Ethics of Gene Editing

Image Source: The Scientist

Science of Gene editing is raising ethical and safety questions. These new technologies are increasingly pushing us to think of humans in mechanistic terms. This is why there are fears of leading us to accept mere narrow ways of being humans where the rich and powerful elite minority will have control over the rest of the world and humanity. Besides, these possible social harms there are very real dangers of physical harm as well as losses for our species. The specific technology that has raised these dangers is CRISPR-Cas-9. This technology has made a quantum leap to what has been genetic engineering since 1970. Genetic engineering only allowed researchers to transfer copies of whole genes to targeted genomes while the new gene-editing technologies enable scientists to make such changes more easily, reliably and cheaply. These technologies can be programmed to target one or more specific stretches of DNA. The targeted DNA can be shut off (deleted) or new DNA can be pasted in. Although these new technologies are far more accurate than the previously available tools, they are still prone to cause unintended off-targets or fail to make all the hoped-for changes resulting in a mixture of the edited and unedited cells within an organism (mosaicism). This being so, this study wishes to raise the question, will it bring about human flourishing? We try to translate Aristotle’s eudaimonia as human flourishing. Others translate it as human well being or happiness. Working at the level of human DNA can promote human health and well being and may promote human flourishing. But gene editing gives the power of editing the genomes of animals and plants too. It has almost given us control over evolution. Therefore, the ethics of gene editing puts huge responsibility at the feet of humanity. We need to rise above our narrow anthropocentric ethics and embrace ethics of care that is open to humans becoming co-creators with the divine.

As long as the genetic code of a particular feature is known, scientists can employ CRISPR-Cas9 to insert, edit or delete the associated gene in the genome of any living organism. This technique is far simpler and effective than any other gene manipulation technology known to us so far. This means science has brought us on the threshold of second genesis. Scientists have used CRISPR-Cas9 to create Schwarzenegger-like super muscular physiques for dogs by introducing single-letter DNA changes to the gene that controls muscle formation. In another case, scientists have activated a gene in a pig genome that responds to growth hormone and we have micro pigs no bigger than cats that can be then sold as pets. Further scientists have used the same technology on Shaabi goats in order to let them grow muscle and long hair. In the plant world CRISPR-Cas9 is increasingly used to edit crop genomes that promise to bring changes in our diets and respond to our food security issues. Besides, this technology has produced resistant rice, increased the shelf life of tomatoes. These achievements are exciting but gene-editing of human DNA shows great promise as well as peril. It offers possibilities to edit mutated genes in humans to heal cystic fibrosis, sickle cell disease, Duchene muscular dystrophy, some forms of blindness, severe combined immunodeficiency among many other disorders. It is also used to Humanize DNA of animals like pigs so that they can be harnessed to harvest organs from humans. CRISPR-Cas9 promises a huge medical revolution and may even enable us to treat HIV-AIDs or hunt down cancerous cells and treat some cancers.

But there are tremendous ethical issues with the prospects of the use of this technology particularly on humans. It can be used as therapy, enhancement as well as may be used to cause harm. Besides, the genetic changes that it introduces in some cases especially in germ-line therapeutics will be transmitted to the next generation which might lead to alteration of human genetic composition. Its use therefore, may pave the way for emergence of transhumanism/ post-humans. This means we have serious issues on our hands to address ethically. What slow paced random mutations and natural selection gave us we can change today in a quick time. We are indeed living a great revolution in the making. For the first time humanity seems to have gained mastery over evolution. We seem to have the power to decide the destinies of all life on earth. We are marching into a new eugenics. Therefore, we need to bring into our conversation this new technology and the impacts that it will make on us and life on this planet earth. Our response cannot be phobic. It has to be critical and has to assess the pros and cons of this technology and trace an appropriate ethical response. Entire humanity has a stake in the way this technology will unfold. Therefore, we do not really have an option to stay out of this conversation. It is an ethical imperative of our time. If we fail to address it, we may lead to the extinction of humanity as well as life on earth. There are great possibilities for human flourishing as well as flourishing of other life forms in this technology. We may even revive long extinct species. But with great power comes great responsibility. We have the challenge to influence the use of this technology so that human dignity and inviolability as well as preciousness of all forms of life are maintained. The issue is complex and it is not easy to draw a line for the use of this technology. This study is a small contribution in this direction. It has to be improved with dialogue, debate and further research. We begin our study with a quick view on technology that has put evolution under human control. We then follow it up with Aristotle’s understanding of human flourishing. Then, we take up ethics of care to divest Aristotle’s notion of human flourishing of anthropocentric moorings and end with a proposal that ethics of care can respond to the ethical quandaries raised by gene-editing technology known as CRISPR-Cas9.

