Capítulo de livro: DOMINGUES, Ivan. (edit). Biotechnologies and the Human Condition. Belo Horizonte, UFMG, 2011.

Genetic engineering and the present of the human condition 1 PROF. ALCINO EDUARDO BONELLA UNIVERSIDADE FEDERAL DE UBERLÂNDIA (UFU), CNPQ, FAPEMIG

RECENT DEVELOPMENTS IN SCIENCE AND GENETIC TECHNOLOGY RAISE PHILOSOPHICAL REFLECTIONS AND EVALUATIONS OF ETHICAL IMPLICATIONS OF BIOTECHNOLOGY, ESPECIALLY ABOUT THEIR EXPERIMENTAL AND CLINICAL USE.

SPECIFICALLY, I REFER TO GENE THERAPY WITH SOMATIC CELLS, GENE THERAPY WITH STEM CELLS AND PROSPECTS FOR THE USE OF GENETIC TECHNOLOGY FOR SO-CALLED HUMAN IMPROVEMENT (ENHANCEMENT)

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. SUCH REFLECTIONS AND EVALUATIONS

SHOULD BE PART OF OUR POSITION AND THE VARIOUS INDIVIDUAL AND COLLECTIVE DELIBERATIONS THAT WILL BE PART OF ANY SIGNIFICANT CHALLENGE FROM NOW. THE MOST PARADIGMATIC EXAMPLE OF SCIENTIFIC BREEDING IS THE CREATION OF THE HUMAN GENOME PROJECT, WHICH IDENTIFIED AND SEQUENCED THE GENES OF OUR SPECIES, TOTALING BETWEEN 30 TO 35 THOUSAND GENES, FORMING ROUGHLY 3 BILLION BASE PAIRS OF NUCLEOTIDES. THE PROTOTYPICAL EXAMPLE OF THE USES OF TECHNOLOGY IS TO USE GENETIC ENGINEERING AS A MEANS OF FINDING CLINICAL APPLICATIONS OF THE KNOWLEDGE GAINED FROM THIS AND OTHER GENETIC RESEARCH, APPLICATIONS USUALLY PERFORMED AS GENE THERAPY. THIS IS ONE OF THE NEW HUMANITARIAN CHALLENGES IN GENETIC IMPROVEMENT OR ENHANCEMENT.

It is common to distinguish these two applications from the main goal of curing diseases, disabilities or health problems, when we think of gene therapy and of the goal of improving the performance of human functions, beyond recovery or health maintenance and enhancement. First, there is our interest in finding new therapies for 1

Thanks to CNPq and Fapemig for supporting the research, and to Prof. Leonardo F. Almada for helping with English. 2 According DeGrazia, enhancement technologies are those used for improvements of human form or human functions beyond the use for restoring the health. (cf. 2005: 205-6). But this kind of biotechnology is not yet a widespread clinical reality. The ways for doing this with gene therapy are either “gene correction” directly, or “gene repair” by the cell’s mechanisms itself. (cf. idem, 212)

serious problems; secondly, the need to preserve and promote human progress in general by scientific, technological and human advancement, particularly, to aid in the development of new life forms with many human functions, especially the cognitive. On the other hand, there is also our interest in ways to prioritize the safest, most responsible and socially just ways to deal with biotechnology. Indeed, although no one can reasonably deny the importance of gene therapy for all those affected by serious diseases and for those who know the value per se of scientific and technological development, it seems both unwise and unreasonable to ignore important questions about genetic engineering, especially in light of the experience of relationships between physicians/researchers and research subjects/patients, as well as between a government and its citizens. In addressing the topic in general terms, it is easy to delineate two groups of positions: one, in favor of the use and supportive of the latest biotechnology; the other, contrary to this, in favor of banning or restricting uses of biotechnology, whether temporarily or permanently. In general, those basically in favor of the technologies, and beyond the values already listed above, usually argue the importance of the autonomy of individuals and couples in the face of government and doctors' influence (in matters of reproduction, for example), and point out the possibility that intelligent regulations by the government, corporations and professions, coupled with advice and clarification for individuals may be sufficient to monitor the uncertainties of new techniques and negative consequences for society. These are reasons given to justify approving the use of biotechnology for enhancement, including cloning of any type (i.e. reproductive) 3. Opposing positions argue that, in addition to the problems listed above, we also encounter fears and criticisms more specifically in relation to an alleged loss of genetic integrity and authenticity of the species, as well as a more radical degeneration of democracy and the delicate state of equality between human beings (patenting of life, genetic elitism and inequality, discrimination or social pressure against the excluded); as well as attacks on human dignity or basic human rights. The agenda of specific and important questions appears to include: security applications, in terms of damage to health in patients or healthy subjects submitted to genetic research protocols (in terms of intervention); ensuring the autonomy of capable

