Nobel Prize for CRISPR

 

Dr. Sneha Sinha

 Research Associate, RIS

Two scientists, Emmanuelle Charpentier and Jennifer Doudna were recently awarded Nobel Prize in Chemistry for the development of a gene manipulating technology. Though genetic research has advanced enormously in the last 50 years, the revolutionary ‘Clustered, Regularly Interspaced, Short  Palindromic Repeats’ in association with the Cas9 DNA-cutting enzyme (CRISPR/Cas9 genetic scissors) is ‘one of gene technology’s sharpest tools for re-writing the code of life’.[1] Its discovery can be traced to the efforts of Japanese scientists at Osaka University, who in 1987 noticed an aberrant pattern of DNA sequence, followed by tremendous incremental research. In 2011, these two scientists jointly initiated the investigation of the Cas9 enzyme.[2] CRISPR allows targeted changes in the genetic material by removing, replacing or adding more than one segments of DNA at a time in plants, animals and humans.[3]

There is consensus among scientists about the immense scientific potential of CRISPR, which has revived promises for the future of gene therapy. In comparison with previous gene engineering technologies, CRISPR is easier, quicker, cost-effective, precise and can be used in all living organisms.[4] It has shown promising results for treating diseases and facilitating beneficial agricultural applications. CRISPR can be harnessed in health-care, medicine[5], food, agriculture[6], biofuels and industrial biotech.

 

Though its benefits are immense, CRISPR is seen as a ‘double-edged sword’, increasingly criticised for its potential risks and limitations.[7] Scientists have raised numerous scientific, societal, governance and ethical issues associated with CRISPR.[8] The lack of international consensus about its societal acceptability and safety became strongly evident when a Chinese biophysicist in an effort to make HIV resistant - ‘CRISPR babies’- edited human embryos. CRISPR’s clinical use, while the technology is still emerging, without proper governance and oversight mechanism led to the formation of the International Commission on the Clinical Use of Human Germline Genome Editing convened by the National Academy of Medicine and National Academy of Sciences in U.S., and The Royal Society of London.[9]  In 2018, WHO formed an Expert Advisory Committee on Developing Global Standards for Governance and Oversight of Human Genome Editing to examine scientific, ethical, social and legal challenges associated with both somatic and germ cell human genome editing.[10]

 

The consensus study report on the Heritable Human Genome Editing (HHGE) was prepared through deliberations with 26 academies by 18 experts from 10 countries from all continents (except Antarctica). It recommends ‘no clinical use of gene editing until it has been clearly established that it is possible to make precise and efficient changed without undesired changes’. Its initial use had to be cautious with restricted set of criteria and circumstances. The preclinical requirements should be ensured through national and international governance arrangements before HHGE is approved by any country. CRISPR’s clinical use should only be allowed after its safety issues has been resolved by the researchers, and public too are totally aware of its limitations.[11][12] The report has received diverse reactions from experts of the field.[13]

 

Increasing attention is being paid to CRISPR by public and media, on account of the Nobel Prize awarded to two pioneering scientists for their research on CRISPR. It provides immense potential for agricultural interventions and treatment of diseases in developing economies like India and Africa. Recognising CRISPR’s limitations and ethical issues associated it is essential for developing its regulatory and governance framework.[14]

 

In India, genome editing using CRISPR technology is being applied for disease resistance, herbicide tolerance and increasing the yield of hybrid varieties of rice, which holds promises for the agriculture and food security.[15] Scientists at the Institute of Genomics and Integrative Biology (IGIB) are working towards development and application of CRISPR technology. CSIR’s Sickle Cell Anemia Mission clearly illustrates how CRISPR could translate into medical sciences. The FELUDA test, employing CRISPR technology developed at IGIB is a breakthrough in the COVID-19 detection. It is quicker, accurate and adaptable, and can easily be used at home.[16]

 

The societal and ethical issues associated with CRISPR has to be addressed before its application towards betterment of the society. There is a need to connect science with society to make technology ethical and acceptable, removing people’s perception about its risks. India should also participate in global debates around CRISPR for developing an effective ethical and regulatory framework in India for facilitating research and finding solutions to improve human health.[17]

 

Evolving regulatory and technology governance frameworks, and institutional architecture in India, requires addressing issues of access, affordability, equity, delivery systems apart from its ethics and safety concerns. The experts’ panel discussions and public debates among the stakeholders, both nationally and internationally will be crucial in tackling issues associated with the emerging technologies, like CRISPR.

