CRISPR e Gene Editing, potenzialità e implicazioni etiche

The Focus

S01E04: CRISPR and the new frontiers of Genome Editing - Potential and ethical implications

00:00 / 5:25

Pill extracted from episode S01E04 of the "Disruptive Talks" podcast: see the complete program of the episode on this page.

What is CRISPR

CRISPR is the acronym for Clustered Regularly Interspaced Short Palindromic Repeats, a family of bacterial genetic elements discovered in 1987 but whose function was only recently understood. These are short DNA sequences that contain the "instructions" to recognize and cut specific sequences of viral DNA during infection, as a defense mechanism of the bacteria.

The discovery

CRISPR was first observed in 1987 by Yoshizumi Ishino and colleagues in E. coli. However, its function remained unknown until the 2000s, when several research groups realized the role of CRISPR-Cas in bacterial immunity.

In 2005, three independent teams published their findings on CRISPR as an adaptive immune system. Pioneering researchers included Alexander Bolotin, Eugene Koonin, John van der Oost and Francisco Mojica.

The turning point came in 2012, when Emmanuelle Charpentier and Jennifer Doudna understood how to exploit CRISPR-Cas9 to modify DNA in a targeted way, laying the foundations for an innovative genome editing technique.

How CRISPR works

Simply put, the CRISPR system works a bit like the “genetic scissors” we use to cut DNA. Let's imagine we have a pair of special scissors, equipped with a mini-computer that acts as a GPS and tells the scissors the exact point where to cut.

This mini-computer is made up of a short sequence of RNA, called the “guide sequence”. The enzyme that acts as scissors is the Cas9 protein. By modifying the guide RNA sequence, we can precisely direct the Cas9 scissors towards the gene we want to cut, a bit like setting a destination on the GPS.

Once Cas9 has cut the DNA at the programmed point, the cell activates its repair mechanisms, which mend the cut. However, we can exploit this process by simultaneously providing the correct piece of DNA, which will be incorporated in place of the defective sequence. It is as if, while the cell mends the tear, we replace a torn piece of fabric with a new one. In this way we are able to correct the mutations underlying various diseases.

Impact of CRISPR

CRISPR has revolutionized biomedical research because it allows the genome to be edited with unprecedented precision, versatility and simplicity. The applications are countless and are leading to concrete progress in various fields.

For example, CRISPR is used to create animal models, such as mice or monkeys, with genetic mutations identical to those that cause human diseases such as Huntington's disease or cystic fibrosis. These "model organisms" allow us to study the mechanisms of diseases in more depth and test new drugs or gene therapies.

In the field of somatic gene therapy¹, CRISPR has been successfully used to correct mutations underlying serious diseases such as beta-thalassemia, sickle cell anemia and Duchenne muscular dystrophy by modifying the DNA of patients' somatic cells.

CRISPR also makes germline editing possible² and embryos. For example, harmful genetic mutations could be corrected before a child is born, ensuring a life free from serious diseases. However, the long-term impacts of such interventions are unpredictable and raise delicate ethical questions.

Ethical implications

While correcting genetic defects in embryos could eradicate terrible diseases, modifying the germ line can transmit unexpected alterations to descendants, with implications that go far beyond the individual. Additionally, cosmetic or human enhancement applications raise concerns about eugenics.

In the future, if properly regulated, CRISPR could truly defeat debilitating genetic diseases before birth. But given the unpredictability of long-term effects, caution is in order.

This is why in 2015 an international group of scientists called for a moratorium on the use of CRISPR in human embryos intended for implantation, due to the risk of reckless approaches and unwanted effects. Despite this, in 2018 the Chinese researcher He Jiankui announced the birth of the first children with DNA modified via CRISPR, causing controversy and his sentence to 3 years in prison.

The debate has also been heated in Italy. In 2017, the National Committee for Bioethics expressed its opinion recommending a ban on any experimentation on embryos, while it considered basic research on germ cells not intended for pregnancy to be admissible.

Possible topics for debate

It will be important, at the right time, to open a public debate to decide where to draw insurmountable boundaries on the use of CRISPR technology.

For example, is it right to modify the human embryo? And if one day it were possible to create genetically modified humans, would we allow it?

The issues that could lead to debate following the possible commercial development of this science are numerous:

Eugenics derives, with "tailor-made children" selected by parents
Social inequalities, with high cost access and more advanced countries potentially excluding developing countries
Discrimination against non-genetically modified people
Gene doping in sport, with genetically enhanced athletes
Militarization and use to create biological weapons

These are ethically complex questions, which have no easy answers.

Conclusion

In conclusion, CRISPR is a technology with enormous potential but which raises delicate ethical questions.

If addressed with an open spirit, empathy and rationality, these questions can lead us to reconcile scientific progress and the protection of human dignity. The future of CRISPR is in our hands. It is up to us to shape it wisely for the common good.

Insights

¹ Somatic gene therapy: consists of modifying the genome of somatic cells, i.e. cells that do not contribute to the germ line. The changes made are not passed on to offspring. It is used to treat hereditary diseases by correcting defective DNA in the patient's tissues and organs.

2 Germline: refers to primary germ cells (eggs and sperm) and their precursors. They contribute to the formation of embryos and the transmission of hereditary characteristics to offspring. Germline modification, unlike the somatic one, can transmit the genetic alterations introduced to descendants. This raises ethical concerns as the consequences could extend to future generations.

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