Understanding CRISPR-Cas9

The term genome stands for the entire genetic instructions found in an organism. It tells organisms how to grow, how to sustain themselves and how to transmit the genes to their offspring. The building blocks of a genome is made of deoxyribonucleic acid (DNA) which itself is made of four nucleotides (AGCT). Nucleotides are chemical groups also called bases of Adenine (A), Guanine (G), Cytosine (C) and Thymine (T). These molecules are connected in long single strands. Two of these strands go on to form the double-helix structure of DNA. It is a bit like a twisted ladder in a long spiralling coil. To transform the instruction contained in the DNA into proteins, the cell makes use of an intermediary molecule called ribonucleic acid (RNA). RNA has three of the same bases except Thymine (T) is replaced by Uracil (U). Besides, RNA has an additional oxygen atom than DNA. RNA acts as a messenger from the nucleus (DNA) to the outer regions of the cell where proteins are produced. From DNA to RNA to Proteins is the central dogma of molecular biology. Scientists were trying to take control over this central dogma through what we called genetic engineering or recombinant biotechnology. CRISPR-Cas9 is technology that seems to have given this mastery to humanity.

CRISPR-Cas9 mimics the technique used by bacteria to fight viral attack. The acronym CRISPR stands for clustered regularly interspaced short palindromic repeats. It simply means that the structure of the DNA is unique where interspacing strands regularly interrupts the repeating strands. It is not surprising to find that the cells have repeating DNA strands. After all DNA is put together by a play of four bases. But here is something unique and special. The repeating strands are truly identical and always separated from its neighbour by a similarly sized random spacer sequence. Every cell of bacteria has a different CRISPR array due to unique sequence interspaced repeats. Since CRISPR was so common, scientists thought that nature was doing something special with it. It was found that the snippets of DNA sandwiched between the repeating sequences were a perfect match of the DNA of the known bacterial viruses. It was also found that the more presence of those matches in a bacteria meant the lower chances of viral infection. This hinted that CRISPR was part of the bacterial immune system that enabled them to fight viral attacks. This motivated researchers to figure out how CRISPR worked. It turned out to be a bacterial strategy acquired over a long time of evolution to fight viral attack. It is an antiviral defence mechanism. This is why scientists tried to hunt down genes that blocked viral infection. It was discovered that CRISPR functioned like a molecular vaccination card: by storing the memory of the past viral infections in the form of spacer DNA sequences buried in repeat spacer arrays which the bacteria use to recognize and destroy the same invading phages in the future. Soon it was shown that molecules of RNA were involved in CRISPR antiviral defence. It coordinated the recognition and destruction by singling out both DNA and RNA molecules of the invading virus during infection that matched with any molecules in the DNA of the bacteria to initiate an immune response. Scientists learn about the genes by looking at the chemical composition of the genes . This helps them to know amino acid sequences that a gene produces. Using these methods scientists had already figured out kinds of cas genes that invariably coexisted with CRISPR regions. All CRISPR regions across different organisms were found to be associated with cas genes. It was found that cas1 were functioning as genetic scissors. This function allowed the scientists to theorize how CRISPR would steal genes from the attacking virus. Cas 6 was found to be involved in cutting long CRISPR-RNA molecules into smaller chunks. Scientists found several other cas proteins that produced DNA or RNA cutting enzymes and soon found Cas9 , a protein that cuts the DNA of a virus. Thus, the immune mechanism of the bacteria worked with the CRISPR -RNA identifying and pairing with viral DNA to be chopped into pieces and thus disabling it by Cas9 in the presence of tracrRNA.

Today CRISPR-Cas 9 is a powerful gene editing tool. This means scientists can engineer Cas9 and the RNA molecules to target and cut any DNA sequence of our choice thus opening the full power of CRISPR. Today it has become a tool of gene editing and shows great promise as Cas9 can cut DNA that we desire. RNA acts like a GPS guiding the coordinates of attack and Cas9 works like a weapon to eliminate the target. This means scientists can now rewrite the code of life. Scientists are using this tool to engineer the DNA of countless organisms as well as genetic material in human cells. CRISPR has fast become the holy grail of gene manipulation that can easily, accurately and quickly fix defects in the genetic code. This means CRISPR has become a therapeutic tool. This opened the road for gene editing inside a living cell. There is a challenge. Human DNA after being cut immediately sets in a repair process that joins the cut DNA strand with new bases or deletes existing ones of the DNA. This means unwanted permanent changes are introduced in the DNA when the repair process is completed. This means the gene will most likely be altered after being targeted by CRISPR, sliced apart and repaired by the cell. But as time went on, Scientists were able to take control of the error prone repair process of the cell and engineer the change that they wanted to introduce in DNA. Along with this mastery over the code of life comes great responsibility for which it appears we as individuals as well as species are not yet ready. CRISPR- revolution has come to stay; we have the great responsibility to develop ethical vision that will prevent it from being abused.

