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SPECIAL ISSUE Human Transgenesis: Definitions, Technical Possibilities and Moral Challenges Flávio Guimarães da Fonseca & Daniel Mendes Ribeiro & Nara Pereira Carvalho & Mariana Alves Lara & Antonio Cota Marçal & Brunello Stancioli Received: 28 December 2011 /Accepted: 12 April 2012 # Springer-Verlag 2012 Abstract In this article, we examine the ethical implications of human transgenesis by considering the phenomenon in its larger evolutionary context. After clarifying the concept of transgenesis, we show that rather than unprecedented or unnatural, trans- genesis is a common aspect of the evolutionary process that has likely affected all extant living animals, humans included. Additionally, we demonstrate that human transgenesis is technically feasible and that the moral barriers to it are mostly based on irrational fears premised on distorted and unrealistic views of “human nature”. Furthermore, we suggest that transgenically modifying persons might be morally preferable to relying blindly on the “natural lottery”, and that it is possible to do so in an ethical and responsible manner. Keywords Transgenesis . Human enhancement . Human nature . Good life Ethics and technology 1 Introduction Humanity is on the verge of a global revolution in health care. With advances in molecular and genetic approaches toward understanding and treating disease, a plethora of new possibilities for improving human well-being is emerging. Some of these possibilities regard the so-called human enhancements—technological Philos. Technol. DOI 10.1007/s13347-012-0074-7 F. G. da Fonseca Departamento de Microbiologia, ICB, UFMG, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil D. M. Ribeiro :N. P. Carvalho :M. A. Lara : B. Stancioli (*) Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil e-mail: brunellostancioli@gmail.com A. C. Marçal Pontifícia Universidade Católica de Minas Gerais – PUC/MG, Belo Horizonte, Minas Gerais, Brazil interventions into human biology that enhance, change or create functional capabil- ities potentially beyond the “normal” human range (cf. Savulescu et al. 2011). Whereas the idea of human enhancement is in itself controversial, trying to perform enhancements by means of transgenic interventions may border on taboo.1 Interfering with genes suggests interfering with the course of evolution, blurring the boundaries between species and permanently tainting human nature. Thus, if most forms of human enhancement raise concerns about the boundaries of what should be regarded as human, transgenesis will only reinforce these concerns. Transgenesis is not well understood by most people. To critically assess the moral implications of transgenic interventions on the human genome, it is necessary to clarify the concept of transgenesis and appraise the technical possibilities and many risks that are involved in its effective use. The main reason for attempting trans- genesis is to enable a greater number of people—and especially the disadvantaged by a poor genetic makeup—to live healthier and happier lives. A person's capacity to achieve self-realisation depends in part on their power to act upon reality, and transgenesis could be a powerful tool for doing so. 2 The Concept of Transgenesis A central development in medicine and biology over the last 30 years relates to the concept of transgenesis and its ultimate product: the genetically modified organism (GMO). Defining transgenesis has been sometimes complicated by the popular misuse of different terms that are not synonyms but that overlap. For example, transgenesis and genetic engineering have been frequently employed synonymously to refer to a collection of techniques that are used to genetically modify an organism. Nevertheless, as discussed by Shrader-Frechette (2005) and Hug (2008), genetic engineering may be defined either broadly or narrowly. In the broad sense, genetic engineering includes the collection of uncontroversial techniques by which organisms can be selectively improved through the successive crossing of parental beings that contain desirable genetic and phenotypic traits; this approach is popularly known as selective breeding. In the narrow sense, however, genetic engineering refers to the horizontal transfer of DNA fragments or genes from one organism to another, thereby altering the genetic makeup of the second organism. Whereas the first definition does not fit the concept of transgenesis, the latter definition does. The term horizontal gene transfer (HGT), or lateral gene transfer, has also been used as a synonym of trans- genesis. As defined by Keeling and Palmer (2008), HGT refers to the movement of genetic information from one organism to another independently of phylogenetic relatedness. In