SILVA, Poliane Cardoso da. MORAIS, Lauandecy Maria Domingas Costa de. LEAL, Kamila Soares. The repercussions of genetic editing in humans using the “CRISPR-CAS9” technique. Revista Científica Multidisciplinar Núcleo do Conhecimento. Year 06, Ed. 09, Vol. 05, pp. 85-107. September 2021. ISSN: 2448-0959, Access link: https://www.nucleodoconhecimento.com.br/law/crispr-cas9-technique
Genetic editing through the CRISPR-Cas9 system has enabled major advances in the field of genetic engineering, including the ability to genetically modify human embryos with reproductive potential, which has recently occurred in China. Thus, many controversies arise on the subject that raises scientific, ethical and legal dilemmas, a problem that led the present study with the following question: What are the main scientific, ethical and legal repercussions arising from genetic editing in humans through the application of the CRISPR-Cas9 technique? Thus, the objective was to investigate such impacts in order to weave the appropriate reflections on the subject in the current scenario, considering the protection of genetic heritage due to the principle of dignity of the human person. We also sought to approach these aspects in an interdisciplinary way, in order to raise the law according to anthropocentric perspectives. To carry out the study, we used integrative and documentary theoretical-bibliographic research, operationalized through the search for academic papers in national and international indexers, official sites of consultation of legislation, as well as updated books, available in the physical and digital environment. It was obtained that the CRISPR-Cas9 system is extremely promising considering its applications for gene therapy, however, the application of gene editing in human reproductive cells is in the midst of scientific uncertainties with unexpected results, such as mosaicism and random mutations; in relation to normative issues, there is national and international protection to genetic heritage with regard to human embryonic cells, because human DNA is considered as an inherent good to humanity, and no change is passed on to future generations; regarding the ethical implications, the modification of the natural composition of the human being means the breaking of a limit that hurts the principle of self-determination of the individual, while allowing to glimpse eugenicpractices and increase social segregation. It is concluded that the possibilities brought by genetic editing through the explored technique are inevitable and, therefore, it is up to the legal system to seek to update itself on its prediction, such updates should, above all, consider the ethical principles that guide bioethics and biolaw. It is emphasized that more conclusive research should guide such interventions.
Keywords: Genetic editing, Repercussions, Dignity of the human person.
The discovery of more practical means for genetic editing in humans caused great fanfare in the scientific environment, mainly due to the announcement of the birth of the first genetically modified humans, a fact that occurred in China, through the use of the technique “CRISPR-Cas9”- Clustered Regulary Interepaced Short Palindro Repeatmics, the term refers to the fragments of the DNA ribbon.
Genetic editing from the CRISPR-Cas9 technique comes from the application of the functions performed by true observable machinery at the molecular level, where dna segments are modified, according to Amabis and Martho (2010) DNA is the structure that carries all the hereditary information of single or pluricellular living organisms, its double-helix structure is composed of thousands of nucleotides joined sequentially whose follow-ups form the genes , places that indicate the expression of the characteristics of each individual, for example, the color of the eyes, shape of the face, even may have anomalies that are expressed in hereditary diseases.
Thus, mastering genetic manipulation means controlling the expression of the genotype and phenotype of organisms, that is, their genetic composition and its externalization. It is substantial to report that the first results with CRISPR-Cas9 show promise in view of the possibilities brought by gene therapy (ORMON et al., 2017).
However, it is necessary to highlight the divergences present in the scientific environment, because there is no consensus regarding such manipulations, since some studies have indicated side effects capable of resulting in losses such as harmful mutations in other genes, the appearance of cancers and other unmeasured changes, adding to this the fact that the definitive changes in DNA impact future generations in their biological and social dimensions (CLEMENTE, 2020).
In the current conjuncture, scientific uncertainties lead to ethical and legal dilemmas concerning the theme, in view of the principles that guide bioethics and biolaw. Regarding national legislation, there is the regulation of genetic engineering activities, through the Biosafety Law (No. 11.105/2005), this device seals the practices of genetic interventions involving germ cells and human embryos (BRASIL, 2005). Similarly, there is international protection to genetic heritage, through devices aimed at universal protection of genetic material as a fundamental unit belonging to human beings (UNESCO, 1997).
In this context, the present study aimed to investigate in a way the main scientific, ethical and legal repercussions of genetic editing in humans through the CRISPR-Cas9 technique, in order to weave due reflections on the subject in the current scenario, considering the protection of genetic heritage due to the principle of dignity of the human person. We also sought to approach these aspects in an interdisciplinary way, in order to raise the law according to anthropocentric perspectives.
The present study is of great importance to the academic and social environment because it seeks greater knowledge about the nuances involved in a controversial theme, currently of great repercussion for biolaw and related areas, as is proper to a multidisciplinary theme. It is a subject involving human and fundamental rights, such as the dignity of the human person in the face of technological innovations characterized by mechanisms increasingly present in the postmodern world and which, therefore, make up the generating facts of current and future law, whose dynamism requires maximum attention and constant deliberation.
To carry out the study, we used integrative and documentary theoretical-bibliographic research, operationalized through the search for academic papers in national and international indexers, official sites of consultation of legislation, as well as updated books, available in the physical and digital environment.
This work follows an organization presenting as results and discussions the following thematic axes: genetic editing; CRISPR-Cas9 technique; protection of human genetic heritage; scientific limitations of the CRISPR-Cas9 technique in humans and the ethical implications surrounding the said technique, finally the last section brings the general considerations as a product of the investigations carried out.
