The CRISPR-Cas9 system has revolutionized genetic manipulations and made gene editing simpler, faster and easily accessible to most laboratories.
To its recognition, this year, the French-American duo Emmanuelle Charpentier and Jennifer Doudna have been awarded the prestigious Nobel Prize for chemistry for CRISPR.
Gene editing using CRISPR technology
- The CRISPR is an acronym for Clustered Regularly Interspaced Short Palindromic Repeats, developed in the year 2012
- CRISPR has made gene editing very easy and simple, and at the same time extremely efficient.
- The technology works in a simple way — it locates the specific area in the genetic sequence which has been diagnosed to be the cause of the problem, cuts it out, and replaces it with a new and correct sequence that no longer causes the problem.
- The technology replicates a natural defence mechanism in some bacteria that use a similar method to protect it from virus attacks.
Working of CRISPR
- An RNA molecule is programmed to locate the particular problematic sequence on the DNA strand.
- A special protein called Cas9, often described in popular literature as ‘genetic scissor’, is used to break and remove the problematic sequence.
- A DNA strand, when broken, has a natural tendency to repair itself. But the auto-repair mechanism can lead to the re-growth of a problematic sequence.
- Scientists intervene during this auto-repair process by supplying the desired sequence of genetic codes, which replaces the original sequence.
- It is like cutting a portion of a long zipper somewhere in between and replacing that portion with a fresh segment.
- Because the entire process is programmable, it has remarkable efficiency and has already brought almost miraculous results.
A promising technology for the future: With many Applications
The gene-editing technology has opened up a vast window of opportunity.
- Human health: In the last six years, the tool has enabled scientists to edit human DNA in a dish and early-stage clinical trials are being attempted to use the tool to treat a few diseases, including inherited disorders/diseases and some types of cancer.
- Agricultural productivity: The tool is being extensively used in agriculture. It is being tried out in agriculture primarily to increase plant yield, quality, disease resistance, herbicide resistance and domestication of wild species.
How safe is CRISPR?
- Last year, a study by Stanford University, U.S., found that the CRISPR-Cas9 system introduces unexpected off-target (outside of the intended editing sites) effects in mice.
- There is a growing fear that the CRISPR system is being prematurely rushed for clinical use lingers.
- Some researchers have highlighted that CRISPR-Cas9-edited cells might trigger cancer.
- Another study found that both the mouse and the human gene-edited cells suffered from large DNA deletions far from the intended editing sites.
Issues with CRISPR
The many potential applications of CRISPR technology raise questions about the ethical merits and consequences of tampering with genomes.
1) Ecological dis-equilibrium: An introduced trait could spread beyond the target population to other organisms through crossbreeding. Gene drives could also reduce the genetic diversity of the target population. There is a danger that CRISPR’s affordability and efficiency could run roughshod over long‐standing and valid concerns about the generation and release of GMOs.
2) Threats to species: There is another, potentially much more dangerous and controversial, application of CRISPR, namely to potentially eradicate disease by eradicating disease vectors and invasive species. Such methods could effectively destroy an entire species and could have significant environmental consequences.
3) Germline editing concerns: Making genetic modifications to human embryos and reproductive cells such as sperm and eggs is known as germline editing. Since changes to these cells can be passed on to subsequent generations, using CRISPR technology to make germline edits has raised a number of ethical concerns.
4) Biosafety concerns: It is not unreasonable to think that, in the wrong hands, CRISPR could be used to make dangerous pathogens even more potent. There exist some concerns about the accidental or deliberate release of GE microorganisms or viruses into the environment.
5) Regulatory bypass: Editing the genomes of crops and trees is not new, and debates over the pros and cons of genetically modified (GM) plants have gone on for decades. What makes CRISPR different from other methods of agricultural genetic engineering is that it no longer requires the insertion of foreign DNA into the plant. Hence traditional GM crops/organisms would no longer classify as transgenic.
Ethical concerns
- In November 2018, a Chinese researcher in Shenzen created an international sensation with his claim that he had altered the genes of a human embryo that eventually resulted in the birth of twin baby girls.
- This was the first documented case of a ‘designer babies’ being produced using the new gene-editing tools like CRISPR.
1) Safety
Due to the possibility of off-target effects (edits in the wrong place) and mosaicism (when some cells carry the edit but others do not), safety is of primary concern.
2) Informed Consent
Some people worry that it is impossible to obtain informed consent for germline therapy because the patients affected by the edits are the embryo and future generations. Bioethicists also worry about the possibility of obtaining truly informed consent from prospective parents as long as the risks of germline therapy are unknown.
3) Justice and Equity
As with many new technologies, there is concern that genome editing will only be accessible to the wealthy and will increase existing disparities in access to health care and other interventions. Some worry that taken to its extreme, germline editing could create classes of individuals defined by the quality of their engineered genome.
Regulation in India
- In India, several rules, guidelines, and policies are notified under the Environment Protection Act, 1986 to regulate genetically modified organisms.
- The above Act and the National Ethical Guidelines for Biomedical and Health Research involving human participants, 2017, by the Indian Council of Medical Research (ICMR), and the Biomedical and Health Research Regulation Bill implies regulation of the gene-editing process.
- This is especially so in the usage of its language “modification, deletion or removal of parts of heritable material”.
- However, there is no explicit mention of the term gene editing.
Way forward
- CRISPR technology continues to mature, and existing systems are being engineered to contain innovative capabilities.
- The potential benefits of such revolutionary tools are endless. Currently, this is difficult because many international laws discourage or ban such research and/or inhibit its funding for certain types of investigation.
- Thus, wide spread and reliable data about benefits and risks are unavailable.
- Going forward, many support establishing an organization that will decide how best to address the aforementioned ethical complexities.
- Many countries have advocated for the development of an international and interdisciplinary “global observatory for gene editing.”
- However we must not forget that the risk cannot be justified by the potential benefit.
Conclusion
- Genetic ‘determinism’ holds that the DNA sequence is the prime cause of all human traits, normal and abnormal (health and disease). We should do away with this idea, very first.
- It will take years before the CRISPR system is ready for prime time and clinical use.
- An important issue in its research is that benefits must be greater than risks. Here greater attention needs to be placed on risks, since they may damage living beings or the environment.
- Concerning its regulation, it is time for our policymakers to come up with a specific law or put out guidelines for conducting gene-editing research giving rise to modified organisms.
- The principle of solidarity and consideration of the public good deserve far greater consideration in making sure that these rapid advances become shared benefits for all. This should be our ultimate goal.
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References
https://www.civilsdaily.com/news/nobel-prize-in-chemistry-for-crispr-technology
https://www.embopress.org/doi/full/10.15252/embr.201541337
http://www.bu.edu/khc/files/2018/10/CRISPR-Ethics-reading.pdf