contrast to vertical gene transfer, in which genetic characteristics are transferred to the next generation through processes of viable reproduction, HGT is mating-independent and may affect organisms in a single generation. In this sense, the concepts of HGT and transgenesis overlap almost completely. Nonetheless, we propose a conceptual differentiation between the two terms, using “transgenesis” in 1 Science fiction classics such as “The Fly”, “The Island of Dr. Moureau” and “Frankenstein” are probably the greatest source of transgenesis-related fear (cf. Brem and Anijar 2003; Karpowicz 2003). It is very unlikely that transgenesis will cause severe morphological changes (cf. Powell and Buchanan 2011: 64). F.G. da Fonseca et al. the context of the biotechnological application of HGT with the purpose of the intentional and focused genetic alteration of a given organism. The biotechnological application of HGT to generate GMOs has met considerable resistance from the general public. This resistance has been especially acute when GMOs are food-related, which has led to continuous and sometimes passionate debates. Many types of plants and some livestock are currently being genetically modified for several reasons. As enumerated by Uzogara (2000), these include better nutritive content, resistance to adverse factors such as disease, pests and bad weather, faster growth and longer shelf life. Advocates of this technology argue that the potential for increased productivity from GMO crops may actually help to solve challenges of world agriculture and provide food for an ever-growing human popu- lation. Moreover, the improvement and simplification of transgenic techniques have led to possibilities in which plants can be tailored to provide and deliver not only nutrition, but also therapeutic components and molecules that are focused on health improvement. Opponents of transgenic foods, however, express fear that the growing presence of GMOsmay result in alterations to the nutritional quality of food, potential toxicity, potential allergenicity and carcinogenicity from the consumption of GMO foods, increased antibiotic-resistance dis- persion, ecological disturbances and the unintended transfer of genes to wild plants. Supporters of GMO production and consumption argue that opposition to transgenic foods is politically driven and is not based on sound scientific facts. Aside from a few controversial studies, there are no definitive scientific indications to deem GMO foods as harmful either to humans or to the environment (Uzogara 2000; Wu 2004; EFSA 2008; Raven 2010). In analysing public resistance to genetically mod- ified foods, Wu concluded that public wariness may result from the fact that con- sumers rarely perceive the benefits that GMO crops could deliver, instead focusing disproportionately on the potential risks associated with such technologies. Although many of the potential risks that are associated with growing and/or consuming GMO foods have been scientifically and independently disproven, the general public remains unaware that the popular media frequently emphasises potential risk rather than the repudiation of alleged risk (Pinstrup-Andersen and Schioler 2000). Ironically,resistance to transgenic drugs is much less intense if not non-existent. As an example, almost all antibiotics that are currently being produced by pharma- ceutical companies are transgenically obtained. Since the 1980s, all human insulin, growth hormones and various blood clotting factors have been biotechnologically produced—made by microorganisms that were genetically modified to express the factors that they produce (Walgate 1981; Toole et al. 1984; Akinci et al. 2010). Today more than 250 biotechnology health care products, vaccines and diagnostic tools produced by genetically modified microorganisms and plants exist; many are being used by patients on a daily basis (BIO 2010). In 2006, the European Commission approved the first mass-produced drug generated by a transgenic animal: a recombi- nant human antithrombin, an anticlotting protein that is secreted into the milk of transgenic goats. Similarly, the US Food and Drug Administration (FDA) has ap- proved the commercialization of a recombinant human C1 inhibitor, a drug used to treat hereditary angioedema, produced by transgenic rabbits (Choi 2006). While many people purchase food only when the company label states that no transgenic components are included, the same does not apply to medicinal purchases, although the word “recombinant” is obligatorily present on the drug information label. Human Transgenesis: Technical Possibilities and Moral Challenges Uzogara (2000) noted that religious and cultural concerns are frequently associated with the opposition to GMOs, and even when these aspects are not clearly present, the simple and crude fear of the novel or the unknown accounts for the public resistance to transgenic organisms. GMO critics have asked the following question: “Should scientists be allowed to cross nature's boundaries by cloning microorganisms, plants, animals, livestock, and possibly humans?” (Woodard and Underwood 1997). Answers given to this question often reveal a basic fear motivating a general aversion to transgenesis: one associated with the taboo against “unnatural” human genetic manipulation. 