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Mihret Girum

Resistance to HIV via CRISPR

We live in a time where scientific advancements and discoveries are being made faster than ever. All over the world, people are researching and testing different ways that we can utilize the skills and information we have acquired to cure epidemics and diseases that trouble humanity. In most instances, we accomplish this using model organisms which are good indications of how humans might respond to developing treatments while maintaining the ethics of science.

But what if someone prematurely decided to test a scientific breakthrough on humans?

He Jiankui, is an associate professor at the Southern University of Science and Technology in Shenzen, China. On Wednesday, November 28, 2018, Jiankui presented his “success” in creating the world’s first genetically modified babies at the Second International Summit on Human Genome Editing. His accomplishments were met with the questions and concerns of many fellow scientists at the summit and abroad due to his experimentation on the germ line of a human using a technique that to many is not clear to work without side effects.

Jiankui used Crispr-Cas9 to edit the CCR5 gene which is a gene involved in the immune response but is also known to be a co-receptor for HIV to enter host cells. Mutations of this gene have been correlated with HIV resistance and thus Jiankui decided to use this principle to produce HIV resistant embryos from an HIV-positive father and an HIV-negative mother. (1)

A key detail that many fellow scientists brought up during the summit was that the lack of medical need to edit the genes of these particular children. This was because HIV can only be transmitted from the mother through the direct contact of bodily fluids. In this instance, Jiankui used HIV-negative mothers for his trials and therefore the embryos were at no risk of acquiring HIV.

Another concern was of the use of Crispr-Cas9; most of us have had an introduction to the mechanism of CRISPR-Cas9 through taking some of our introductory Biology courses but here’s a brief recap:

CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats, and it is a system that can be programmed to target very specific sequences in our genome and further assist in the editing of DNA at specific locations. It works by using CRISPR sequences that can be transcribed into RNA sequences which guide the system to bind to precise locations of the DNA. Once bound the Cas9 enzyme can cut the DNA at that location and deactivating the expression of that gene. The discovery of the application of this technology to genome editing in 2013 created endless possibilities for the field of human genome editing and potentially discovering ways to cure diseases.

Although the discovery of how we can use this system is amazing, recent studies have been discovering that CRISPR while targeting the genes it is specified for also produces unexpected insertions and deletions as a result of imprecision of DNA repair mechanisms when piecing the broken strands of DNA back together. (2) This may have unexpected far reaching results on the human body that scientists do not expect and are unable to control.

One of the last major concerns raised by many were the ethics of the process. Although the intentions of Jiankui perhaps were to improve the quality of life for these children and their future offspring, many believe that several ethical issues were overlooked by Jiankui and his team. During the Summit, many raised question of how he would ensure that these children were safe from the side effects of CRISPR and how he justified this experiment. The question of ethics is often difficult to address and can be quite subjective at times but to attempt to lessen its contribution efforts are being made to create a set of regulations to follow in the future for research pursuits such as these.

If you are interested in learning more about Ethics in the context of biology and the medical field, Philosophy 313 is a thought-provoking course at the U of C that allows you to freely explore and discuss controversial topics such as these.

Due to Jiankui’s “lack of transparency” when proceeding with his trials, many feel that he was hasty in employing this technique on editing the human germ line. Although Crispr-Cas9 is a method that has great potential, much more extensive research is required before we can confidently use it to treat humans. His presentation to the Second International Summit on Human Genome Editing has been a polarizing topic in the scientific community and has opened the minds of many to the potential for research on humans and what the boundaries are.

Let us know what you think!

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