2.1 THE GENETIC EDITION
Genetic engineering enables the editing of human genetic material through the transfer of genetic sequences that will be recombined with other DNA segments, an activity that requires proper control and regulation so that risks to human life are avoided, as the principle of human dignity is respected (MALUF, 2020, p. 59).
The practices of modification of the organism through genomic editing imply an improvement of the same, giving it desirable characteristics, as stated by Scarmanhã; Silva and Garé:
A engenharia genética realiza processos de manipulações genéticas, objetivando que elementos sejam duplicados, transferidos ou mesmo isolados dos genes originais. Assim, com estes procedimentos, é possível obter seres com genética melhorada com qualidade e aprimoramento de funções (SCARMANHÃ; SILVA; GARÉ, 2019, p. 05).
In this dimension, the applications of genetic engineering can be carried out in any animal or human organism, to which Clemente (2020) ensures, as far as the applications of genetic editing are initially restricted to somatic cells, i.e. non-germ cells, which are present in most of the human body and differ and specialize in various tissues and organs, while gametic cells are essential for the reproduction of a new being. In summary, changes in germ cells can be passed on to future generations, on the contrary, changes in somatic cells remain only in the individuals who have them in their composition.
Given these possibilities, the dynamic character of the sciences that always tends to advances, with genetic engineering did not occur different, says Beriam (2017) that still in 2015 began to intensify the debates about the genetic alteration of human germ cells, or genetic editing of eggs, sperm and embryos (fertilized eggs), thus, there was the possibility of manipulating the genetic material of human embryos.
As for genetic editing in humans, the homeland legislation tends to prohibit related practices, through the Biosafety Law, which establishes standards for the use of genetic engineering techniques and the release of Genetically Modified Organisms – GMOs in the environment (BRASIL, 2005).
There is a prohibition of genetic alteration in embryonic or germ cells of human beings, by reading Article 8 of the aforementioned device, other prohibitions concerning manipulation involving germ cells are noted:
Art. 6º Fica proibido:
I – Implementação de projeto relativo a OGM sem a manutenção de registro de seu acompanhamento individual;
II – Engenharia genética em organismo vivo ou o manejo in vitro de ADN/ARN natural ou recombinante, realizado em desacordo com as normas previstas nesta Lei;
III – engenharia genética em célula germinal humana, zigoto humano e embrião humano;
IV – Clonagem humana; (…) (BRASIL, 2005).
It is noteworthy that the aforementioned law considers the application of genetic engineering in the editing of human germ cells a crime, providing in article 24 that such conduct, as well as any act of violation of human genetic material in vivo that does not aim at the reversal of genetic defects and is outside the legal dictates will result in the detention penalty of 1 (one) to 3 (three) years and fine, human cloning and use of human embryos are also penalized in disagreement with legal forecasts:
Art. 24. Utilizar embrião humano em desacordo com o que dispõe o art. 5º desta Lei:
Pena – detenção, de 1 (um) a 3 (três) anos, e multa.
Art. 25. Praticar engenharia genética em célula germinal humana, zigoto humano ou embrião humano:
Pena – reclusão, de 1 (um) a 4 (quatro) anos, e multa.
Art. 26. Realizar clonagem humana:
Pena – reclusão, de 2 (dois) a 5 (cinco) anos, e multa.
Art. 27. Liberar ou descartar OGM no meio ambiente, em desacordo com as normas estabelecidas pela CTNBio e pelos órgãos e entidades de registro e fiscalização:
Pena – reclusão, de 1 (um) a 4 (quatro) anos, e multa. (BRASIL, 2005).
It remains clarified the position of the law regulating the activities linked to genetic alteration of organisms, this is allowed in other non-human living beings and in non-embryonic or reproductive human cells. On the other hand, modern biotechnology evolves more controversial and revolutionary genetic manipulation procedures (REIS; OLIVEIRA, 2019).
Also according to the authors, among the revolutionary techniques resulting from biotechnological innovations, more specifically in the field of genetic engineering stands out the gene editing technique called CRISPR-Cas9, which allows to replace segments within the DNA tape correcting possible errors or genetic flaws by inserting desired or more beneficial characteristics. This possibility awakens to a reflection on the risks arising from the manipulation of the human being following his interests, such as the possibility of eugenic practices (REIS; OLIVEIRA, 2019).
2.2 THE CRISPR-CAS-9 TECHNIQUE
According to Sander and Joung (2014) the CRISPR-Cas9 system emerged from molecular engineering of the immune system of bacteria, this enables the editing of any gene through dna fragmentation by a restriction enzyme called “Cas9”, which is directed by a transporter RNA, and has the ability to pair with sequences of specific nitrogen bases.
Corroborating the same understanding above, Boel et al., (2016) compared the technique to a text editor, starting from the point that DNA is written code, and as any other can present errors in its structure, as well as the tools for identifying written errors, the technique recognizes specific nucleotide sequences in the target DNA, as well as uses clipping media to select them.Figure 3 illustrates how the genetic editing mechanism takes place through the CRISPR-Cas9 system.