2.1 Transgenesis in Prokaryotes As described above, HGT and transgenesis involve the mating-independent transfer of genetic material between phylogenetically diverse organisms. Although trans- genesis is referred to as a biotechnological approach to HGT, these two phenomena are identical from a purely mechanistic, molecular point of view. HGT has been recognised as a major force driving genomic evolution (Andam et al. 2010). However, its importance to the evolution of eukaryotic organisms is frequently overshadowed by the much higher prevalence of gene transfer in bacteria (Koonin et al. 2001). Recent studies have suggested that HGT is a common and relevant feature in the evolution of all living organisms, including humans. HGT was first described during an outbreak of dysentery in Japan. The disease was caused by bacteria of the genus Shigella, and scientists were astonished by the rapidness with which antibiotic resistance emerged. It turned out that resistance genes were being transmitted laterally among members of the bacterial population (Akiba et al. 1960). Even so, it was only with the advent of comparative genomic studies that biologists recognised the full extent and impact of HGT in prokaryotes, which caused bacterial evolution to depart from the traditional tree-like phylogenetic structure and form instead a web-like evolutionary history (Doolittle and Bapteste 2007). Bacteria and other related organisms are quite promiscuous in terms of their ability to absorb and integrate foreign DNA into their own genomic repertoire. This is accomplished using an array of different strategies that include (inter alia) taking up DNA molecules that are soluble in their environment, exchanging DNA mobile elements called plasmids through specialised tubules (in a process known as conju- gation), and using viruses as vectors to exchange DNA pieces among infected bacteria (Thomas and Nielsen 2005). Based on the speed by which prokaryotes are able to laterally transfer genes, the impact of HGT on bacterial evolution becomes quite clear. In fact, key events in the geological and biological history of our planet are intrinsically linked to bacterial evolution and consequently to HGT as a major evolutionary mechanism. The appear- ance of photosynthesis and photosynthetic organisms, for instance, radically shaped life on Earth by increasing the global distribution of available atmospheric oxygen, thereby allowing for the development of larger, more complex forms of life. The first photosynthetic organisms were bacteria, and the distribution of genes related to photosynthetic processes among diverse groups within the bacterial domain is a result of the combination between vertical inheritance and lateral gene transfer events (Hohmann-Marriott and Blankenship 2011). F.G. da Fonseca et al. 2.2 Transgenesis in Eukaryotes When compared to gene transfer in bacteria, HGT in more complex organisms is substantially less frequent. The chief reason relates to the segregation of reproductive cells (germ cells) from somatic cells in most multi-cellular eukaryotes. To be trans- mitted from parents to offspring and potentially become fixed within a population, a foreign gene would have to be inserted into the genome of a germ cell, a much rarer event as compared to gene insertion into somatic cells. Although the segregated germline is a strong limitation to HGT in animals, it is certainly not an absolute one. Indeed, cases of HGT in eukaryotes are being described at an increasing rate and may account for many adaptively significant traits (Keeling 2009). The question here is: how could foreign DNA be transported laterally among diverse complex eukaryotic organisms? Current studies have indicated that the eukaryote genome is littered with non-coding pieces of DNA termed transposable elements (TEs) or transposons. TEs are discrete pieces of DNA that possess the ability to move from one locus to another in the genome and frequently duplicate themselves in the process (Schaack et al. 2010). Not only can TEs integrate within the “host” genome, but they can also jump to other genomes to generate HGT events, as first demonstrated in fruit flies (Daniels et al. 1990). The inherent ability of TEs to mobilise and integrate into