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On this alleged distinction, see Dworkin 2005, chapter 13; and Bonella 2006.

human individuals; the structuring, maintenance and effectiveness of medical and social practices that promote autonomy and due care (to avoid unnecessary damage and protect the best interest of patients – those able and particularly those unable to protect their own interests, such as children); relations and consequences related to the system of health care (coverage; availability of interventions at all or not; investment priorities; reductionism of the therapeutic agenda or exacerbated and disorganized extension of clinical practice); relations and consequences related to the social system (reminiscent of the eugenic practices in the context of Nazi ideology, complicity with questionable social practices, the necessity for social administration, the relationship to social justice, the risk of pressure and “social” blackmail threatening autonomy and democracy); the implications for the notion of human identity and dignity. (cf. DeGrazia 2005: 215-228). The first item on the list, security, concerns both genetic engineering as therapy and human improvement/upgrading: the first question that intuitively presents itself to most laymen and experts is about the likelihood of harm and benefits that the intervention will cause. This question is trivial from a traditional point of view, but we address it here because it relates to both types of uses of genetic engineering and can also shed light on how to properly assess the newest uses, enhancement, and therapies that focuses on stem cells (which involves risks to future generations). In addition, the assessment of damages and benefits is a question which involves ethics in a research and experimentation, including the ethics of the involving animals, which are usually thought of as the best means to avoid uncertainties and risks. Genetic engineering is in its infancy and its application emphasizes, among other things, the importance of research that aims to identify potential damage and ways to avoid them, but this fact will imply a type of intervention or experimental use of the technique, putting us in a dilemma: we not want to put patients with urgent medical needs under unnecessary risks, and then we only approve interventions when we know the risks. But to know about the risks and monitor them we need research which involves the intervention. The intervention may involve more damage or risks in this early, experimental phase, which is a strong reason to not approve research protocols with unknown techniques. This situation keeps us without knowledge of the risks, consequently keeping patients in general suffering from the diseases, which, in turn, is a strong reason to accept the risks of research. What to do about this dilemma?

In the case of genetic engineering, risks and uncertainties can be cataloged, according to Buchanan, Brock, Daniels and Wikler (2006), as follows: (A) risks in general on the relative inability to put a gene in the proper place within a chromosome or remove a defective gene. We do not have yet vehicles (vectors) sufficiently accurate to make such delivery or removal, and therefore genetic interventions potentially allow unintended genetic effects with unknown risks. Not only is it possible to fail to achieve the desired result, but we can cause other problems, as well. (B) The (A) problem is more intense in the case of germ-cell therapy, because unforeseen damage can be transmitted to future generations. (C) the use of genetic engineering for enhancement would take such risks, as in (A) and (B), without any expected benefits, as in gene therapy of somatic cells. In the case of therapy, non-intervention involves the risk of harm from identified diseases and ill health, but in the case of genetic improvement, the risk is the non-development of normal or suboptimal functions of the human beings. In addition, may need to intervene in multiple genes, which would geometrically increase risks in the case of the enhancement. (D) Following intervention there is uncertainty and risk involved in the interaction of genes and their products with each other and in their relationship to the environment of the “re-engineered” organism to produce the expected biological trait. There is also (E) uncertainty about the integration of the development of a function (short-term memory, for example) so that an improvement in overall functioning (number of coordinated functions), not its deterioration, by creating interference (intrusive, uncontrolled memory affecting other learning functions). (F) A number of experiments that would mitigate or eliminate the risks would be unethical, for example, involving a future generation that cannot give consent (idem, pp.101-194). A possible position on these risks would be to allow, cautiously, some research and methods of gene therapy in somatic cells and in adult patients whose weighed evaluation of benefit and risk could justify the intervention and consent to it, meanwhile prohibiting intervention in germ cells and interventions for human improvement by genetic engineering. This is probably a very prevalent position, but it does not seem to be the only one compatible with the ethical principles of respect for individual and responsibility without doing harm. The cited authors defend a model that is less prohibitive. Let us consider, therefore, another position, which disagrees with the current level of precaution and ethics in prevalent research, but is more liberal in

