CRISPR/CAS9 has brought the field of medicine, research, and cell therapy to a turning point. A new set of doors have opened, enabling scientists and researchers to discover new possibilities within the genetic field — the very basis of all organisms. The CRISPR gene editing tool has endless applications, ranging from turning genes on and off to altering a gene, completely changing the face of medicine — ultimately changing the world.
Though researchers Dr. Jennifer Doudna and Dr. Emmanuelle Charpentier received the 2020 Nobel prize for their efforts in CRISPR, researchers dating back to 1993 have contributed greatly towards this award winning technology. Dr. Francisco Mojica, a molecular biologist of the University of Alicante, Spain, discovered the very roots of CRISPR technology — that a bacteria’s DNA repeats and that the DNA of a virus will always match what it is attacking. Since then, researchers from across the globe have been making astonishing contributions to both CRISPR technology and the genetics field. Mojica and multiple other researchers discovered the various fundamentals for the CRISPR technology, and Daudna and Charpentier created the newest, most precise, and efficient biochemical CRISPR mechanism.
From Science Fiction to Reality
Ever since the double helical structure was discovered, in the 1950s, the door to modern biology had opened. For the first time, scientists were able to understand the chemistry and makings of the very basis of all life on Earth. This led to a series of questions and experiments; such as, what genes are responsible for certain human diseases, or traits? The enticing ability to tinker and map out the DNA sequencing sparked curiosity to many geneticists. When we search for “gene editing technology”, the top searches are all about CRISPR, however, for decades, researchers have been conducting experiments and creating gene editing/mapping technologies. The first gene to be mapped was for Huntington’s disease in 1983, coincedently, during the same time and place (Massachusetts General Hospital) as where Jennifer Doudna was doing her graduate work.
What is CRISPR/Cas9?
There are two main parts to this technology, CRISPR and CAS9, both adapted from a naturally occurring gene editing mechanism in bacteria. CRISPR, the repeats, are found throughout a bacteria’s DNA. Bacteria stores a bad virus’ DNA in order to identify the virus for future circumstances. Scientists create a short RNA sequence to “guide” the CAS9 enzyme to the specific DNA bases. CAS9 then works as a pair of scissors and cuts the DNA at the targeted location. Once the unwanted DNA bases are gone, either the scientist will let the DNA use it’s own repair machinery, or they will replace it with a customized DNA sequence.
Essentially, any sequence of DNA can be altered, leading to a series of prolonged discussions and serious ethical concerns. For families struggling with treating their incurable sick child, this technology brings hope of editing the brutal mutations from their gene pool. However, for those living in poverty, this is just another way for the wealth gap to get wider. As CRISPR can target any DNA sequence, the burning question is, where do we draw the line between treating diseases and enhancements?
Heated Debates on Ethics
A few years ago, in November of 2018, Chinese biophysics researcher Dr. He Jainkui announced his successful implementation of CRISPR technology to the medical community. It all started when Jaikui took on a daring medical experiment, where he asked couples affected by HIV with infertility problems to partake. It was supposed to use IVF (In Vitro Fertilization) to extract the HIV infected sperm before insemination. Then a reliable procedure of sperm washing would have been done to remove the virus. Instead, without proper paperwork and supervision, Jainkui managed to use CRISPR gene editing technology to “cut” out the HIV mutations from twin embryos; both CRISPR babies were successfully brought to term — Lulu and Nana. Though it was successful, the response from both the majority of the medical community and the Chinese government was of loud opposition. The most striking part of this experimental procedure was that the gene editing was done on the germline — many ethical debates either stem off of technology or advancements that involve the germline or enhancements. As there was a moratorium for the first gene editing research in 1974, scientists are calling for another one on such experiments; but since this could slow or prevent genetic engineering research, scientists are siding in favor of Jainkui.
Gene editing technologies have been prevalent for some time now, but none of them were as efficient, timely, “easy”, or cost efficient as CRISPR technology. Due to this, accessibility has also increased and become more widespread. The main concern here is, with technologies that are relatively easy to use (like CRISPR), how do the scientists regulate themselves? Although they have used their tools for good, it is important that this technology does not end up in the wrong hands.
If a technology with endless applications —whether moral or not — becomes available to anyone, how will bioethicists prevent CRISPR from being used to alter genes for the sole reason to be more “desirable”? Even if it is regulated, we already have an example of how Jaikui used it without approval.
Based on the cost of various gene therapies and gene editing technologies, the average cost is over 2 million dollars, an insanely high number! We now have technology to save lives, but how is anyone supposed to afford it? As these are fairly new advancements, most insurance companies do not cover it either. Every enhancing technology is bringing us closer to making eugenics prevalent again, and since only those who have that much financial comfort can use them, without regulations, we are bound to enter an era where the gap between lower and upper class will become wider and they will be renamed as the “undesirable” and “desirable” class.
Methods for having a “desired” baby are already in place. Preimplantation Genetic Diagnosis allows couples to select a viable egg for IVF. This doesn’t involve any gene editing, but it allows for choosing a set of DNA that will be more “desirable” or “fit”. But with gene editing, discussions on “designer babies” are prevalent. You want your child to have blue eyes? Edit their genes. How about more muscle mass? Edit their genes. Our DNA makes up every single aspect of our physical, mental and emotional state, and CRISPR/Cas9 technology can change/modify anything.
Gene editing has many ethical considerations, however this is a significant turning point for many other aspects of biology as well. In 2019, Qihan Bio, a Chinese company, announced that they had used CRISPR/Cas9 gene editing technology to genetically modify a pig’s DNA to create organs that have a higher safety and success rate for human transplants. Pigs create their own unique molecules that set off the human immune system, promoting rejection; with more sustainable organs, rejection rates will decrease and availability will increase.
We also see many biomedical technologies used in agriculture. Many technologies that enhance human life and development have the benefit of living longer. With that and the exponential growth of the global population, the agriculture industry has an obligation to enhance its abilities.The first use of CRISPR/Cas9 in agriculture was in the tomato plant. Modifications to the genome were made to increase sustainability, quality, and quantity. However, as with any new enhancement, there is public fear and it is in the hands of the government and public health committee to determine whether such crops should be implemented.
Here Comes the Sequel – Base Editing!
Advancements in genome editing continue to become increasingly efficient and precise. New research on Base Editing allows for a significantly higher percent of accuracy, as it involves the precise alteration of the mutated base pair. This new approach to gene editing has been proven successful in treating genetic diseases such as sickle cell disease and beta-thalassemia. This shows that the exploration of CRISPR’s capabilities and its derivatives has just begun. The CRISPR train is about to leave the station and the scientific community may have very little time to debate if they should board the train or not…..
References
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