various genomes suggests that they are perfectly prone to HGT, or in this case, horizontal transposon transfer. The exact mechanisms by which TEs can be transported between organisms are not completely known, but the idea of parasites working as vectors for these mobile genetic elements has been proposed (cf. Gilbert et al. 2010). Eukaryotes can be infected by a multitude of parasites that invade different hosts and eventually carry TEs with them. In this respect, viruses have been considered potent HGT vectors because of their ability to transduce and recombine host DNA and because of their access to eukaryotic cells, including germline cells. A powerful and illustrative example of how viruses could bridge HGT events was presented by the work of Yoshiyama et al. (2001). These authors reported the presence of a specific transposable element in the genomes of the parasitoid braconid wasp and its lepidopteran host, in which the wasp's eggs are deposited and develop. In this case, a type of virus termed Polydnavirus seemed to transfer the mobile genetic element between the two insect species. These viruses have established a symbiotic relationship with the braconid parasitoid wasp to suppress the immune response of their lepidopteran hosts and allow the undisturbed development of the wasp's eggs. The Polydnavirus resides in the wasp's genome as an integrated proviral DNA. In the ovaries, the viral DNA is able to direct the production of new virus particles that are injected into the lepidopteran host with the parasitoid eggs. Thus, a TE present in the viral genome could be transported from the wasp to the butterfly to create theopportunity for an HGT event. Like the Polydnavirus, viruses with genomes that are also able to integrate into the genomes of higher vertebrates, including humans, are known. The most notorious viruses that are capable of integrating into the genomes of vertebrates are the retroviruses. Members of the Retroviridae virus family present RNA genomes that are used as templates to generate proviral DNA. This is accomplished by a virus- coded enzyme, reverse transcriptase. Once the proviral DNA is generated, it is able to integrate into the host genome, persist indefinitely within the cell nucleus, and Human Transgenesis: Technical Possibilities and Moral Challenges generate new virus particles. Such a virus strategy creates a striking opportunity for an HGT event to take place. Indications of ancient retroviral activity in the human genome are given by the existence of genetic elements termed human endogenous retroviruses (HERVs). These elements are remnants of retroviral infections that occurred more than 25 Ma ago in mammalian cells at the birth of the primate lineage. During these ancient infections, proviral DNA became permanently integrated into the genome of germline cells that were passed from generation to generation as a part of the host genome (Belshaw et al. 2004). 2.3 Transgenesis in Humans In comparison to what is known from experimenting with the genetic manipulation of other organisms, there is very little scientific indication of what would be the impact of biotechnological transgenesis in humans, either individually or as a species. Because this hypothesis cannot currently be openly and comprehensively tested, one could look to the past and ask the question: has transgenesis ever occurred in man? The answer would be: yes, and very successfully. When the human genome was finally sequenced, it was verified that HERVs, also termed LTR retrotransposons (Cordaux and Batzer 2009), comprise nearly 8 % of human DNA. Combined with non-LTR retrotransposons and regular DNA trans- posons, these mobile elements account for an astonishing 50 % of the human genome (Venter et al. 2001). As a general concept, retrotransposons are genetic elements that can jump from one locus to another within the genome or among different genomes. Unlike regular transposons, retrotransposons are able to spread through a “copy-and- paste” mechanism by which the original TE copy is not excised from its original locus. Instead, it works as a template to generate an RNA copy of itself. Then, a retrotransposon-encoded reverse transcriptase is used to generate, from the RNA, a new DNA copy that can integrate into another locus or into another genome (Faulkner 2011). Non-LTR transposons are the most abundant of all TEs in the human genome and occupy about one third of the total genomic size. We still lack evidence to suggest how these TEs first appeared in the genome of man; some types of retrotransposons are very old with evidence of ongoing activity, dating back to approximately 160 Ma (Lander et al. 2001). At any rate, it is likely that at least some of these elements were horizontally transferred to the genomes of human