Figure 3 – CRISPR System – Cas9
In this context Clemente refers to two main moments in the editing mechanism mentioned here, namely, the stage of recognition and cleavage where the dna molecule is cut, followed by the repair phase of the dna, as well:
O processo de edição divide-se em duas etapas, sendo a primeira relacionada ao reconhecimento e clivagem da molécula de DNA e, a segunda, destinada ao reparo da mesma. Uma vez seccionados, os nucleotídeos são acionados mecanismo celulares endógenos, naturais de reparação do DNA. O processo de edição utiliza-se então, desses recursos, para promover modificações pretendidas. Assim, o reparo pode ocorrer por ligação das extremidades não homólogas (mecanismo útil quando se pretende silenciar a ação dos genes) ou também, por reparo dirigido por moldes. Nessa situação, é possível inserir, nas moléculas, juntamente com a ferramenta de edição, moldes de DNA externo. Assim, pode-se fornecer moldes externos contendo genes selecionados, ao novo seguimento de DNA a ser formado no local da clivagem (CLEMENTE, 2020, p. 15).
It is understood that the cell has internal repair mechanisms that are activated through the action of the CRISPR-Cas9 system, where it uses such means to provoke changes of interest, these changes can occur from a mold inserted in the process or by the use of the ends already present in the DNA tape.
The technique discussed here has been promising due to its simplicity, speed and efficiency in genetic manipulation, as Clemente (2020) states, the advantages of this technique represent a real revolution in health treatments, especially in relation to serious diseases of hereditary origin, which are often incurable. Therefore, a positive expectation is generated in relation to the new therapeutic alternatives.
The applications of gene editing in humans offer many advantages from more basic to more advanced research, enabling several improvements for humans, among the innovations can be cited: the understanding of cell differentiation in the process of development of the human body, the functioning of particular genes still in the embryonic phase of the organism, understanding about diseases of genetic origin, providing the production of specific drugs such pathologies, advances in gene therapy (cancer treatment), among other mechanisms that are still in the study phase (CLEMENTE 2020).
Also in relation to applications, it is worth emphasizing on the genetic editing of newborn children conditions of hereditary congenital malformation, at least 6% of newborn children present serious genetic problems, through the mechanism CRISPR-Cas9 identifies the dna segments that are responsible for causes such pathologies, so it is possible to seek preventive treatments (CLEMENTE, 2020).
The benefits still apply to the physiology of the immune system. Many genes are directly related to the resistance of some individuals to infection-causing pathogens, the identification of these sites in the genome means extending their advantages to other organisms and promoting effective immunization. It is emphasized that such procedures are already a reality (ORMOND et al., 2017).
2.3 THE PROTECTION OF GENETIC HERITAGE
Biotechnological advances are increasing and are gaining more and more space, which infers the need to promote effective protection to the human genome, aiming at the preservation of future generations (NAVES; GOIATÁ, 2017).
Such protection falls on complex themes, since many conflicts arise, from economic interests to philosophical and religious ethical discussions, but the broad human capacity to apply technological means for the modification of biological systems requires proper control based on “regulation and establishment of concrete measures for preservation through the proper and conscious use of biological resources” (NASCIMENTO; BRITO, 2021, p. 5).
Genetic heritage corresponds to any “information of genetic origin of plant, animal, microbial or other species, including substances derived from the metabolism of these living beings” (BRASIL, 2015), this concept was adopted by law 13,123 of May 2015, which regulates the constitutional provision on the preservation of the integrity of genetic heritage, as well as measures to protect and access genetic heritage, established in the Convention on Biological Diversity that was unilaterally proposed for nations to sign during the United Nations Conference on Environment and Development in 1992.
Thus, genetic heritage is any hereditary unit present in single or pluricellular organisms, as well as substances resulting from their metabolic activities. Therefore, their protection falls on the animal genes, plants of microorganisms, and humans. However, the rights and obligations provided for in the Law on Access to Genetic Heritage do not apply to human material, as described in Article 4.
Thus, this rule does not include rules regarding access to human genetic heritage. This is justified by the guidelines and prohibitions brought by the Biosafety Law, whose prohibitions focus on conducts involving alteration of embryonic cells, cloning and any modification of genetic material in vivo in disagreement with current norms (BRASIL, 2005).
It is worth emphasizing on the prohibitions to focus on the modification or manipulation of embryonic cells, that is, reproductive cells, however, there is a gap concerning the application of genetic modification techniques in somatic cells, which through the mitosis process differ to form tissues and other human organs. It is subtly subtly within the standards and regulatory standards they may be subjected to gene alteration processes.
In fact, until a few years there were no regulatory standards in relation to such mechanisms, however the National Health Surveillance Agency – Anvisa, regulated in 2018, through RDC No. 260, the rules for the clinical trial of products of advanced investigational therapies, including gene therapy, according to Anvisa (2018) this has as biological product DNA or recombinant RNA aiming at the modification of genetic expression for the purpose treatment, preventive or diagnostic treatment.”
Therefore, gene therapy performed in non-reproductive human cells has become manipulateable, but the purpose is exclusively medical, a therapy that implies treatment or prevention.
In this context, it is emphasized that the standard regulated such procedures at experimental levels “investigational” being, according to Anvisa itself (2018) “for the purpose of proving safety and efficacy”. However, in 2020 the same agency registered the first gene therapy in Brazil for the treatment of Spinal Muscular Atrophy – AME (NOVARTIS, 2020).
Considering that biotechnological applications permeate among all groups and kingdoms of living organisms, the subject is directed to the protection of human genetic material, which is the object of national protection through the aforementioned safety and international standards through the human rights protection system.