Understanding Human Flourishing

Human flourishing cannot be simply reduced to happiness. Aristotle’s eudaimonia is often greeted as a theory of human well being. Aristotle’s notion of human flourishing is an effect of fulfilment of our nature and is therefore teleological in character. It is also subjective in character and hence involves realizing one’s diamond or nature. It involves fulfilment of our potencies. Before Aristotle, Socrates taught that eudaimonia is the knowledge of the ultimate good of humanity. Plato thought that eudaimonia is the highest and ultimate moral thought and action. We can see that right from the Socrates eudaimonia has shades of pursuit of excellence. Aristotle did not see eudaimonia as just limited to pursuit of virtue as Plato and Socrates want us to think but one that embraced virtuous life with practical wisdom/phronesis. It is important to open our thinking to eudaimonia as also pursuit of phronesis. Otherwise while seeking our ethical response we may come to a roadblock when we may assume what we deem a human nature has to honour or respect. Often we confuse nature and culture as we define human nature. Nature-fulfilment perspectives of eudaimonia draw the boundaries for all biotechnologies, particularly gene editing and do not allow them to be employed beyond what is fixed as human nature. These boundaries have their importance because there are real fears that these technologies may diminish human flourishing. This is why we may need Phronesis to deal with ethical issues rising out of gene editing to ensure human flourishing.

Praxeology is a science of human conduct and action. It refers to purposeful action that the Greeks called praxis. We need phronesis to guide humans in the practice of gene editing. Phronesis has a profound relationship with eudaimonia. Phronesis is to be at the service of human flourishing. Aristotle thus, presents phronesis as the highest intellectual virtue. Human flourishing requires practical wisdom which becomes the capacity to act ethically. Aristotle’s Book Nicomachean ethics offers the following argument to convey us the importance of phronesis:

  • There is an ultimate end that is the chief good
  • The chief good or the ultimate end is eudaimonia
  1. Eudaimonia is complete and self sufficient
  2. Moral virtues aim towards eudaimonia. Virtues actions are done for the sake of eudaimonia.
  3. Moral virtues are realized in actions (praxis). Therefore, actions are aimed towards eudaimonia
  4. Phronesis involves choice and initiate action

We need a habitual disposition which Aristotle calls Hexis to act in accordance to practical wisdom. Habituation is not mindless. It requires assessing the situation and seeing what is called for. This means it requires the applicative dimension of phronesis. It requires us to apply the universal principle in a concrete situation. For Aristotle, virtue is not a feeling or a capacity. It is Hexis. To form hexis one therefore, walks on paths and the resulting praxis. In shaping the path one has to work on two aspects: pleasure and pain. Thus, Aristotle bases virtue on pathe and praxis. He thinks that to be virtuous is to find the meaning of pathos (pleasure/ pain) and praxis in a particular situation. To realize the meaning, we need phronesis. Phronesis stirs our desire to move towards the telos or goal (eudaimonia). When Aristotle teaches that moral virtue is a mean position between excess and deficiency, he is not saying one is by character to have moderate emotional responses. The right emotional response depends on the situation: ‘to be affected when one should, in relation to the people one should, for the reasons one should, in the way one should, is both immediate and best, which is what belongs to excellence’. These appropriate responses are based on judgement of the practical wisdom or the phronimos. Even emotional response can be virtues if reason judges it to be the true demand of the situation. It is therefore not possible to be virtuous without phronesis or have phronesis without being virtuous.

Aristotle’s virtues action involves eudaimonia, arête ( virtue) and phronesis. If each of us cultivate virtue we can respond to all challenges posed by ethically difficult issues like gene editing. It means humans who chose human flourishing will not simply reject gene editing out of fright but will seek to make the practice of gene editing into a practice of virtue led by phronesis. Phronesis is closely associated with the virtue of logistikon (calculative reason) which has a sense of bouleuesthai ( deliberation). Thus, phronesis is intimately linked with deliberation and is defined as ‘that which has to do with things human and things one can deliberate about’. Therefore, phronesis is deliberative and not intuitive. Phronesis, therefore has the following features:

  1. Phronesis is an intellectual virtue
  2. It is deliberative and not intuitive
  3. It is end driven. It pursues the whole good of a person ( Eudaimonia)
  4. It results in virtuous action
  5. It is applicative. It applies the universal principle in a concrete situation.