ancestors. This transfer has already been demonstrated to have happened in many other mam- malian species, such as in bats of the vespertilionid lineage, murine rodents, lemurs, squirrel monkeys and opossums (Schaack et al. 2010). For many years, the amount of apparently non-functional DNA sequences within the human genome that correspond to TEs has puzzled scientists. Current studies have indicated that these movable elements are far from being non-functional. Retrotransposon activity yields specific genetic diversity that underlies phenotypic variation mostly by generating insertional mutagenesis and structural changes in the DNA. According to Schaack et al. (2010), when exchanged among different species via HGT, transposons can trigger a series of events that actively shape the genomic architecture of the organism and give rise to biological innovation. Indeed, these TE- induced variations account for much of the inter-individual genomic diversity that is observed among humans (Konkel and Batzer 2010). Such intense mutagenic activity F.G. da Fonseca et al. may eventually present deleterious results, including those that have been demon- strated by a number of genetically transmitted diseases that are linked to retrotrans- poson activity (Faulkner 2011). Still, the genetic variations that are provided by TEs have been considered to be essential mechanisms of genomic evolution. A good example of such mechanism is the inactivation of a gene, which encodes for a specific hydroxylase enzyme, after the evolutionary divergence between the Homo (man) and Pan (chimpanzee) lineages. This particular gene inactivation, caused by the simple insertion of a retrotransposon, is believed to have influenced the expansion of the human brain and the appearance of phenotypic and cognitive traits that are unique to the human species (Chou et al. 2002). We still lack clear scientific evidence of a recent HGT event between the human genome and that of any other species. However, as reported by Schaack et al. (2010), this lack could be due to the technical fact that only approximately 1,000 full eukaryotic genomes from an estimated 1.5 million species have been sequenced. Because the discovery of HGT events is based on comparisons between the different available genomes, such restricted sampling may be impairing our ability to find evidence of recent lateral gene transfers to humans. However, this phenomenon has been unequivocally demonstrated in many other mammals, including new world primates, which are closely related to the hominid lineage. If one considers the evolution of the human species not as a pinpoint event in time, but rather as a cumulative chain of events that involved many different but related ancestors, then the influence of HGT contributing to the human genome becomes absolutely unde- niable. Transgenesis in humans has already occurred. 2.4 The Feasibility of Transgenic Treatments in Humans: Gene Therapy We have established that “natural” transgenesis is not new to humans. But how close are we to harnessing deliberately the therapeutic potential of transgenesis? Although there are no failure-proof or adverse effect-free techniques for carrying out trans- genesis in humans, methods for the stable introduction of exogenous DNA into the genome of humans have been known for many years. The most feasible method utilises retroviral vectors that carry exogenous genes. As mentioned before, these viruses are able to integrate their own proviral DNA into the genome of the host cell, and thus they are also capable of inserting any other piece of foreign DNA. This principle was experimentally demonstrated in 1981 for the first time when Wei et al. (1981) inserted a herpes virus gene into the genome of a mouse using a retroviral vector. Since then, hundreds of different experimental studies evaluating efficient therapeutic gene delivery into mammalian cells by retroviral vectors have been conducted, and more than 250 human gene therapy clinical trials employing retroviral vectors have been initiated in the last decade (Cockrell and Kafri 2007). Expectations were high when a group of independent researchers announced in the mid-2000s the successful correction of three hereditary hematopoietic disorders in humans with the use of simple retroviral-based vectors (Cavazzana-Calvo et al. 2000; Aiuti et al. 2002; Ott et al. 2006). However, the euphoria turned into disap- pointment when three patients from one of the clinical trials developed leukaemia as a result of mutagenesis that was caused by the uncontrolled insertion of the retroviral vectors into the patients' DNA (Check 2005). Safety concerns and the inability of Human Transgenesis: Technical Possibilities and Moral Challenges simple retroviruses to insert their proviral DNA into the