Human rights are envisioned according to their dimensions of protection, in a simple way we speak of first-dimensional rights that protect individual freedoms, second-dimension rights whose protection falls on social rights and the third dimension relating to trans-individual rights, however, a fourth dimension has provided for the rights relating to biotechnology issues, genetic engineering and its ethical-legal implications in spite of the conservation of human life (GORCZEVSKI, 2009).
The fourth generation human rights and their regulation arose due to the new problems arising from technological and scientific advances, which had not been faced until then, however they were perfectly predictable, especially those pertinent to research with the human genome and its manipulation (NETO, 1998).
Thus, anticipating the implications of scientific and technological advances in matters pertaining to genetic manipulation, in 1997 the 29th UNESCO General Conference adopted the document proposed by the International Bioethics Committee, which was conceived as the “Universal Declaration of the Human Genome and Human Rights”.
The Universal Declaration of the Human Genome and Human Rights aimed to emphasize the dignity of the human person in the face of research related to genetic intervention, the rights of individuals undergoing treatment or diagnosis that affect their genome and establish the limits to be observed by the nations that carry out such research. In this context, the letter states that “The human genome underlies the fundamental unity of all members of the human family and also the recognition of its inherent dignity and diversity” (UNESCO, 1997).
Thus, the protection of genetic heritage proposed by Unesco provides for the protection of human individuality, which is in line with the scientific aspects of DNA, since genetic material is universally composed of the same molecular structure and performs the same physiological functions, however, it is a unique and exclusive code for each individual. Even if it carries information from its ascendants, it functions as a text, describing the physical characteristics of each individual. It is what connects the whole human family, while conferring the originality of each person, as a fingerprint.
Thus, the device recognizes the genetic content of each person is a heritage belonging to all humanity, whose diversity must be respected and recognized, otherwise it violates the principle of the dignity of the human person, which governs each and every nation based on a democratic regime. In this sense Naves and Goiatá (2017, p. 03) agree that “the protection of human genetic data is the protection of the genetic heritage itself and the continuity of the species in dignified conditions”.
Corroborating, the aforementioned legal provision, it evades any discrimination due to the genetic composition of a given person so that such violation causes injury to human rights and other fundamental freedoms (UNESCO, 1997).
In this dimension, Brazil, in harmony with the predictions of international protection to the genome, the CF/88 magna carta, in Article 225 §1 paragraph II, entrusted the public authorities with the duty to “preserve the diversity and integrity of the country’s genetic heritage and to supervise entities dedicated to the research and manipulation of genetic material” (BRASIL, 1988), the aforementioned legal provision, however, came to be regulated with the edition of the biosafety law, which regulates safety standards and supervisory instruments of activities involving genetically modified organisms – GMOs and their derivatives, and creates the National Biosafety Council – CNBS, as well as restructures the National Technical Commission for Biosafety – CTNBio, on the National Biosafety Policy (PNB ) (BRASIL, 2005).
2.4 LIMITATIONS OF GENETIC EDITING IN HUMANS FROM CRISPR-CAS9 TECHNIQUE
The protection of genetic heritage is very valid for making the proper predictions through the perspectives of biotechnology and genetic engineering, from the most archaic mechanisms of genomic editing to the most modern and effective opened a window for a future of great discoveries and ability to improve life on earth.
However, it should be reflected that such a window is a double-edged sword, as man can use scientific resources to benefit the environment and human health, it is also under his plan the alternative of applying them for economic interests only, without measuring the impacts.
It is still necessary to verify the fact that there is still full control of the operationalization and results of certain techniques, as observed in the case of the use of the CRISPR-Cas9 mechanism.
In this sense, the possibilities arising from biotechnological advances revolutionized the way of considering genes, especially in relation to scientific and economic aspects, given the expansion of studies and the valorization of genetic content, now recognized as a fundamental part for biotechnological advances (NASCIMENTO; BRITO, 2021).
Although the technique of genetic editing from the CRISPR-Cas9 mechanism has proved fast, efficient and economical, the literature reports some limitations, which naturally implies risks, or side effects.
Therefore, in the scientific context from which experiments and studies emerge, there is the presentation of controversial results regarding interventions in relation to genetic material.
It is emphasized that in the scientific field there are two types of controversies, which are internal, arising from inconclusive, incomplete or too complex issues; external ones, related to concerns, value judgments, beliefs, religious, philosophical, cultural or ethical conceptions (HODSON, 2018). This dimension discusses the inconclusive or flawed results, which are related to the uncertainties of scientific experiments, as well as their impacts, specifically in relation to genetic editing in humans.
According to Thompson et al., (2019) some in experiments with embryos submitted to genetic editing occurred what may be called mosaicism that results from an error in cutting the follow-up of interest, such error may result from two possibilities, unsuccessful cutting by nuclease (Cas9 that performs cleavage), or due to incorrect repair of this. The result is the occurrence of at least three types of cells, which are, with genetic material of origin, those modified with mutations and those that have been correctly altered, that is, the organism begins to have a genetic composition containing different sets of DNA.
In this context, this effect is related to a patchwork or mosaic, alluding to “genomic fragmentation” of the organism. It is important to highlight the presence of mutation in cells where repairs did not occur, it is important that most mutations are deleteeria, that is, they lead to congenital deficiencies of genetic origin, such as several syndromes.
It is emphasized that if mosaicism may or may not occur the expression of undesirable genes, however, once present in the composition of the individual, there is the possibility of it being transferred to future generations (CLEMENTE, 2020).
