onder redactie van mgr.prof.dr. E. Sgreccia, prof.dr. W.J. Eijk, P. Garrett, MA, prof.dr. J.P.M. Lelkens, mr.dr. P.W. Smits

Ⓒ Katholieke Stichting Medische Ethiek 1997

Hoofdstuk V: The status of the human genome: is it ever licit to modify an individual’s genome?

Hoofdstuk V uit “Het embryo: Iets of iemand?”, onder redactie van mgr.prof.dr. E. Sgreccia e.a., Colomba, 1997
door P. Garrett, M.A.

The human genome is a biological entity which comprises the three-billion-letter genetic code contained within the nucleus of the typical human cell. The biological raw material of the genes which contain this genomic information is the deoxyribonucleic acid (DNA) molecule. This molecule is best envisaged as a twisted ladder, with uprights composed of chains of sugar and phosphate groups, while the rungs consist of bases sticking inwards towards each other. These rungs of the DNA ladder form properly only when one pyrimidine base plugs into one purine base, which results in fixed proportions of one adenine to one thymine, and one cytosine to one guanine pertaining throughout the genome. These organic bases, along with their ribonucleic acid (RNA) cousin uracil, encode a1l the information which makes us into physical human beings.

During the 1960s, geneticists discovered that the chromosomes are not uniform but are made up of coding sequences which specify proteins, ‘control’ sequences (acting as switches for structura1 genes) and areas which contain base pair sequences with no obvious function. We now believe that the human genome contains 80-90,000 actual genes which code for proteins.

The high-profile Human Genome Project seeks to ‘write out’ the entire sequence of genetic letters: those which generate the proteins that constitute our physical bodies (exons) and those other sequences which do not (introns). When this task is completed, clinical geneticists will search out genetic ‘spelling mistakes’ as a prelude to genetic engineering treatments. Technologies will then be developed not only to repair dysfunctional parts of the genome, but also to enhance ‘normal’ ones. The technological barriers in this area are considerabie, but so is the scientific motivation to overcome them. It will be important to refer back to this repair/enhancement distinction later when discussing the ethical status of the genome.

At this early stage the Human Genome Project is ‘merely’ trying to produce a standardized human genome which will not be the genome of a particular individual. Around the year 2010, human genome studies will progress to the analysis of multiple genomes, belonging to specific individuals, and the developing fields of genetic screening and genetic counselling will have to struggle to come to terms with the implications of this.

1. Status of the human genome

Looking at the ethical status of the human genome, one approach is to proceed by analogy with the debate over the ontological and moral status of the human embryo. Indeed, this was the approach taken by the Cathollc philosopher Luke Gormally when he was asked to speak on the status of the human genome in Rome, in 1995. (1)

For Gormally, the individual human genome. should be thought of as the fundamental information-bearing structure, within a complex organ of development and heredity, through which an organism exercises its natural powers of growth and reproduction. The functions of this genome have a determinate role in the formation of the human body, and an essential role in the transmission of an organized body of specific potentialities wich are apt for actualisation in a living human being through God’s creation of a rational soul.

Gormally argues, and I think rightly, that the ontological status of the human genome is rankable somewhere between that of the human embryo and that of a single human organ. Thus, while we do not owe a duty of care to a particular human organ, we do owe such a duty to a human embryo. According to Gormally, it is possible to locate the moral status of the genome somewhere between these two extremes.

Clearly, such an analysis affords an important role to the human individual’s genome and allows concepts and argument to be imported analogically from two well-developed areas of moral philosophy.