genome of cells that are not prone to divide blocked all furtherdevelopments of the retroviral gene delivery systems. This temporary moratorium ended when a unique group of retroviruses, the lentiviruses, started to be evaluated as safer and more efficient vectors than the other retroviral vectors being employed. Lentiviruses have the capacity to efficiently transduce non-dividing cells, including hematopoietic stem cells and cells from the central nervous system, liver, eye, heart and pancreas (Wiznerowicz and Trono 2005). Moreover, specific genetic modifications of lentiviral vectors have rendered them able to mediate long-term transgene expression in vivo, whereas the unwanted insertion of the lentivirus genome into the host DNA has been considerably diminished, although not completely abolished (Cockrell and Kafri 2007). Successful pre-clinical studies using these new vectors to treat genetic disorders rapidly appeared and provided excellent outcomes in animal model studies of Alzheimer's, Parkinson's and Huntington's diseases (Wong et al. 2006; Wakeman et al. 2011); immunodefi- ciencies and various haemoglobin disorders (Levasseur et al. 2003; Mostoslavsky et al. 2006). Technical innovations in transgenesis were also accompanied by regulatory improve- ments, which were developed by special committees formed to evaluate and control the human clinical trials involved in gene therapy and gene delivery methods. An example of such a regulatory body is the Center for Biologics Evaluation and Research, a branch of the US FDA that has set guidelines for the long-term follow-up of patients enrolled in human gene transfer studies (Nyberg et al. 2004). With all favourable conditions now in place, the therapeutic applications of lentiviral vectors are beginning to transition from pre-clinical animal models to corrective therapy in humans. Importantly, the comeback of the gene transfer approach to treat human genetic disorders after the iconic failures of a decade ago have prompted research with other viral vectors, including adeno-associated viral vectors, which have been used to treat heart con- ditions in a number of current human clinical trials (Kawase 2011). Thus, therapeutic gene transfer techniques that employ viral vectors and other emerging methods are not simply a technological promise; they are an actual reality. Human gene transfer can be used to potentially treat many, if not most, incurable, infectious and genetic maladies. Going even further, different genetic traits can also be introduced into the human genome with objectives that are not only therapeutic but also geared towards the enhancement of normal human capacities. It would not be much of an exaggeration to say that limitations for the use of gene transfer in humans are becoming less technical and more ethical in nature. 3 Morals and the Pursuit of Transgenic Enhancements in Human Beings 3.1 “Human Nature” is Transgenic In the Western World, humans have sought to establish themselves as a separate class of beings in the physical and natural world, distinguished from other beings by an array of unique and, more often than not, God-given attributes that make them special and superior to other life forms (cf. Mirandola 1994). “Human nature” is a key concept through which this idea has been communicated. This idea is deeply rooted F.G. da Fonseca et al. in the theological doctrine of Christianity, which in the middle ages defined man as an “individual substance of rational nature”2 sharing some of God's divinity by being created in His image—a by-product of perfection in the form of a complete and immutable essence. However, the aforementioned developments in the fields of genetic engineering and molecular biology have helped to demolish the view that human nature is a static entity or that the DNA could be likened to an “essence” of life. Humans are highly transgenic. Transgenesis is not simply an accidental factor in the development of the human species but a fundamental force that drives biological evolution, including that of humans. This conclusion should be enough to brush aside arguments claiming that the use of gene therapy for purposes of treatment/enhancement could alter or modify human nature. Since transgenic interventions in the genome would not be qualita- tively different than naturally occurring events, such interventions would not alter human nature more than natural transgenesis already does. If transgenesis occurs as a non-intentional process that drives biological novelty and adaptation, why not use it for human purposes? Some could still argue that while intentional transgenesis could be attempted for the purposes of restoring normal encoding DNA in diseased genomes, artificially pushing for biological innovation could be extremely dangerous