GS Paper III

News Excerpt:

Recently, Casgevy and Lyfgenia, the two cell-based gene therapies (utilising the CRISPR/Cas 9 genome editing technology) were approved by the Food and Drug Administration (FDA, USA) for sickle cell anemia treatment and beta-thalassemia.

About the CRISPR/Cas 9 technology:

• Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), a feature of the bacterial immune system, forms the basis for this technology. 
• In a nutshell, the system in bacteria serves as a warehouse for past infections by storing a part of the viral genetic material and incorporating it into its own, so the next time it is attacked, the bacteria is capable of recognising the virus and destroying it. 
• The bacteria, in short, is immunised when it employs the CRISPR system.
• Researchers adapted this immune defense system to edit DNA. They create a small piece of RNA with a short "guide" sequence that attaches (binds) to a specific target sequence in a cell's DNA, much like the RNA segments bacteria produce from the CRISPR array. 
• This guide RNA also attaches to the Cas9 enzyme. When introduced into cells, the guide RNA recognizes the intended DNA sequence, and the Cas9 enzyme cuts the DNA at the targeted location, mirroring the process in bacteria.
• The CRISPR-Cas system is effective and easy to manipulate. 
• It has been utilized as a tool to cut, delete, or add DNA sequences at precise locations by scientists and researchers.
• Thus it opens different windows to treat genetic disorders, develop drought-resistant plants, modify food crops, or even experiment with de-extinction projects involving the woolly mammoth and the dodo.

Indian Regulations on CRISPR technology:

• The decision-making process for CRISPR research is governed by the existing legal and regulatory framework in the country.
• The New Drugs and Clinical Trials Rules (2019) classify Gene Therapy Products (GTPs), including those developed through CRISPR, as new drugs, subjecting them to a thorough approval process by the Central Drugs Standard Control Organization (CDSCO). 
• Additional requirements will be determined following the ICMR-DBT (Dept of Bio-Tech) National guidelines for GTPs and oversight by bodies such as the Review Committee on Genetic Manipulation (RCGM) and the Genetic Engineering Approval Committee (GEAC).
• All biomedical and health research in India must adhere to the ICMR National Ethical Guidelines for Biomedical and Health Research Involving Human Participants, 2017.

Germline Editing and use of CRISPR, An Ethical Dilemma:

• Apart from the health equity and disparities associated with CRISPR, one of the biggest controversies has been about germline editing. 
• Most of the scientific community supports the use of CRISPR to treat monogenic (involving or controlled by a single gene) diseases. 
• Germline editing is heritable and more complex and begs the question if it is even moral to subject an individual to heritable changes, even if it is to treat debilitating genetic conditions.
• • Germline: refers to the sex cells (eggs and sperm) that sexually reproducing organisms use to pass on their genomes from one generation to the next (parents to offspring). Germ lines are the link between generations.
• Presently, genome editing is restricted to somatic cells and there is a ban on germline editing. 
• Most countries including India have forbidden genome editing in human embryos through legal instruments or through guidelines. 
  • In India every Institution involved in biomedical research is required to follow ICMR National Ethical Guidelines and register with the ethics committee which monitors research (including around gene editing).
• The gene editing technology has also raised concerns regarding it becoming a commodity that wealthy parents will exploit to improve the fate of their children not only for therapeutic purposes but for genetic enhancement.

What must be done:

• Institutions undertaking cutting-edge research must come up with best practices in community engagement, education, and timely and truthful communication to build trust among all stakeholders with a special focus on communities.
• CRISPR is a tool whose utility is determined by how humans utilise it. 
• Ethics must be at the fore, because even if there is scientific success, societal acceptance cannot be guaranteed. 
• There needs to be enough commitment to integrate ethics in research work for the technology to have a positive impact.
• The use of CRISPR Cas must be justified on the legal and bioethical principles, and these principles should protect human dignity, safeguard the integrity of the patient, and safeguard the content of their genetic information to avoid inappropriate uses. 
• Together, bioethics and legal law will have to work together to regulate the use of patient information, protecting fundamental rights, such as health. Considering that these techniques must be carefully evaluated and observed, 

Way Forward: 

The rapid advancement of CRISPR technology necessitates a balanced approach integrating ethical considerations and legal frameworks. By prioritizing community engagement, education, and transparent communication, coupled with stringent regulations, we can ensure the responsible and equitable application of CRISPR for the betterment of society.