Editing life: The science, ethics and future of CRISPR

Photo: Reuters

The field of genetic engineering has been fundamentally altered by the advent of Clustered Regularly Interspaced Short Palindromic Repeats, more commonly known as CRISPR. 

Originally discovered as a component of the bacterial immune system by Francisco Mojica, this ingenious mechanism has been harnessed into a precise and versatile tool for editing the DNA of living organisms. 

The CRISPR system functions as a pair of molecular scissors, capable of cutting DNA at specific target sequences guided by a customisable RNA molecule.

Compared to earlier gene-editing techniques, CRISPR offers a simpler, cheaper and more precise approach to rewriting the genetic code in virtually any organism. This ease of use and enhanced precision means CRISPR stands at the forefront of genetic engineering today, offering hope for curing diseases, bolstering food security, and tackling environmental challenges. 

Yet, its power demands responsibility. As the world embraces this technology, collaboration between scientists, ethicists, policymakers, and the public will be essential to ensure its benefits are realised equitably and safely

The science behind CRISPR

At its heart, CRISPR is a gene-editing system that enables scientists to make precise alterations to an organism's DNA. The most widely adopted variant, CRISPR-Cas9, relies on two key components: Cas9 enzyme, which is a molecular pair of scissors that cuts DNA at a specific location and Guide RNA (gRNA), which is a small RNA molecule that directs the Cas9 enzyme to the exact spot in the genome where the edit is required.

Once the DNA is severed, the cell's natural repair mechanisms kick in, allowing researchers to insert, delete, or modify genetic sequences with remarkable accuracy. 

This precision has positioned CRISPR as a game-changer in genetic engineering, outstripping older techniques such as zinc-finger nucleases and transcription activator-like effector nucleases (TALENs) in both efficiency and accessibility.

Latest developments in CRISPR technology

The field of CRISPR research is advancing at a breathtaking pace, with breakthroughs continually expanding its potential.

One of the most notable recent developments includes the optimisation of CRISPR-Cas9. While it is already a highly effective tool, researchers are working tirelessly to enhance CRISPR-Cas9's precision. One persistent concern is off-target effects — unintended edits to the genome that could have unforeseen consequences. 

In 2023, scientists at the University of Michigan developed an improved variant called miCas9, which reduces off-target activity while maintaining editing efficiency, according to a study published in Nature Biotechnology. This refinement is a critical step towards safer clinical applications.

A more recent innovation, base editing, allows scientists to change individual DNA bases (e.g., converting a C to a T) without making a double-stranded break in the DNA. Pioneered by David Liu's team at Harvard University, this technique minimises the risk of unintended mutations and has been celebrated as a safer alternative for specific edits. 

A 2023 review in Nature Reviews Genetics highlighted its potential for correcting single-point mutations responsible for diseases like sickle cell anaemia.

But perhaps the most groundbreaking development came in December 2023, when the UK's Medicines and Healthcare products Regulatory Agency (MHRA) followed the US FDA in approving Casgevy, the world's first CRISPR-based therapy. 

Developed by Vertex Pharmaceuticals and CRISPR Therapeutics, Casgevy treats sickle cell disease and beta-thalassaemia by editing patients' blood stem cells to produce functional haemoglobin. 

Clinical trials reported in The New England Journal of Medicine showed that 93% of sickle cell patients remained free of severe pain crises for at least a year post-treatment — a monumental leap forward in gene therapy.

Beyond altering DNA sequences, CRISPR is now being adapted for epigenetic editing, which modifies how genes are expressed without changing the underlying code. A 2023 study in Cell demonstrated that CRISPR-based tools could silence or activate genes linked to neurodegenerative disorders, offering hope for conditions like Alzheimer's, where gene regulation is key.

Applications beyond human health

While CRISPR's medical breakthroughs often steal the spotlight, its applications extend far beyond healthcare.

In agriculture, CRISPR is being used to develop crops that can withstand pests, diseases, and climate change. For example, a 2023 study published in Plant Biotechnology Journal detailed the creation of a powdery mildew-resistant wheat strain, addressing a fungal disease that devastates global harvests. 

Similarly, researchers at the John Innes Centre in Norwich, UK, have used CRISPR to enhance the nutritional content of tomatoes, boosting levels of vitamin D.

CRISPR is also revolutionising industrial biotechnology. Scientists are engineering microbes to produce sustainable biofuels and bioplastics. 

A 2023 report from the University of Manchester showcased a CRISPR-edited bacterium capable of converting agricultural waste into bioethanol, a promising step towards reducing carbon emissions.

In conservation, gene drives — a CRISPR-based technique to spread specific genetic traits through populations — are being explored to tackle ecological challenges. For instance, researchers are investigating gene drives to reduce the fertility of invasive grey squirrels in the UK, protecting native red squirrels, as noted in a 2023 Nature Communications paper. However, this approach remains experimental due to potential ecological risks.

Ethical considerations

The power of CRISPR to reshape life itself brings with it profound ethical dilemmas.

The prospect of editing the human germline — DNA in eggs, sperm, or embryos that can be inherited by future generations — has sparked intense debate. While it could eradicate hereditary diseases, it also raises the spectre of "designer babies", where traits like intelligence or appearance are enhanced. 

The 2018 birth of CRISPR-edited twins in China, led by scientist He Jiankui, ignited global outrage and underscored the need for stricter oversight. The UK's Human Fertilisation and Embryology Authority (HFEA) currently prohibits germline editing for reproduction, reflecting widespread caution.

Moreover, even with improvements, the risk of off-target edits persists. A 2023 study in Nature Genetics found that while rare, such errors could accumulate over time, potentially leading to health issues in treated individuals or their offspring.

The cost of CRISPR therapies poses another ethical challenge. Casgevy, a one-time gene therapy treatment, has an estimated price of £1.7 million per patient in the UK, which raises concerns about accessibility, particularly in lower-income regions. A 2023 editorial in The Lancet called for global efforts to ensure equitable distribution of these life-saving treatments.

In agriculture and conservation, CRISPR's ability to alter ecosystems must be carefully managed. The unintended spread of gene drives, for example, could disrupt biodiversity, while enhanced crops might exacerbate economic disparities among farmers if access is unequal.

Challenges facing CRISPR technology

Despite its promise, CRISPR faces several hurdles.

For instance, off-target effects, though reduced, remain a barrier to widespread clinical use. Ongoing research aims to refine CRISPR tools further.

Getting CRISPR components into target cells safely and efficiently is also a logistical challenge. Innovations like nanoparticle carriers, highlighted in a 2023 Science Advances paper, are being explored to address this.

Additionally, the rapid pace of CRISPR innovation demands agile regulatory frameworks. The UK's MHRA and the EU's European Medicines Agency are adapting guidelines to balance safety with progress.

Ethical controversies have also fuelled public scepticism. A 2023 YouGov poll found that only 41% of Britons support human gene editing, underscoring the need for transparent dialogue.

The future of CRISPR

Looking ahead, CRISPR's potential is vast.

Beyond sickle cell disease, trials are underway for conditions like cystic fibrosis and Huntington's disease, with results expected by 2025.

CRISPR could enable treatments tailored to an individual's genetic profile, revolutionising healthcare.

If safely implemented, gene drives could curb diseases like malaria by altering mosquito populations, though rigorous testing is needed.

Epigenetic editing might unlock treatments for complex diseases like cancer and diabetes, where gene expression plays a pivotal role.