relation to risks. It is possible to insist that we should take risks, especially in the case of gene therapy, but also in the case of improvement. Lowenstein (2005), for example, states that any new medical technology will always depend on knowing what works and what does not. Experimentation, for this purpose, is essential. For him “clinical trials in early stages are human experimentation.” Therefore, trials should be part of the development of genetic engineering, as they already are part of pharmacological research (clinical) for which the initial phase is essentially about toxicity and not about the effectiveness of treatment. The same should happen with research in genetic engineering, and our precautions against mere experiments should be eliminated as inappropriate emotional responses (idem, p. 25). Given the complexity of genetic engineering and risk assessment, informed consent and ethical rules would be very limited, and the patients would not have to be sufficiently informed. For Lowenstein, societies, rather than individual patients, need to decide whether we want to proceed with human clinical trial in the absence of evidence of its effectiveness, assuming that “the only way to progress and improve medical treatments is through continued human experimentation” (idem, p. 26). The question that uncertainty presents us with is not when it is ethical to start an experiment, but when it is ethical not to start one. To this author, societies must assume the ethical risk to decide whether new tests and technologies will be implemented, because if such implementation carries a risk, not doing so also implies a serious danger (do not develop new treatments). Remember, we do not make negative judgments in relation to current vaccines and deny their benefits despite the nature of the initial tests on orphans, mentally retarded people and citizens of the third world, whose status as human beings, according Lowenstein (idem, p. 29), were more easily disrespected. He also suggests that current caution in relation to gene therapy research may be judged immoral in the future, as well as our fear of something unexpected in relation to enhancement (idem, p. 30). It is possible that fear and caution should be approved, and it is amazing how the views held by Lowenstein clash with the position held today in terms of ethics in research and clinical medicine, especially the principle of never treating as mere means the individual subject of research, but always and simultaneously as an end in itself, to

use Kantian language, or, recalling the United Nations Statement of Bioethics and Human Rights, that the interests and welfare of the individuals should have priority over the sole interest of science or society (see article 3, b), at least as general rules more conducive to protecting the subjects of abuse and exploitation. In response to Lowenstein, we can say that this principle does not eliminate research and intervention, because they do not relate to question of “what” to research, but the “how”. We do not intend to avoid any risk at all costs; neither will we continue to prohibit or limit interventions but to explain and justify “what” risks we ethically want to take, to what extent and how long. The protective principle of our current orthodoxy (at least in the case of human subjects research and therapy), as outlined above, combines requirements of caution and freedom to develop medicine: to respect the free and informed consent of the subject, and maximize the benefits expected by avoiding or minimizing probable harm, so that the research design is, as far as possible, consistent with the treatment, i.e., clinical benefit of the involved subject 4. If we do not refrain from vaccination this does not mean that we approve the use of human orphans as “guinea-pigs”: in the absence of a reasonable alternative to current medicine, and if we are not agreeing to the practice of such test-subjects (rejecting it for the present and the future), I do not see taking the vaccine as complicity in such an inhumane practice. Similarly, we can criticize the lack of alternative options to the current protocols involving animals, alternative protocols that could possibly result in the same relevant knowledge, and even we take the medicines produced by the current system that are necessary (because there is no alternative for consumers). We can put the questions in terms of degree of responsibility, and not as all or nothing. Moreover, let us consider what exactly it may mean that society and not the individual patient should decide to take risks and what risks they may be, with new tests, while, at the same time we want to respect individual rights and avoid the kind of abuses committed in the past regimes during which such rights were not being protected? Perhaps it is 4