Another factor that requires caution and great care is the possibility of random modifications “off-tarfegt”, are accidental mutations where the enzyme misses the cutting target, occurring by an event not determined in Cas9, which leads to atypical and unintended actions (MARTI-GUITIERREZ et al., 2017).
In front of the exposed Ormond et al. (2017) argue that such mishaps are small in view of the technique’s ability to cure a multitude of diseases, whose negative effects are certain and devastating. And yet, the emergence of unforeseen results is not a rule, since DNA itself is able to withstand a certain level of mutations.
It is infers that genetic manipulations in human DNA have not presented results with one hundred percent certainty about the application of the CRISPR-Cas9 technique, which may result in damage such as harmful mutations in other genes, and other unmeasured changes, since inda science itself does not know the totality of the effects of gene expression.
However, Ormom et al. (2017) assert that in relation to in vitro gene editing should not be the target of obstacles, provided that it is under ethical legal and safety protocols, such as donor authorization and appropriate supervision. It is perfectly appropriate yet, public funding for such research.
As for the continuation of technical applications in human germ lines with reproductive potential, at least four points should be considered, namely, “(a) a convincing medical justification, (b) an evidence base supporting its clinical use, (c) an ethical justification, and (d) a transparent public process for requesting and incorporating contributions from stakeholders” (ORMON et al., 2017, p. 01).
The author concludes that in view of the scientific questions for which no answers have yet been obtained, the editing of genes in the human embryonic lineage with reproductive capacity should not be performed, such practices are completely inadequate (ORMON et al., 2017).
The opposite situation occurred in China in 2015, where a group of researchers under the supervision of scientist Junjiu Huang of Sun Yat-sen University conducted studies on human embryos using the CRISPR-Cas9 technique, aiming to correct a mutation present in the HBB gene, whose function is to encode the beta-globin protein (LIANG et al., 2015).
The most controversial came in 2018 with the announcement of the birth of twins Lulu and Naná, first genetically modified humans, where scientist Jiankui He used the CRISPR-Cas9 mechanism to alter CCR5 genes, make children immune to the HIV virus (CÁRDENAS-KRENZ, 2018).
According to news reports the scientist was condemned by the Chinese justice, when he assumed the genetic programming of another child, so, even without prohibitive rules in relation to genetic editing of humans, but given the social distaste, the researcher was sentenced to 3 years in prison (JUNQUEIRA, 2019).
On such controversies there is no further information, China is an extremely closed nation. Therefore, there are no studies or news of how such children are, nor how the third baby is, whether it survived or presented any anomaly.
2.5 ETHICAL IMPLICATIONS REGARDING GENETIC EDITING IN HUMANS
With regard to ethical implications, the failure/limitations/failures or even the successful application of genomic editing from CRISPR-Cas9, generate repercussions (ORMON et al., 2017). In this scenario, Sandel (2013, p. 84) warns of the inevitable existence of dilemmas and controversies, since there is technological and scientific advances, but the evolution of society does not happen at the same pace.
As for the negative aspects, it is considered between the exposure of individuals to interventions with harmful potential in the face of the uncertainty of such risks overcoming the benefits, as is the case in the case of the editing of human embryos, the effects of which will still be determined (ORMON et al., 2017).
A crucial point in the ethical debate refers to the autonomy of individuals, even in the face of the success of the technique, according to Ormon et al., (2017) such technology has major impacts by generating a genetically modified being without their consent.
At this point, it would be necessary to consider that parents are the most appropriate people to decide on the lives of their children, however it is a controversial subject, because it refers to the genetic composition of someone, an individual being who will express their genotypic characteristics and live with them forever.
In this dimension Hayden (2016), states that parents, including, already exercise immense control over their children, such as the possibility of genetic screening during prenatal care, where it is possible to verify the occurrence of abnormalities in DNA as is the case of trisomy 21 – Down syndrome, and also in relation to the choice of taking or not a pregnancy to the end, as in some countries.
In this context, the number of movements opposed to this control has grown, like those who consider conception itself an immoral act, for bringing to existence someone who has never asked to be born, according to Benatar (2015, p. 60), the main defender of the idea, procreation may seem something innocent, but it is actually very harmful, because a child born is the target of all the ills and terrible things that can happen, although not everyone will suffer great horrors, no one is free from serious harm, the best way to protect a child from the terrible things of life is not to have them.
Added to this is the fact that there are reports of individuals who, even though they have rare and “disadvantageous” genetic conditions such as albinism and nnism, state that they would not like to have their genetic content altered to become normal people (HAYDEN, 2016).
There is also the possibility of intervention by choosing genes that express pathological conditions, as Sandel (2013, p. 86) states, the author reports the case of a couple of deaf women, who through assisted reproduction enabled the conception of a child also deaf, such interest consisted in the defense that deafness would not be a preventative condition of a life like any other. In fact, the child was born with deafness.
There remains a great dilemma regarding the limits of genetic editing for the treatment of conditions considered abnormal by common sense, according to Haydem (2016), many deaf people do not consider their condition as a disease or deficiency, even denying interventions such as implant cocloto and also prevent their children also deaf from being submitted to treatments.
Corroborating, Lamphier et al. (2015) points out that in addition to the risks related to eugenics, there are problems related to possible damage to the human lineage itself, since the alteration of genetic material implies the hereditary transfer of characteristics, it means the irreversible modification of a human being and his descendants.
In addition, Habermas (2016) adds concern to the ethical self-understanding of the species, that is, the subjective and existential aspects of the person who was genetically edited under the judgment of others.