because it represents a step beyond natural design into a realm of biology and biological risk that is largely unknown. However, the supposed gap between these two types of interventions is illusory. Notably, the technical means for achieving both goals are largely the same, and thus, so are the risks. The leap into the unknown is not that much of risk either because scientists are likely to work on gene sequences that are extensively and exhaustively researched for their properties and effects as much as they are for treatment and enhancement. This concern could be addressed more directly by saying that any gene therapy intervention in humans should follow strict risk assessment protocols, and no clinical trial should be conducted without sufficient evidence that the intervention might prove to be beneficial and that the risks are acceptable for scientists, the subjects and society. Nature is not an intentional entity. As such, nature is not wise or beneficent in controlling transgenesis.3 Transgenesis has occurred as a matter of chance in organ- isms that are prone to its occurrence, and has been incorporated as a populational genomic feature in situations in which transgenic alterations increased the propensity of organisms to survive and reproduce in their environments. On the other hand, there are good reasons to learn how and why non-intentional transgenesis has helped organisms survive, and what sort of phenotypical traits have successfully emerged from it. Pursuing this knowledge should be an imperative. 3.2 Making Transgenic Persons The risks associated with genetic engineering are many: accidental infections with viral vectors, the development of cancerous cell growths and the creation of docile, or 3 In fact, nature’s wisdom at large is a debatable proposition or ethical claim (cf. Bostrom and Sandberg 2009; Powell and Buchanan 2011). 2 [N]aturae rationabilis individua substantia (Boecio 2005: 168). Human Transgenesis: Technical Possibilities and Moral Challenges less autonomous sentient beings, etc. Such concerns would seem to warrant against transgenic interventions in human embryos. However, it should be pointed out that designing human beings is not a new thing, and that the risks presented by genetic engineering are not higher or more daunting than the risks involved in other existing forms of manipulating human persons (i.e., educational processes, nootropic nutri- tion, pharmaceutical interventions, surgical interventions, stimulus control, cognitive therapy, etc.). As Sagoff (2005: 72) reported, there is no reason to believe in “genetic exception- alism,” the idea that genes serve a larger or more essential role in determining one's physical appearance or personality than other environmental factors. The genome has a (limited) scope of influence and is only one among many factors. In this sense, genetic engineering techniques are an effective way to manipulate the “gene factor” as merely another addition to the large array of manipulation tools that we already possess. Thus, because what can be changed by means of genetic engineering is not at all different from what can be altered by other tools, transgenic interventions present only a quantitative change to the existing framework for changing humanbeings, not a qualitative one.4 The problem does not lie in the tool itself, but in what use people will make of it. 4 Conclusion The biological and social possibilities that transgenic interventions may bring about are further evidence that reality is complex, dynamic and uncertain: The deeper our grasp of reality, the more we realise that there are no essences to be found, no underlying intentionality to be followed, and no holiness to be respected. Even as the concept of human nature dissolves into nothingness, the uniqueness and capacity of human agency is increased. Taking control of and responsibility for our evolu- tionary future means recognising and assessing genuine risks, not retreating behind obsolete notions concerning the essentialistic qualities of the human genome or the purported wisdom of the evolutionary process. It is time that we recognise trans- genesis as an eminently natural process, one that plays an important role in the development and evolution of all species, including Homo sapiens. Acknowledgements Brunello Stancioli acknowledges the support of CAPES – as a beneficiary of one of its scholarships for post-doctoral studies abroad – for his work on this article. References Aiuti, A., et al. (2002). Correction of ADA-SCID by stem cell gene therapy combined with nonmyeloa- blative conditioning. Science, 296, 2410–2413. Akiba, T., et al. (1960). On the mechanism of the development of multiple-drug-resistant clones of Shigella. 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