In order to make this qualitative comparison more precise, Gormally goes on to remind us of the ‘causal role’ wich each individual genome plays in a person becoming the living bodily being he is. By equating acceptance of the life given through parents, to acceptance of a particular genome, Gormally leaves us in no doubt as to the ontological and moral importance of each individual’s genome. In fact, Gormally’s understanding of the genome’s status leads him to formulate a significant final statement: “I have come to think that understanding what [the genome] is gives us some reason for thinking that modifications of the genome designed simply to alter non-pathological limitations are contrary to moral wisdom”. (2)

This allows that genetic modification may be licit as long as it aims at the correction of a pathological limitation. This type of demarcation will roughly equate to the separation between curative and enhancement engineering and will necessitate a close definitional analysis of the term pathological. This refined analysis is to be welcomed, but will always leave a grey area between the pathological and the non-pathological. Gormally is right to remind us that those who destroy the distinction, or abandon the intellectual effort of distinguishing, ‘destroy the possibility of thinking coherently about what is required for acceptance of the particular bodily life which each of us has been given.’

2. Excavation of categories drawn from theology and ethics

An alternative approach might involve the excavation of categories drawn from the disciplines of theology and ethics. For example, Joseph D. Cassidy and Edmund D. Pellegrino, writing in the International Journal of Bioethics (3) have developed their perspective on human gene therapy onder the following six headings: accountable stewardship; preservation and protection of the nature and destiny of humankind; respect for persons never merely the means of human experimentation; equality of ‘value’ of each person and, finally, charitable justice in distribution of resources. This treatment of the issue has obvious strengths and weaknesses. lts key strength lies in the disentangling of themes and ideas, while it suffers from what appears to be a lack a coherent and systematic theological under-pinning. This weakness is in large part due to the severely compressed format of the article, but it does lead to statements which cry out for further clarification. For example: “Biblical stewardship begins in Genesis 1-3 where we are shaped in God’s image so that He shares with us, as His intelligent and free co-workers, the co-operative care and use of creation… God commands everyone (through Adam) to conserve and cultivate (Gen: 15) a creation already adapted to human needs yet still perfectable by our creative efforts. He assigns to us the right preparation thereof by the precepts and practice of the works of mercy (Matthew 25: 34-46). Consequently when Christians employ genetic engineering technology within ethical constraints, they fu1fill the imperative of responsibIe stewardship”. (4)

The italicised terms require considerable unpacking if this statement is to escape a question-begging cul-de-sac. In fairness, Cassidy and Pellegrino are acutely aware that all the resources of the Catbolic tradition will need to be brought te bear on these complex ethical problems. They suggest that: “In this crisis of ethical orientation, the Catholic Church speaks on life’s meaning from a global perspective as the representative of a great moral tradition, capable of shedding light on ‘values’, of suggesting models of reasoning on difficult medical and societal questions and finding articulated solutions to hard cases like the moral applications of engineering the human genome.” (5)

In spite of the spatial constraints, Pellegrino and Cassidy provide a useful and delicate balancing act between ’the desire for learning as a desire for God’, and the ‘priority of ethics over technology’. We are steered towards occupation of the ‘middle ground’ between blind acceptance of every scientific ‘advance’, on the one hand, and total rejection of ‘responsibie and humane scientific progress and therapeutic treatments of genetic disease’ on the other. Pellegrino and Cassidy’s conclusion calls upon us te distinguish the practical virtues of our ability to manipulate the genome, from the moral dangers such artistry may entail, in order to affirm a technology at the service of man. Such an outcome is, for Pellegrino and Cassidy, achievable because those who apply the ‘norms of right reason’ to the field of genetic modification will abjure the subordination of the human person to mere technology.

3. A taxonomy of the problem

The most fruitful approach to this difficult ethical problem of deciding upon the limits of genetic intervention, is to begin by producing a taxonomy of the problem. The more classificatory distinctions developed in the foundations of an analysis, the better the analytical superstructure is likely to be.

Most writers try te distinguish enhancement engineering from mere repair engineering, but specialists tend to distinguish a third category (6) or expand upon caveats. (7) Eijk argues convincingly for the additional category of prevention engineering to cover cases where genomes are modified to prevent future damage. In the bio-medical part of his thesis he discusses the insertion of genes into liver cells of rabbits, encoding the low density lipoprotein receptors on the surface of liver cells, so that they may serve to take up cholesterol from the blood into the liver cell. Later, in the ethical part of this work, he speculates: “Perhaps this procedure could become a therapy for humans who have a deficiency of these receptors, and consequently have a high concentration of cholesterol in their blood, rendering them prone to atherosclerosis, especially ofthe coronary arteries.” (8)

The category of preventive genetic engineering has its place in an accurate taxonomy of the field. Future studies will be clearer if they employ this tripartite system instead of the traditional bipartite one.