The aforementioned author dedicated himself to raising the questioning and surrounding the violation of the self-determination of individuals, despite the clear certainty that an embryo has no volitional character, it is in full development and will become a being endowed values, longings and inversely, in the words of the same, this eugenic intervention “limits the autonomous configuration of the individual’s life and undermines the fundamentally symmetrical relationships between free and equal people” (HABERMAS, 2016, p. 15).
There is a clear and remarkable conflict in this biotechnological process with the propitious ness of bioethics, among which can be mentioned, the principle of autonomy, according to Maluf (2020, p. 155) is related to the capacity of self-governance of individuals. The interference in the genes of embryos suitable for reproduction would mean, within brazilian ethical and legal limits, the violation of this principle.
Another principle “in the crosshairs” of genetic editing is the very dignity of the human person, for Maluf (2020, p.155) this in harmony with the principle of sacredness, they foresee the protection of human life in all its dimension.
In this tuning point, it is important to discuss the controversy surrounding the emergence of personality, which according to Venosa (2007, p. 230) in the Brazilian legal system is useful to raise the rights of each individual, on this theme radiate divergences around the unborn child.
This controversy persists due to the reading brought by Article 2 of the Civil Code of 2002, where it states that a person’s personality begins through birth with life, however the law upholds the rights of the unborn child (BRASIL, 2002). On these points, it is emphasized that these are rights in the civil sphere, while the law saves any right of the unborn child.
However, the definition of unborn child does not fit in what is still only an embryo, because the being conceived and not born corresponds to the embryo after nidation, that is, after fixation in the inner wall of the uterus. Thus, there is no talk of embryo rights, however, Tartuce (2015) points out the importance of legislation harboring the prediction about such technologies.
In this tuning path Cervi questions,
(…) diante das inovações biotecnológicas de edição genética embrionária, seria possível promover uma interpretação acerca de intimidade e identidade e dos direitos da personalidade em um momento até mesmo anterior ao nascimento com vida, ou antes, à própria consideração de ser o embrião nascituro? (CERVI, 2019, p. 13).
In the midst of such a gap, the author defends a reframing of legal provisions according to the inevitable modern demands in order to protect the enshrined principle of human dignity (CERVI, 2019).
It is inferred that ethical and cultural values are related to each people and nation, while the human essence and human composition is unite, in this sense, Rodotá (2010) induces about the possibility of editing human embryos that receive a physical body designed according to the determination of someone demeans against human rights.
2.5.1 ISSUES RELATED TO EUGENIA
The glimpse and enchantment before the perspectives of cure from genetic editing become a concern, even in view of the possible interferences aimed at shady interests, based on cultural aspects, considering that the control of the technique is used in the choice of physical characteristics, such as height, eye color, hair, face shape, etc. (CERVI, 2019).
Thus, the concerns turn to the risks of eugenic practices, considering the interest of the human being here that is beautiful and distant from the abnormal or ugly, for Cervi (2019) the desire for beauty and youth has always accompanied man, being proof of this, his need to express perfection in works of arts, as well as is verified in literary narratives when describing characteristics of young and attractive characters.
In a simple way, eugenics consists in the selection of individuals from their genetic characteristics in order to improve the descendants that will be born. Regarding genetic editing Ormon et al. (2017) warns of the possibility of it being used for the selection of characteristics that go beyond therapeutic interests.
For Bobbio (2016) the concept developed in England in the nineteenth century, is teamed the theories of the heredity of racial biologicals and the subversive interpretation of natural selection proposed by Charles Darwin, according to which the most adapted survives, that is, the one with better genetic characteristics will survive.According to the indoctrinator, such theories originated practices erroneously applied in racist political contexts: where racial purification was preached.
Depending on this observation, Ormon et al., (2017) in any respect, eugenics is a dangerous practice, reinforcing prejudice stemming from the definition of what would be normal, or acceptable in society, as has historically occurred, the improvement of human DNA, without the therapeutic objective associated with a genetic determination, which supported by the state generated disastrous consequences.
Therefore, genetic improvement should never be used to reinforce the prejudice of stereotypes, especially knowing what the belief in the supremacy of a race can cause, as occurred in Nazi Germany, where it was believed that the Aryan race for being superior to others should dominate, in this regard Cervi (2019, p.05) states “the claim to ethnic cleansing and promotion of pure race and Aryan beauty, generated to his setback, much sadness, exclusion, misery and death, as well as feelings of shame.”
Thus, the possibility of eugenic practices generates concerns about a possible selection of individuals and their characteristics as a determining pattern, which would generate a loss of human diversity.
2.5.2 SOCIAL IMPLICATIONS
Within the ethical impasses of human genetic editing, it is worth discussing briefly around the social implications in the possible scenario of individuals whose characteristics were previously chosen and artificially determined.
Notifiedly, the technique is restricted to protocols that prevent its application, but in a possible reality in which its implementation is regulated, Ormon et al. (2017) warn that the social consequences are one of the most important points, given the success because it is likely to make even greater the social inequalities already faced today.
It is emphasized that even the slightly more complex health procedures are often restricted to those who can have good amounts, such as assisted reproduction, according to Cervi (2019) biotechnological procedures of application in the health area are possible to a small group of people, and there are no prospects around a wide access to the best curative therapies.
It is therefore the question of Singer (2017, p.135) “what will happen to those who do not have money to go to the genetic supermarket? Will your children be predestined to mediocrity?”
