Canadian Medical Association Journal 1996; 154: 927-929
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Introduction
The discovery of DNA created a new chapter in the history of science: the genetic age. Its greatest effects have been felt in medical practice, where traditional diagnostic tools and medical therapies are rapidly being replaced by more sensitive and specific genetic methods. Also affected are the medical humanities, since the genetic age has the potential to revolutionize "the traditional concepts of man, God and creation."[1]
The responsibility for harnessing this potential lies entirely within our hands, and just how well we write this chapter of our history -- if we even choose to complete it -- will largely determine the future of the human race. Because the science of genetics can have such profound effects, society must define parameters to provide an ethical framework within which to make decisions on genetic issues. Such a framework must be flexible enough to accommodate individual morals, opinions and beliefs, while incorporating social mores.
Since consideration of the entire scope of the genetic age is not possible within this essay, I will attempt to provide an ethical analysis of a particular facet of the genetic age in which health professionals are the key players: gene therapy.
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Gene therapy -- a definition
A gene is a functional segment of DNA that specifies, or assists in, the expression of a particular phenotype. Therapy, according to the Oxford dictionary, is a "curative medical treatment"; this implies the remedial treatment of disease. Therefore, gene therapy is, in an elementary sense, a remedy for disease and, in light of trends in preventive medicine, a method for preventing disease by genetic manipulation. These methods fall into two broad categories -- somatic-cell therapy and germ-line therapy.
Somatic-cell alteration is a form of genetic remedy that does not affect gametes but simply changes a diseased person's form by manipulating the somatic cells that cause a disease. This form of therapy involves altering the genetic makeup of only those cells that cause disease -- it can be considered "genetic surgery."
The second type of genetic therapy involves permanent changes to a person's genome by germ-cell alteration. This procedure, known as germ-line gene therapy (GLGT, or genetic engineering), results in modification of heritable characteristics. These changes can be passed on to progeny.
The former therapeutic practice appears to require relatively little ethical consideration, but the latter has created dilemmas for those making professional, social and personal ethical judgements. Some authors have chosen to distinguish between GLGT for treatment of disease versus GLGT for enhancement purposes.[2,3] I consider both under the same heading, as the latter represents the fullest potential of the former. I wish to consider whether genetic engineering in humans ought to be practised.
The ethical problems raised by genetic engineering stem from societal and individual implications, issues of control and the biologic impact of genetic manipulation. Various ethical principles, including autonomy, beneficence and nonmaleficence, can be invoked to delineate the nature of these factors.
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Creation of inequality and discrimination
One of the most widely accepted rules of societal ethics is that which opposes discrimination. Germ-cell therapy, by its corrective nature, presupposes an inequality among genotypes that can lead to elitism.[2,4] This "genetic superiority" can lead to discrimination on the basis of genetic traits, which is unjustifiable in society. Of the several arguments proposed in support of germ-cell therapy,[2,3,5] one suggests that knowledge of genetic traits can lead to the establishment of equality -- for instance, by offering compensation to genetically "inferior" people. Yet this argument is fraught with complications, especially when aspects of control are addressed.
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Privacy
This is an extremely controversial issue whenever gene manipulation is discussed. Privacy is "a state or condition of limited access to a person";[6] when privacy is defined as a right, one is obligated to respect it. The genome is an integral part of a "person" and consequently any manipulation of it without consent constitutes a violation of a right.
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Cost-benefit analysis
The cost-benefit approach to ethical problems is commonly used to judge the practicality of a procedure in purely economic terms. The problem is that cost-benefit analysis presupposes a relatively clear definition of "benefit" which, in the case of GLGT, is rather vague. Since genetic engineering will affect future generations, it is difficult to determine what will be beneficial to progeny in light of the risks posed by GLGT. One major risk is the questionable outcome of any form of genetic engineering because of the extremely complex nature of DNA. Further, each member of each generation of each society has different priorities and consequently different views of what constitutes a benefit. This is another difficulty of cost-benefit analysis. By what form of arithmetic can we evaluate the aspirations of people we do not know in a future that we have no way of predicting?[4]
Whereas arguments have been raised using the principle of beneficence, supporting a prima facie obligation to promote disease-free life,[3,5,7] GLGT may not assure such a benefit for progeny. It is certain, however, that germ-line therapy infringes upon rights of autonomy and liberty in future generations. It is logical, therefore, to act so that a certainty is not sacrificed in exchange for a probability. By this line of reasoning, GLGT is wrong.