Perhaps the same applies for the ethics of involving non-human animals in experiments and research. Today we accept the restricting rules on ways for experimenting, summarized in the precept to replace, reduce and refine animal use, which does not eliminate research, even if it certainly makes more difficult, in some ways, the maximization of the experimentation and the speed of testing that would be possible without such restrictions. Extending the position taken for humans to other animals will most likely be the only one that can prevent abuse and safeguard their well-being. Perhaps, we must reform our practices and only use animals if they, as subjects of the research, can benefit in some way from the procedures, meaning that the research would, in itself, become a kind of therapy. If that suggestion appears strange, it would be wise to remember that this is the current legislative position adopted for human patients, especially for vulnerable patients (children, disabled, elderly, chronically ill, etc.)

sufficient for future generations to know that we have made efforts to reconcile medical developments and respect for individual rights, and that we were more cautious (assuming that we are) than we could have been, precisely because we take seriously the violations caused by lack of cautions in the recent past. This position, however, does not seem prohibitive and does not need to inhibit research in genetic engineering, even germ cell therapy and engineering for improvement: cases may exist in which interventions are obligatory even if we take the mandate “do no harm” seriously, for example, when germ cell therapy is the method used to cure genetic damage with very low probability of future genetic problems. So, the simplified division into two opinion groups should instead remember to include intermediate positions which approve (or disapprove) uses of genetic engineering under certain conditions and with caution. This approach, moreover, seems to be the best starting point or initial hypothetical evaluation, taking seriously the more specific questions raised by genetic engineering which are relevant for liberals and conservatives. At least liberal governments and liberal people would do better to consider each case individually, according to cautious principles. This is so because liberals are usually strongly allied to individual liberties and choices, and egalitarianliberals (the most coherent kind of liberalism), whose egalitarianism covers more issues, such as fairness in society. The use of genetic engineering for reforming non-ethical behavior may also be considered a kind of duty. In general, we have accepted the fact that parents and governments have been using many kinds of phenotypic interventions with the same goal. Why not genotypic interventions if safe and based on human rights? 5 Our empirical and evaluative problems are to find these safe methods of research and clinical applications.

References: Boleyn-Fitzgerald, P. (2005). “Experimentation on Human Subjects”. In: FREY, R. G. & WELLMAN, C. H. A Companion to Applied Ethics. Oxford: Blackwell.

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Professor Julian Savulescu supports enhancement as even a moral duty, assuming it meets certain moral conditions as: the techniques should be safe, not harmful to others, justly distributed, well-being based, and consistent with an open future – the last two applying specially in the cases related to children. See Savulescu, 2006.

Bonella, A. E. (2006). “Clonagem”. In: Marques, A. (ed.). Dicionário de Filosofia Moral e Política. Lisboa, Universidade Nova de Lisboa. (www.ifl.pt/main/Portals/0/dic/clonagem.pdf ) BUCHANAN, A.; BROCK, D.; DANIELS, N. & WILKLER, D. (2006). “WHY NOT THE BEST?”. FROM CHANCE TO CHOICE, GENETICS AND JUSTICE. CAMBRIDGE: CAMBRIDGE UNIVERSITY PRESS. DEGRAZIA, D. (2005). ENHANCEMENT TECHNOLOGIES AND SELF-CREATION. IN: ______. HUMAN IDENTITY AND BIOETHICS. CAMBRIDGE: CAMBRIDGE UNIVERSITY PRESS. DWORKIN, R. (2005). “BRINCAR DE DEUS: GENES, CLONES E SORTE”. IN: ______. A VIRTUDE SOBERANA. SÃO PAULO: MARTINS FONTES. LOWENSTEIN, P. R. (2005). GENE THERAPY FOR NEUROLOGICAL DISORDERS: NEW THERAPIES OR HUMAN EXPERIMENTATION? IN: BURLEY, J. AND HARRIS, J. (ED.) A COMPANION TO GENETICS. OXFORD: BLACKWELL PUBLISHING. SAVULESCU, J. (2006). GENETIC INTERVENTIONS AND THE ETHICS OF ENHANCEMENT OF HUMAN BEINGS. IN: STEINBOCK, B. THE OXFORD HANDBOOK ON BIOETHICS. OXFORD, OXFORD UNIVERSITY PRESS.