Surely each person seeks the best for himself and his own, it is known that the human being does not measure efforts to seek what gives him quality of life and safety. What once seemed utopian today is not so far away, but as for the already marginalized the future remains fraught with uncertainty.
According to Singer (2017) in this logic, the gene market could favor those with greater purchasing power to insert in the genetic lineage of their descendants genes encoding characteristics that can favor intelligence, aptitude for the practice of certain sports, among others (SINGER, 2017). The author also cites the exclusion of the “genetic lottery” to refer to the possible impacts caused by the artificial choice of desirable qualities.
3. FINAL CONSIDERATIONS
The present study aimed to bring an interdisciplinary approach scoring the main scientific, ethical-philosophical and legal repercussions brought by genetic editing in humans from the Crispr-Cas9 technique, such a biotechnological mechanism of genetic engineering opened new precedents in relation to the treatment and combat of human pathologies hitherto regarded as insurmountable. Thus, it sees it as an inevitable technology in postmodernity.
However, a universe of possibilities stems from the application of genetic manipulation through the CRISPR-Cas9 system, which alerted the scientific community, since it proves effective, accessible and fast, but the experiments still bring other inconclusive results in the face of possible errors in the performance of the tool, which can culminate in unpredictable and deleterious effects for the organism.
It is also concerned with the use of shady purposes such as human genetic improvement, a practice vehemently disproved for arouseing eugenicist ideals, which in the past led to real disasters under the justification of belief in higher races.
Considering the clear difficulty of the human being in obeying the limits necessary for the balanced use of environmental resources, aiming at the ecologically balanced environment. There have been concerns about the social inequality that a technique of such magnitude can cause, since such procedures will certainly be exhaustively expensive, leading to more segregation among humans whose parents were able to pay for desirable genetic characteristics and predispositions versus humans conceived under the genetic lottery.
Among the issues related to legal protection that orbit around the theme, it is found that the genetic composition of each individual is a patrimony of the entire human family, as provided for by organizations of international protection, which considers it an inviolable asset, essential for maintaining the principle of dignity of the human person, and can never be used for segregationist purposes.
The protection of genetic heritage is also projected at the national level, in order to prohibit any manipulations involving human genetic material, such as procedures involving cloning and human embryos. It is interpreted that the prohibition falls on the editing techniques related to the CRISPR-Cas9 system. It is worth mentioning the recent regulation of gene therapy at the experimental level, whose regulatory responsibility lies with the National Health Surveillance Agency – Anvisa.
Faced with the future with inevitable improvement and improvement of biotechnological mechanisms, there remains a legal-normative need regarding such practices, focusing on the considerations of bioethics, as a matter that seeks to establish the correct means for the application of procedures involving the Environment and human health, increasingly consolidating the Bioright and the principles that govern it.
AGÊNCIA NACIONAL DE VIGILÂNCIA SANITÁRIA – ANVISA. Resolução da Diretoria Colegiada – RDC Nº 260, de 21 de Dezembro de 2018. Dispõe sobre as regras para a realização de ensaios clínicos com produto de terapia avançada investigacional no Brasil, e dá outras providências. Disponível em:< https://www.in.gov.br/materia/-/asset_publisher/Kujrw0TZC2Mb/content/id/57218930/do1-2018-12-28-resolucao-da-diretoria-colegiada-rdc-n-260-de-21-de-dezembro-de-2018-57218634> Acesso em 17 jun 2021.
AMABIS, J. M.; MARTHO, G. R. Biologia das células. v. 1. São Paulo: Moderna, 2010.
BOBBIO, N. Dicionário de Política. Brasília: Universidade de Brasília, 2016.
BRASIL. Constituição da República Federativa do Brasil de 1988. Disponível em: < http://www.planalto.gov.br/ccivil_03/Constituicao/Constituicao.htm>. Acesso em 28 jan 2021.
BRASIL. Lei Nº 11.105, de 24 de Março de 2005. Disponível em:< http://www.planalto.gov.br/ccivil_03/_Ato2004-2006/2005/Lei/L11105.htm>. Acesso em 28 jan 2021.
BRASIL. Lei nº 13.123, de 20 de maio de 2015. Regulamenta o inciso II do § 1º e o § 4º do art. 225 da Constituição Federal, o Artigo 1, a alínea j do Artigo 8, a alínea c do Artigo 10, o Artigo 15 e os §§ 3º e 4º do Artigo 16 da Convenção sobre Diversidade Biológica, promulgada pelo Decreto nº 2.519, de 16 de março de 1998; dispõe sobre o acesso ao patrimônio genético, sobre a proteção e o acesso ao conhecimento tradicional associado e sobre a repartição de benefícios para conservação e uso sustentável da biodiversidade; revoga a Medida Provisória nº 2.186-16, de 23 de agosto de 2001; e dá outras providências. Brasília, 20 de maio de 2015. Disponível em:< http://www.planalto.gov.br/ccivil_03/_ato2015-2018/2015/lei/l13123.htm> Acesso em 16 jun 2021.
BRITO, N. B. V., Nascimento, S. M. C. Herança da vida: reflexões ético-jurídicas acerca do Patrimônio Genético. Brasil, Editora Dialética, 2021.
BOEL, Annekatrien et al. BATCH-GE: Batch analysis of Next-Generation Sequencing data for genome editing assessment. Scientific reports, v. 6, n. 1, p. 1-10, 2016. Disponível em:< https://www.nature.com/articles/srep30330>. Acesso em 01 jun 2021.
