Recently, the US Food and Drug Administration approved two landmark gene therapies, Casgevy and Lyfgenia, marking a landmark in how we treat patients. These therapies are cell-based treatments for sickle cell disease (SCD) in patients aged 12 and older. Notably, Casgevy stands out as the first therapy to employ CRISPR/Cas9, a groundbreaking genome editing technology.
CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is a ground-breaking scientific breakthrough that has revolutionised the field of genetics. Imagine a highly precise pair of molecular scissors that can accurately cut and alter DNA. This technology allows scientists to edit genes with unprecedented precision, offering potential solutions to a myriad of genetic disorders and diseases. In simpler terms, CRISPR can be thought of as a sophisticated editing tool that enables us to modify the genetic code of organisms, ranging from bacteria to humans.
Casgevy utilises CRISPR/Cas9 to precisely cut and edit DNA, enabling targeted modifications. These edits prompt blood stem cells to produce more foetal haemoglobin, which improves oxygen delivery. When reintroduced into the patient, these cells reduce the sickling of red blood cells in sickle cell disease.
CRISPR’s reach extends far beyond a single application; it’s at the heart of at least 51 active clinical trials across the US, tackling a spectrum of conditions from renal cell carcinoma to various rare genetic disorders. For instance, a small study used CRISPR-edited immune cells to target and attack cancer cells. Scientists have also employed CRISPR for detecting DNA from cancer-causing viruses and RNA from cancer cells.
Beyond medical applications, CRISPR has proven invaluable in various research areas, including controlling transcription, modifying epigenomes, conducting genome-wide screens, and imaging chromosomes. Its impact extends to the alleviation of genetic disorders in animals. Moreover, its applications have reached agriculture, speeding up crop and livestock breeding, engineering new antimicrobials, and controlling disease-carrying insects with gene drives.
Notably, CRISPR is lauded for its ease of use, especially compared to older gene-editing methods. Before CRISPR, advanced gene editing was limited to a few specialised labs, but now, even high school students can modify complex genomes. Its customisable nature allows editing of any DNA segment within the human genome’s 3 billion letters, and it’s more precise than previous methods. Additionally, gene editing with CRISPR is significantly faster and can be scaled up for large-scale experiments. It’s also more affordable than previous techniques, further democratising genetic research.
In the book, A Crack in Creation, Jennifer Doudna, a co-inventor of CRISPR, recounts a pivotal moment when she realised the immense power of this gene-editing technology. Doudna describes the thrill of being able to rewrite the code of life, likening it to a “God-like” ability. However, like every new innovation, CRISPR also has some unintended consequences.
A key study by Kosicki et al, published in Nature Biotechnology in 2018, highlighted the potential for CRISPR to cause unintended mutations. This study revealed that CRISPR-Cas9, a commonly used system for gene editing, can cause large deletions and complex rearrangements in targeted DNA regions, which might lead to unforeseen genetic anomalies.
Another concern revolves around the accessibility and misuse of CRISPR technology. There are primarily two issues with CRISPR. First, as J Craig Venter, a pioneer in genome sequencing, points out, the ease and low cost of CRISPR pose risks of unethical usage, such as in the creation of designer babies. The 2018 case of Chinese scientist He Jiankui, who used CRISPR to genetically modify human embryos, underscores this danger. By allowing for the alteration of DNA sequences, CRISPR holds the potential to not only cure genetic diseases but also to enhance human traits such as intelligence, physical ability, or appearance. This power raises the spectre of eugenics, a concept historically marred by its association with discriminatory and coercive practices aimed at improving the genetic quality of a population. The ethical quandary revolves around concerns of inequality and accessibility, as such genetic enhancements could exacerbate social divides if only available to the wealthy. Moreover, there’s a moral responsibility to consider the long-term consequences of altering the human gene pool, which could have unforeseen effects on future generations.
Second, evidence demonstrates that techniques like CRISPR-Cas9 could be misappropriated for designing pathogens with enhanced virulence or resistance to current treatments. The ease and accessibility of these technologies pose a significant risk, as even individuals with a basic understanding of genetic engineering can manipulate organisms. This situation underscores the urgent need for robust ethical guidelines and stringent international regulations to prevent the misuse of these powerful biotechnological tools. These concerns are echoed in a report by the US National Academy of Sciences, which calls for international cooperation to establish guidelines and oversight mechanisms to prevent the misuse of gene-editing technologies like CRISPR in the development of bioweapons.
The ethical use of CRISPR technology urgently necessitates international cooperation for several compelling reasons. Firstly, the pace at which CRISPR and related technologies are advancing significantly outstrips the development of adequate regulatory frameworks. This gap presents a governance challenge: balancing the need to regulate and monitor the technology without impeding scientific progress and innovation. Given the transnational nature of scientific research, a single country’s policies may prove insufficient in overseeing a technology that knows no borders.
Second, CRISPR’s dual-use potential — here the same technology can be employed for both beneficial (like medical advancements) and detrimental (such as biological weapons) purposes — further complicates the issue. This duality poses significant security risks, making it imperative to develop international norms and agreements that can mitigate the misuse of biotechnology.
Therefore, international cooperation is essential to ensure that CRISPR technology is developed and used ethically, with shared norms and standards that reflect a collective commitment to global security, scientific advancement, and the common good.
Aditya Sinha (X: @adityasinha004) is Officer on Special Duty, Research, Economic Advisory Council to the Prime Minister of India. Views expressed in the above piece are personal and solely those of the author. They do not necessarily reflect News18’s views.
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