the population dynamic, or in the ectopic translation of the required character? Do these two parameters invalidate the prediction logic dynamic of utilitarianism?

5. This objection has been made to me to Prof. John Harris.

6. On the ethical and biological meaning of Pre-Embryo's gene-identity transformation phases you can see: M. Salvi "Paradossi di identita', Biotecnologie e identita' personale", in Bioetica, Rivista interdisciplinare, Marzo, 1997, Milano, Franco Angeli eds., pp. 53-77

7. In case of somatic gene therapy, we the relationship between U(A) and C(A), is reflected only on the subject undergoing the therapy. In this case we have not a extensive repercussion of A, because the genetic transformation is not transmitted to the progeny. In the same time the subject can choose if he want the treatment. SGT is simply a treat.

8. If we analyse a genetic transformation in somatic cells, the utility degree of A is linked to the relationship U(A)-C(A) in the subject. This relationship will determine the moral meaning of A. In somatic cell therapies, we can accept the utilitarianism principle, and to evaluate the positively of A by considering the result of the treat.

9. This hypothesis has been discussed by Wood-Haper, J. "Manipulation of the germ line; toward elimination of major infectious diseases?", in Ethics and Biotechnology, edited by Dyson, A., and Harris, J., 1994, Routledge, London, pp.121 - 144; and Salvi, M., "Biotecnologie e Terzo Mondo, un problema di Giustizia", in Qualita' Equita', Rivista del welfare del futuro, Editrice Libereta' S.r.l., n.3, September 1996, pp. 111-123.

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