Published on 06/02/23
In 2012, Jennifer Doudna and Emmanuelle Charpentier discovered the CRISPR-Cas9 complex that provided the foundation for the modern CRISPR gene editing system. CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats and is a natural process that has long functioned as a bacterial immune system that defended bacteria and archaea from viruses. It essentially kept a record of the numerous viral infections these bacteria and archaea have been exposed to over time. The Cas9 protein was found to be a part of the CRISPR immune system and can locate, cut, and destroy viral DNA. Although there have been generations of researchers studying the CRISPR immune system, it was only in 2012 that Doudna and Charpentier realized that this natural process could be manipulated to engineer genes. They published their results in the 2012 edition of Science. Since then, Doudna and Charpentier won the 2020 Nobel Prize in Chemistry for their groundbreaking research and are now credited as the co-inventors of the CRISPR gene editing technology.
There are 2 components in the CRISPR complex – the Cas9 protein that cuts the DNA, and the guide RNA that can locate the genome sequence. In CRISPR gene editing, scientists identify the sequence in the genome they want to change. A specific guide RNA is then created to recognize the sequence in the DNA. The guide RNA is attached to the Cas9 protein and directs the CRISPR complex to the target cells. Cas9 cuts the target DNA sequence to initiate three main types of genetic edits: disruptions, deletions, and insertions. Disruptions occur when a single cut into the genome sequence is made and the non-homologous end joining results in the addition or deletion of base pairs, leading to disruptions in the original DNA and eventually gene inactivation. A larger fragment of DNA can also be deleted by using two guide RNAs that target separate sites in the process of deletion. Adding a DNA template with the CRISPR system lets the cell correct or insert a new gene as a part of the homology-directed repair.
CRISPR technology has already been implemented in agriculture to give commercially important plants desirable traits, as well as improve yield, plant aesthetics, and disease tolerance. For example, CRISPR-Cas9 has been applied to rice, soybeans, watermelons, citrus fruits, and tomatoes, resulting in a range of beneficial qualities.
The current successful application of CRISPR in plants leads scientists to wonder about the possibilities of using CRISPR in animals and even humans. Using CRISPR in humans could be revolutionary for curing genetic diseases but should be taken slowly with regard to the ethical issues that come with it. During the Second International Summit on Human Genome Editing in 2019, Chinese biophysicist He Jiankui claimed that he had helped produce the first genetically edited babies with the CRISPR system by modifying a key gene in some human embryos for HIV resistance. Jiankui used germline editing, a form of gene editing in embryo, deducing modifications that will later affect every cell of body and be inherited to future generations. The announcement was met with fierce criticism from both scientists and ethicists, deeming the experiment to be premature, irresponsible, and unjustified. Jiankui was sentenced to three years in prison. Though He Jiankui took a faithful leap in the field of genetic engineering, his story remains a warning of the harsh consequences of premature scientific research. With the realization of CRISPR's potential, numerous scientists have begun conducting trials to cure diseases; however, universalization of CRISPR tech in the medical field are still years away from being broadly available to the public.
The newfound possibilities of CRISPR also bring much concern to potential enhancement uses. In essence, this technology could allow parents to choose a newborn’s genetic makeup and ultimately confer genetic superiority. The idea of using CRISPR to achieve enhancement purposes has brought about the discussion of the many ethical implications. For instance, if parents chose for their children to have a talent targeting a specific career path prior to their birth, their children would have their future entirely planned out even before birth. In addition, it may be hard to draw a line between gene editing that should be used for treatment and enhancement purposes. For example, editing genomes to possibly reverse muscle deterioration in the elderly may also attract able athletes who want to outcompete their competitors as such tech might confer them superior muscle function. These purposes of the CRISPR technology could largely be compared to cosmetic surgery, but instead of being something only affecting outer appearances, these germline edits made with CRISPR could be passed down through multiple generations, having the ability to shape the future of humanity.
With its affordable price and quick speed, CRISPR could rewrite the entire genetic code of life and change humankind altogether. In its far-reaching potential, drawing the line between using CRISPR as treatment or enhancement is still a fundamental concern.
References
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Vyas, Kashyap. “Designer Babies: The Controversial Use of CRISPR and Its Ethical Challenges.” Interesting Engineering, Interesting Engineering, 4 July 2019, https://interestingengineering.com/science/designer-babies-gene-editing-and-the-controversial-use-of-crispr.
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