Is gene editing dangerous?

How safe is the widespread use of techniques such as CRISPR-Cas9?

Gene editing is defined as any genome engineering process by which DNA is inserted, removed or replaced by nuclease enzymes.DNA is inserted, deleted or replaced by nuclease enzymes..

Beyond the "textbook" definition, such practices lead to a number of ethical considerations that certainly need to be taken into account. In 2015, the first attempt to genetically modify a human embryo was given the green light, followed by experimentation aimed at improving the resistance of these unborn infants to HIV.

Following this, in April 2016, Nature News reported that Professor Fredrik Lanner's research team at the Karolinska Institute in Stockholm had received the necessary ethical approval to begin research involving human embryo editing, a practice strictly forbidden until just a few years ago.

The barrier has been crossed: the experimental field is no longer confined to laboratory animals or the treatment of chronic patients.The experimental field is no longer limited to laboratory animals or the treatment of chronic patients, but human beings are potentially capable of modifying the attributes of people even before they are born. Of course, with these findings, the question of whether gene editing is dangerous is extremely common in the general population.

Is gene editing dangerous? A possible double-edged sword

Before diving into the ethics of these practices, it is necessary to understand how they work, even if only briefly. At present, genome editing is based on four different techniques:

• Meganucleases: use of natural nucleases that break the phosphodiester bonds of the DNA chain.
• Zinc fingers: structural motifs present in proteins that, if modified, can show high specificity for certain DNA regions.
• TALEN: use of restriction enzymes that can be designed to identify and "cut" into specific DNA sequences.
• CRISPR-Cas9: this technique requires a section of its own.

What is CRISPR-Cas9?

This technique requires a mention of its own, as it has popularized gene targeting in the world of science. While the modification and use of zinc fingers costs an average of 30,000 euros per experiment, with CRISPR-Cas9 it only takes a couple of weeks of work and a budget of 30 euros.. If only for economic reasons, this methodology has opened an infinite number of doors in the world of genetic engineering.

To understand this technique we have to understand the two components of its name. Let's move on:

• CRISPR: a genetic region of some bacteria that acts as an immune mechanism against some viruses.
• Cas9: an enzyme that acts as a "genetic scalpel", i.e. it cuts and adds new regions of DNA with great precision.

In general terms, we could say that the CRISPR-Cas9 system is in charge of destroying the regions of genetic material of the virus that has infected the bacterium, inactivating its pathogenic capacity.inactivating its pathogenic capacity. Beyond that, this sequence allows the integration and modification of regions of viral DNA in the bacterium itself. Thus, if the virus re-infects the microorganism, it will "know" its nature much better and will act more efficiently against it.

To keep things simple, we will say that this methodology allows DNA modification at the cellular level, since the cuts and modification are not only applied to viral components. The RNA encoded in the CRISPR DNA region acts as a "seeing-eye dog", guiding the Cas9 enzyme to the exact location in the cell's DNA where cuts and pastes of genetic sequences are to be made. Although it requires a major exercise in abstraction, this technique is still a fascinating microscopic mechanism.

The lower costs and ease of use of this technique have marked a new stage for genomic engineering, which, without exaggeration, has led to the development of a new approach to genomics.Without exaggeration, this represents a new window for the concept of human life and evolution as we know it. But is genetic engineering dangerous?

In the world of ethics, not every end justifies the means

The dogma that "science is unstoppable" is an imperative by which is an imperative by which research has been guided over the last century, and it has an interesting double reading: first, scientists are not willing to stop. Naturally, the more one knows the more one wants to know, since each discovery results in the raising of a series of questions that must be answered.

Second, this statement assumes that "whatever can be done, must be done". This is a technological imperative, since it is the obligation of any professional to expand the bases of human knowledge, provided that the new information promotes the welfare and wisdom of the population. Beyond an opinion, an interpretation of the principle of responsibility proposed by the German philosopher Hans Jonas must be taken into account:

"Act in such a way that the effects of your action are compatible with the permanence of an authentically human life on Earth."