CERVI, T. M. D. Dorian Gray Na Moldura Do Século Xxi: Reflexões Jurídicas Em Edição Genética Embrionária. RJLB, Ano 5 (2019), nº 3. Disponível em:< http://www.cidp.pt/revistas/rjlb/2019/3/2019_03_1703_1721.pdf> Acesso em 19 jun 2021.
CLEMENTE, G. T. Avanços e desafios na edição gênica em seres humanos. In NICOLETI, C. E. et al. Biodireito, Bioética e Filosofia em Debate. Almedina, São Paulo. 2020.
Conferência Geral da Organização das Nações Unidas para a Educação, Ciência e Cultura (UNESCO) 29.ª sessão. Declaração Universal do Genoma Humano e dos Direitos Humanos. 11 de novembro de 1997.
GORCZEVSKI, C. Direitos humanos, educação e cidadania: conhecer, educar, praticar. Santa Cruz do Sul: Edunisc, p. 16, 2009.
HABERMAS, J. O futuro da natureza humana. Tradução de Karina Jannini. 2ª ed. São Paulo: WMF Martins Fontes, 2016.
HAYDEN, C. E. Should you edit your children’s genes?. Nature News, v. 530, n. 7591, p. 402, 2016.
HODSON, D. Realçando p papel da ética e da política educação científica. In: Dália Melissa Conrado, Nei Nunes-Neto. Questões sociocientíficas: fundamentos, propostas de ensino e perspectivas para ações sociopolíticas. Brasil, Editora da Universidade Federal da Bahia, 2018.
JUNQUEIRA, D. China confirma o nascimento de terceiro bebê geneticamente modificado. Olhar Digital. Disponível em:< https://olhardigital.com.br/2019/12/31/ciencia-e-espaco/china-confirma-nascimento-de-terceiro-bebe-geneticamente-modificado/> Acesso em 19 jun 2021.
LAMPHIER, E. et al. Don’t edit the human germ line. Nature, v. 519, p. 410-411, mar. 2015. Disponível em:< https://www.nature.com/news/don-t-edit-the-human-germ-line-1.17111> Acesso em: 03 de mai 2021.
MALUF, A. C. R. F.D. Curso de bioética e biodireito. 3ª ed. Atlas. São Paulo. 2015.
NAVES, B. T. O.; GOIATÁ, S. R. Direitos Humanos, patrimônio genético e dados genéticos humanos: crítica à doutrina dos dados genéticos como interesse difuso. Revista de bioética y derecho, n. 40, p. 63-81, 2017.
NETO, F. V. L. Direitos humanos de 4ª Geração. DHNET, 1998. Disponível em < http://www.dhnet.org.br/direitos/textos/geracaodh/4_geracao.html> Acesso em 22 de mai de 2021.
NOVARTIS. Aprovado o registro da primeira terapia gênica para AME no Brasil. 18 Agosto 2020. Disponível em:< https://www.novartis.com.br/news/aprovado-o-registro-da-primeira-terapia-genica-para-ame-no-brasil> acesso em 17 jun 2021.
ORMOND, K. E. et al. Human germline genome editing. The American Journal of Human Genetics, v. 101, n. 2, p. 167-176, 2017.
REIS, É. V. B.; OLIVEIRA, B. T. Crispr-Cas9, Biossegurança E Bioética Uma Análise Jusfilosófica-Ambiental da Engenharia Genética. Veredas do Direito: Direito Ambiental e Desenvolvimento Sustentável, v. 16, n. 34, p. 123-152, 2019.
RODOTÁ, Stefano. La vida y las reglas: entre el derecho y el no derecho. Traduzido por Andrea Greppi. Madrid: Edi-torial Trotta, 2010.
SCARMANHÃ, B. O. S. G. SILVA, M. F. GARÉ, C. C. T. Os avanços biotecnológicos e da engenharia genética: sob a perspectiva da reprodução humana assistida e seus reflexos no direito de família. RJLB, Ano 5 (2019). Disponível em:< http://www.cidp.pt/revistas/rjlb/2019/3/2019_03_0259_0279.pdf> Acesso em 11 jun 2021.
SANDEL, M. Contra a perfeição: ética na era da engenharia genética. Rio de Janeiro: Civilização Brasileira, 2013.
SANDER, J. D.; JOUNG, J. Keith. CRISPR-Cas systems for editing, regulating and targeting genomes. Nature biotechnology, v. 32, n. 4, p. 347, 2014.
SINGER, P. Ética no mundo real: 82 breves ensaios sobre coisas realmente importantes. Traduzido por Desidério Murcho. Lisboa: Edições 70, 2017.
TARTUCE, F. Manual de Direito Civil. Vol. Único. 5ª Edição. Editora Método. São Paulo. 2015.
THOMPSON, Deborah J. et al. Genetic predisposition to mosaic Y chromosome loss in blood. Nature, v. 575, n. 7784, p. 652-657, 2019. Disponível em:< https://www.nature.com/articles/s41586-019-1765-3> Acesso em: 18 jun 2021.
VENOSA, S. S. Direito Civil-Parte Geral. 7 ed. São Paulo (SP): Atlas, 2007.
 Academic of the Bachelor of Law course. ORCID: https://orcid.org/0000-0002-0096-7153
 Bachelor of Law. ORCID: https://orcid.org/0000-0001-7902-079X
 Guidance counselor.
Submitted: September, 2021.
Approved: September, 2021.