Peterson’s insight seems equally valid when he writes: “If one or a combination of the definitions of health and disease that have changing applications is more convincing, there may still be a clear conceptual distinction between cure of disease and enhancement of capacity at any given time, but its application would vary temporally. The line of division would move over time. What would be ruled enhancement of capacity at one time might well fall under cure of disease at a different time … the applied result of the distinction would be conceptually consistent but not fixed in application.” (9)

lt is noteworthy that Eijk does not provide a full discussion of the problem of defining disease but is well aware of the importance of this aspect of the field of inquiry. Gormally claims to be employing a relatively narrow, Aristotelian conception of health according to which health is the ‘wellfunctioning of the bodily organism as a whole’. Usefully, Peterson dedicates over 20 pages to the definitional problem itself (10) – a feat of intellectual honesty which imports analytical humility into the field of view.

Apart from the classifying of ‘objectives’ under the headings of cures, preventions and enhancements, we must also distinguish ’target tissues’ according to whether they are somatic or germ-line. This distinction is now so commonly used that politicians and members of the general public employ it in their discussions of genetic engineering. Some writers have expressed doubts about the supposedly hermetic seal between the two types of tissue on the ground that delivery systems and vectors are so poorly understood and, more importantly, controlled, that a putative somatic treatment might inadvertently result in germ-line changes.

4. Analysis of moral agency according to the means-end model

Even an exhaustive taxonomy of ’target-tissues’ and ‘objectives’ will not provide an analysis of the acting person or his/her acts. To make such a ‘moral’ assessment we must overlay our two dimensional taxonomy with a framework for the analysis of moral agency.

Indeed, Gormally touches upon one aspect of this dimension when he comments upon enhancement genetic engineering by suggesting that: ” …. even if the suggested mode of carrying out the modification were not in breach of other moral principles and did not involve unwarranted risks, it would still be unacceptable as involving a wrong attitude to a particular living human being in the particularity of his or her bodily existence.” (ll)

The proposed engineering on the human genome will be adjudged licit only if both the methods and the intentions, of the researcher, parent or other agent, are morally acceptable. In the words of Pope John Paul II: “I approve and support your worthy researches. I reaffirm that they must all be subject to moral principles and values which respect and realise in its fullness the dignity ofman.” (12)

A year later, addressing the World Medical Organisation, the Pope distilled the principles which would have to be respected if genetic engineering was to be licit.

  1. The dignity of the human person must be respected by safeguarding man’s identity as corpore et anima unus.
  2. The methods used must not affect the bodily and spiritual union of the parents in procreation.
  3. Manipulations to create genetic under-classes must be avoided.
  4. Fundamental motives must not aim at a reductionist and materialist conception of man.
  5. The ‘liberty and autonomy’ of the human person must not be violated. These paraphrased guidelines are simply the seeds from which a more complete analysis of the liceity of genetic engineering may emerge. Eijk observes that these guidelines do not explicitly rule out all enhancement genetic engineering, but he goes on to remind us that the document Donum Vitae admits of no exceptions, and rejects every attempt at enhancement of human qualities by genetic engineering: “such enhancement manipulations are contrary to the personal dignity of the human being, his integrity and his identity. Thus they can by no means be justified by the eventual beneficial consequences for future mankind. Every person has to be respected for himself: in this the dignity and the right of every human being consists from his origin.” (13)

All such stipulations amount to limitations on the range of genomic modifications which may be deemed licit. In any particular proposal it will be necessary to evaluate methods, intentions, attitudes and effects to arrive at a judgment. This caseby case analysis is well suited to the rapidly altering science of genomic modification.