The virtue of good deliberation (euboulia) can enable us to overcome two important drawbacks of Aristotelian virtue ethics. Aristotelian virtue ethics is subjective and anthropocentric. It is about an individual’s pursuits of virtuous life. Deliberation can open us to bring virtue and phronesis in our societies and communities. This has been already attempted by Joergen Habermas through his theory of communicative action. We need communicative action that will bring virtue and phronesis in our deliberations on the ethical issues raised by technologies of gene editing. This can be done by instituting ethical committees that would assist us to bring virtue in practice of gene editing and thus regulate it from being abused. Habermas’ theory of communicative action is reason-centric and might have its limitation to think together the flourishing of humanity alongside the flourishing earth and all its life forms. This is why we may have to bring ethics of care . Habermasian discourse ethics that is simply based on the force of reason has its limits. This means we need deliberative communicative action not just led by the reason but one that is also led by the heart. This will truly transform our deliberative communicative actions into acts of phronesis.

Towards Ethics of Care

he theory of communicative action of Habermas has its importance. He however sees that all deliberations are immanently guided by a rational structure. His inter-subjective deliberative mode of seeking the truth and the good, particularly in the context of difficult ethical paradoxes may be useful. We do need some minimum agreements before we begin our deliberations on these issues. Habermasian requirement of competence seems to become even more radical when it comes to communicative action concerning ethics of gene editing. These procedural matters and norms governing deliberations are indeed prerequisites on our part to enter into deliberation on issues concerning gene editing. The power of reason to debate and deliberate will assist us to seek common flourishing of the earth, life and humanity. But we have transcended reason bound communicative action otherwise it may lock us into the prison that Max Weber calls rationalization of society. It can also enslave us to instrumental reason which exchanges means for end. This means what are means of good life will become ends of life. Reason thus, has its limitations and we have to agree that it can disable the common flourishing of life, earth and humanity and may blind us so that we may promote the vested interest of the power elite and deem it as the flourishing of earth, life and humanity. This is why reason has to be complemented by care that will enable us to seek eudaimonia of the earth, life and humanity by bringing virtue and phronesis in our deliberations of ethics of gene editing.

Deliberative action that seeks ethical guidance for concrete cases of gene editing needs reason as well as care to save us from being manipulated by instrumental reason. When instrumental reason takes over, our deliberations cannot become acts of virtue and phronesis. Ethics of care will include ethics of dissensus taught by Ewa Ziarek so that we can disagree because we care to bring about the flourishing of humanity, earth and all life. We can trace ethics of care being developed in some areas of business ethics and feminist ethics. Ethics of care can be true fulfilment of the nature of humanity in the Heideggerian sense. Heidegger characterises human nature as dynamic Sorge/ Care and not some static essence. We can truly reach a fuller point of self realization by living an ethics of care that is leading to the common flourishing earth, life and humanity. Ethics of care does understand that all those involved in communicative action are ontologically laden and opens debate to safeguard the value of dialogical flourishing of the earth, life and humanity. This means dialectical reason is used not to dominate the discussion but to bring about an inter-related common flourishing of humanity, earth and life by the use of gene editing. Therefore, as we deliberate on ‘what out to be’ of humanity or even that of animals as we employ techniques of gene editing, we have to factor in the highest good ( eudaimonia) of earth, life and humanity. This means there are trialogical dynamics that we need to consider when we deliberate concrete decisions about gene editing. These deliberations will have to consider the nature/ fulfilment perspectives associated with eudaimonia with critical care so that the highest good of all the three coordinates ( earth, life and humanity) that form the trilogue has to be pursued.

Although the critical deliberations and communicative actions that we propose here demand competence on the part of the participant, it does not mean other citizens are left out of this task of regulating the powerful gene editing tool. For the good of life, our planet earth and humanity, all of us have to enter into the discussion into what Habermas calls the Public sphere. Led by reason and ethics of care, every citizen can deliberate and lead to contestation of public policies that he/she may deem as harming our interdependent and interrelated life on this planet earth. We all have a shared responsibility to bring virtue and phronesis in the practice of gene editing. Thus, the ethical committees may involve in specialized communicative actions that will deliberate on the concrete issues of gene editing and provide norms that will assure common flourishing of humanity, planet earth and life. The general public can open counter publics that will use dialectical reason as well as ethics of care so that common good of humanity, earth and life on it is dialogically discerned and pursued

Conclusion

The issue of gene editing being an evolving one, we cannot fully apply ethics based on purely deductive principles. We need to employ inductive methodology that remains open to the changing condition of research and practice as regards the domain of gene editing. Our study therefore, uses minimum deductive principles. This is why we avoid logocentric and positivist fixing of eudaimonia, virtue, phronesis, praxis etc., but remain open to the discernment through inter-subjective search for practices that will promote the flourishing of the earth, life and humanity. Our chief focus is to make the pursuit of virtue and phronesis immanent in the practice of gene editing through virtuous practice of deliberative communication complemented with ethics of care and phronesis.

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Hypocrisy is the tribute that vice pays to virtue.

- Fr Victor Ferrao