Behind the Controversial and Forbidden Technique of Gene Editing

Abstract

Gene editing has been one of the biggest names in the biotechnology industry. On the surface, it seems like a tool that can help prevent the anomaly of genetic diseases, however when you dive deeper into it, it is something that can be very unpredictable and can cause abnormal and irregular outcomes in subjects. This technique, classified as forbidden in many parts of the world, is highly controversial and users of such tech have been imprisoned. Many nations around the world are still researching gene editing, so perhaps one day it could be a safe and reliable tool to bring an end to the rise of genetic diseases.

History Behind Gene Editing

To fully understand how the concept of gene editing was first derived, you have to look into its history. Research into genetics started in the 1950s and 1960s; discoveries in this time period paved the way for future study of genetics and biotechnology

It all started from the discovery of the double helix structure of DNA in 1953 by scientists James Watson and Francis Crick, based on the work of their colleague Rosalind Franklin. The discovery of the double helix structure was an important moment in the history of innovation in the field of genetics. It was followed by the first isolation of DNA in a test tube in 1958 by scientist Arthut Kornberg. He isolated DNA polymerase from bacterial extracts and within a year he was able to successfully synthesize DNA in vitro for the first time.

Leading into the 1960s, genetic engineering innovation shifted to Silicon Valley in 1962 through the work of scientist Osamu Shimomura and researchers Martin Chalfie and Roger Tsien. The gene coding for the green fluorescent protein (GFP) present in Aequorea Victoria jellyfish was successfully fused with another gene that produces the protein of interest (POI). This allowed researchers to track which cells produced that POI as the GFP protein when exposed to blue wavelength glows. This revealed the location of the POI, thus allowing the tracking of it in cells.

Following this, the discovery of DNA ligase in 1967 was a pivotal point in molecular biology since DNA ligase is essential for the repair and replication of DNA in all organisms, which is what gene editing is based on. This was soon followed by the discovery of restriction enzymes which identify and cut foreign DNA.

It wasn’t until the 1970s though that genetic engineering took off. Throughout the 1970s, Paul Berg accomplished creating recombinant DNA from more than one species, this became known as the “cut and splice” technique. DNA was cut from 2 viruses creating sticky ends, then the DNA was incubated, the ends would anneal on their own, and the addition of DNA ligase would seal the sticky ends together. This period of time formed the understanding of how restriction enzymes cut DNA, and how host DNA works to protect itself is the basis for the modern genetic engineering therapies that are being developed, for example CRISPR which we will dive deeper into in this article.

Innovation and Controversy Behind CRISPR Gene Editing

CRISPR gene editing is based on the CRISPR-Cas systems, such as CRISPR-Cas9. These are adaptive immune response systems that protect prokaryotes from bacteriophages. They work by splitting the nucleic acids of invading bacteriophages such as viruses, thus protecting prokaryotes from viral infections. Over time the use of CRISPR-Cas9 turned to gene editing. This technique was thrust into the spotlight in 2012 when George Church, Jennifer Doudna, Emmanuelle Charpentier, and Feng Zhang modified targeted regions of genomes using gene editing

CRISPR stands for clustered regularly interspaced short palindromic repeats, which are repeating DNA sequences in the genomes of prokaryotes. They were first identified in the bacteria E.coli in 1987. When these CRISPR systems were first discovered they were only thought to have applications in repairing DNA in prokaryotes to create defense mechanisms against bacteriophages. However in 2012, the same scientists discovered that by designing “guide” RNA, a specific region in a genome could be targeted. It was found that the CRISPR-Cas9 system could be used as a cut and paste tool to modify genomes. This system could be used to introduce new genes, and even remove old genes. It could also be used to activate and silence genes.

CRISPR-Cas9 has been used to switch off genes that limit the production of lipids in microalgae, leading to increased lipid production and higher yields of biofuel. This technique has the ability in the near future to even cure genetic disorders such as sickle-cell anemia and cystic fibrosis. There is already a wide range of applications of CRISPR-Cas9 in diseases such as cancer.

Even though this system has lots of positive and revolutionary applications in the field of healthcare, there is still a lot of controversy related to the system’s ethicalness surrounding it. One of the controversies around CRISPR is based around the fact that this new technology is powerful and very vulnerable to misuse. For example, Chinese scientist He Jiankui announced that he had genetically modified twins before birth using CRISPR which made them resistant to HIV, resulting in a three year imprisonment. The effects of such technology are far too uncertain and should not be used to make heritable changes to a human’s DNA, though non-heritable changes could be argued for. This method was also known to be medically unnecessary as there were already much safer and certain methods to prevent certain diseases. So given gene editing’s unpredictable and unknown effects it is logical and ethical to be wary of it.

Why is CRISPR Gene Editing Forbidden + Discussion

So why is this revolutionary technique forbidden throughout the world? The main reason for this is simply that the technique is too risky in embryos targeted for implantation. The technology would still only be permitted for certain circumstances even if it ever gets approved.
Although CRISPR can precisely edit the genome of an individual, it has been seen that many unwanted changes have occurred in the genes of the subject which resulted in many unpredictable outcomes among the cells in the embryo. So the question stands, is this method of gene editing necessary? Is it an ethical solution to preventing genetic diseases despite its uncertainty and unpredictability? These questions are the exact roadblocks on the journey to the future of gene editing.

References

“Full Stack Genome Engineering.” Synthego, https://www.synthego.com/learn/genome-engineering-history#:~:text=1970s%3A%20Genetic%20Engineering%20Takes%20Off,genetics%20for%20all%20future%20scientists.

Ng, Written by Daphne. “A Brief History of CRISPR-Cas9 Genome-Editing Tools.” Bitesize Bio, 29 Apr. 2021, https://bitesizebio.com/47927/history-crispr/.

Hunt, Katie. “What Is CRISPR and Why Is It Controversial?” CNN, Cable News Network, 7 Oct. 2020, https://www.cnn.com/2020/10/07/health/what-is-crispr-explainer-scn-trnd/index.html.

Human Germline and Heritable Genome Editing: The Global Policy … https://www.liebertpub.com/doi/10.1089/crispr.2020.0082.
Ledford, Heidi. “’CRISPR Babies’ Are Still Too Risky, Says Influential Panel.” Nature News, Nature Publishing Group, 3 Sept. 2020, https://www.nature.com/articles/d41586-020-02538-4#:~:text=Editing%20genes%20in%20human%20embryos,a%20high%2Dprofile%20international%20commission.

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