So, is anything goes as long as the human species and its permanence on the planet are not compromised on a general level?

Finally, it should be noted that all these techniques are ethically neutral.morality applies to the use to which they are put, and they should not be judged on the basis of their initial premise.

Gene editing in the germ line

Of course, germline gene editing is the most controversial area of research in recent times. We are talking about the modification of life during its earliest stages: fetal development..

For example, in 2015 a group of researchers at Sun Yat-sen University (Guangzhou, China) genetically edited embryos in order to eliminate the gene that causes beta-thalassemia, a very serious disease that affects the blood.

Although the research did not get very far because of the poor results, the aim was still clear: to break through the barrier of "natural" Biological mechanisms to prevent the occurrence of diseases in newborns.

The two risks most raised with regard to these techniques are eugenics (the possibility of selecting human beings with certain characteristics) and the uncertainty that this practice brings (due to the lack of knowledge of how it may affect future generations or the potential danger of putting these tools in the wrong hands).

In addition, the scientists who oppose this type of practice base their arguments on four essential pillars:

• The technology is not yet in a position to be safely applied, as its effect on the individual and future generations is not known.
• Alternatives already exist to prevent the birth of children with severe congenital defects.
• There is the likelihood of applying these techniques for non-therapeutic purposes.
• Conducting reckless experiments may cause the general population to lose confidence in science.

Of course, disagreeing with these points is difficult. The scientific community does not completely dismiss these practices, but rather speaks of caution and of building bridges when necessary. and to build bridges when necessary. In the words of scientific papers on the subject:

"If a case were to emerge that clearly showed the therapeutic benefit of germline modification, we would be committed to an open dialogue about the best way to proceed."

For this reason, some scientists propose the prohibition of this type of scientific approach in all countries that do not have strict regulations while the social, ethical and environmental implications of these practices are not fully elucidated. In the meantime, education and popularization of the population about this new era of knowledge would also be promoted, so that people not related to the subject can understand and reflect on the benefits and repercussions they bring.

Conclusions and personal opinion

Strange as it may seem in a purely informative space, in the opinion of this writer, to present this type of ethical considerations and not give a personal opinion is like throwing a stone and hiding one's hand.

First of all, it is necessary to recognize that "natural alteration of things" is something that human beings have been doing for centuries.. Not everything is based on the basal genetics of the individual, for example, natural selection is a mechanism that no longer applies to our species. We survive despite our pathologies, some of them chronic, which in nature would have automatically erased us. This translates into a biased gene conversion, as it does not respond to adaptive evolution.

Moreover, we have been modifying the species in our environment for centuries through genetic selection (not transgenesis) to obtain maximum benefit from the land and the environment around us. It is no coincidence that various scientific communities are proposing that this geological era be renamed the Anthropocene. Not only have we modified ourselves as a species by varying natural genetic selection, but also the environment has been completely transformed based on our benefits.

This is why the "naturalness" of human beings is an empty and meaningless concept.. Even so, this should not mean that "from now on everything goes". Science is knowledge, and knowledge is responsibility. Any scientific practice must seek the general welfare in one way or another, but also, as scientists, we have the obligation to transmit our intentions and results to the population in a reliable and friendly way. This, in many cases, implies adapting to the pace of social change and the demands of the general population.

From this point on, the limit is set by each individual: is it necessary to disregard general opinion if what is sought is the common good? to what extent should the scientific community wait for certain methodologies to be implemented? can knowledge be obtained without risk? So, is gene editing dangerous? The debate is open.

Bibliographic references:

• Capella, V. B. (2016). The gene editing revolution through CRISPR-CAS 9 and the ethical and regulatory challenges it entails. Cuadernos de bioética, 27(2), 223-239.
• de Miguel Beriain, I., & Armaza, E. A. (2018). An ethical analysis of new gene editing technologies: CRISPR-Cas9 under debate. In Anales de la Cátedra Francisco Suárez (Vol. 52, pp. 179-200).
• Lacadena, J. R. (2017). Genomic editing: science and ethics. Revista Iberoamericana de Bioética, (3), 1-16.