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Autonomy
The nature of GLGT is such that changes made now will be passed down through generations. In making a decision today, one has made the decision for generations to come, and in doing so has disregarded the autonomy of children of the future. These children may face difficulties because of genetic alterations that were made without their input or consent.
Consider a child who is a product of GLGT, who must accept all implications of a procedure performed generations ago. If she is aware of the germ-line alteration, a series of psychologic problems may arise from the knowledge that an integral part of her being is, in essence, not natural.[4] This personality dilemma could conceivably spawn anger toward her parents and any other proxy decision makers who may have disregarded her autonomy.
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Beneficence and nonmaleficence
Beneficence and nonmaleficence have an almost inseparable relationship in the Hippocratic oath: "I [the physician] will use treatment to help the sick according to my ability and judgement, but I will never use it to injure or wrong them."[6] Genetic engineering has the potential to wrong or harm a person, perhaps even more than to benefit. These potential wrongs should provide sufficient basis for a physician who abides by a code of professional ethics to reject GLGT.
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Control: drawing the line
Before any progress can be made toward "drawing the line," where should the line be drawn? I think there is a relatively simple answer - draw the line between somatic-cell alteration and germ-line alteration.[8,9] It appears that this approach has been adopted by the Recombinant Advisory Committee (RAC)[10] and the European Research Council,[11] as neither has entertained experimentation with germ lines.
To support the use of germ-line therapy, Baird[2] made a distinction between genetic alteration for "prevention" versus alteration for "improvement." The maintenance of this separation relies purely on regulatory bodies, as the technologies are similar. The "slippery-slope" argument should be considered here, with the slope representing progression toward human enhancement. Proponents of GLGT claim that the progression can be halted midway down the slope if the correct regulatory measures are in place.[2,3] While this theory might work in an ideal world, there is a risk that unscrupulous people may disregard regulations.
The issue of who is to govern GLGT poses another ethical dilemma. Oddly, the lack of a comprehensive answer is another justification for opposing GLGT. Without a controlling body to limit the extent of genetic manipulation, there is substantial societal risk that scientists could alter genes as they see fit, perhaps indiscriminately. The RAC has been established in the United States to oversee experimentation in this field; however, its function as a governing body is yet untested.
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Just allocation and distribution
Distribution dilemmas are beginning to overwhelm medicine and medical research because demand usually outstrips supply; inevitably, this will be the case with GLGT. Who will receive treatment, and for what reasons? The answers can only be provided by an effective governing body, and none currently exists.
Proponents of GLGT may argue that should we reach the stage where enhancement is possible, genetic manipulation can be used to eliminate certain problems in society. Consider pollution -- it is plausible that by genetic alteration, people could become resistant to some effects of pollution. However, gene therapy would not solve the problem -- it would simply mask it and even compound it.
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Biologic significance
For those who believe in evolution as postulated by Darwin and Wallace, it is understood that variability affects the viability of a species; those with greater variability have a better chance of perpetuation in a changing habitat because of their ability to adapt by the mutation of genes.
Genetic manipulation could have a homogenizing effect on the human gene pool, with possible detrimental effects. Many supporters of gene therapy argue that because human decisions are affected by a multitude of influences, variety of outcome is inevitable and heterogeneity is maintained. This argument can be countered by what society dictates. Consider a genetic disease: it is probably safe to assume that most societies would support elimination of the disease, resulting in the loss of yet another variable -- the disease gene - in our gene pool. Should this occur with increasing frequency, the human race would begin to lose its variability and, subsequently, its ability to adapt to a changing environment.
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Conclusion
"Human heredity is intricate and mysterious. We must face the prospect of intervention with awe, humility and caution."[1]
That statement must always weigh heavily in any consideration of genetic manipulation, regardless of the orientation of one's ethical compass. I have attempted to discuss some of the dangers inherent in germ-line gene therapy. I believe that GLGT violates various principles, including autonomy, beneficence and nonmaleficence. In addition, there are logistic problems involved in the establishment and control of a governing body that could maintain a line between alteration for enhancement and alteration for prevention of disease.
Rather than concerning ourselves with establishing such complex bodies, we should simply prohibit germ-line therapy of all kinds and make do with somatic-cell therapy because the potential for abuse and the danger to society is much less evident. As a wise man once said, "Why ask the way to a village that you have no intention of visiting?"