 

Endnotes

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[1] The Royal Swedish Academy of Sciences press release on the Nobel Prize in Chemistry 2020 available at https://www.nobelprize.org/prizes/chemistry/2020/press-release/.

[2] The historical timeline of key events in the development of CRISPR/Cas-9 can be accessed at https://www.whatisbiotechnology.org/index.php/science/summary/crispr.

[3] The Nature video lucidly illustrates the CRISPR genome editing mechanism available at https://www.youtube.com/watch?v=4YKFw2KZA5o

[4] Hilde, Lovett ‘CRISPR: Five New Debates on Genetic Engineering’ writes ‘why is CRISPR ground-breaking?’. available at  https://teknologiradet.no/en/crispr-five-new-debates-on-genetic-engineering/.

[5] Yang, Li, H., Y., Hong, W. et al. 2020. Applications of Genome Editing Technology in the Targeted Therapy of Human Diseases: Mechanisms, Advances and Prospects. Signal Transduction and Targeted Therapy 5, (1) available at https://www.nature.com/articles/s41392-019-0089-y#citeas.

[6] Zhu, H., Li, C. & Gao, C. 2020. ‘Applications of CRISPR–Cas in Agriculture and Plant Biotechnology. Nature Reviews Moecularl Cell Bioogyl 21, pp. 661–677 available at https://www.nature.com/articles/s41580-020-00288-9#:~:text=CRISPR%E2%80%93Cas%20in%20crop%20upgrade,also%20revolutionized%20current%20breeding%20systems.

[7] Shwartz, Mark. ‘Target, delete, repair - CRISPR is a revolutionary gene-editing tool, but it’s not without risk’ available at https://stanmed.stanford.edu/2018winter/CRISPR-for-gene-editing-is-revolutionary-but-it-comes-with-risks.html.

[8] The applications and limitations of CRISPR technology can be read at  https://www.cbinsights.com/research/what-is-crispr/

[9] Ledford, Heidi. ‘CRISPR babies are still too risky, says an influential panel’ available at https://www.nature.com/articles/d41586-020-02538-4.

[10] Details available at https://www.who.int/ethics/topics/human-genome-editing/committee-members/en/.

[11] Thelma, B. K. Presentation made during the webinar organised by RIS on ‘Nobel Prize on CRISPR’ on 29th October, 2020. She is a Professor at the Department of Genetics, University of Delhi and is a member of the International Commission. She also chaired the panel discussion.

[12] The Commission’s full report can be accessed on https://www.nap.edu/catalog/25665/heritable-human-genome-editing.

[13] For candid reactions of experts see https://www.liebertpub.com/doi/pdf/10.1089/crispr.2020.29106.man.

[14] Chaturvedi, Sachin. 2020. Introductory remarks made during the webinar organised by RIS on ‘Nobel Prize on CRISPR’ on 29th October, 2020. The recorded webinar can be viewed on YouTube.

[15] Reddy, M. K. 2020. Presentation made during the webinar organised by RIS on ‘Nobel Prize on CRISPR’ on 29th October, 2020. He is a Group Leader, Crop Improvement at International Centre for Genetic Engineering and Biotechnology (ICGB), New Delhi.

[16] Chakraborty, Debojyoti. 2020. Presentation made during the webinar organised by RIS on ‘Nobel Prize on CRISPR’ on 29th October, 2020. He is a Senior Scientist, Genome Editing, Stem Cells and Organoid Biology at CSIR-Institute of Genomics and Integrative Biology (IGIB).

[17] Mathur, Roli. 2020. Presentation made during the webinar organised by RIS on ‘Nobel Prize on CRISPR’ on 29th October, 2020. She is Scientist F and Head, ICMR Bio-Ethics Unit.