• Shalini Guleria

The Narrative Around Gene Editing Needs to Become Smarter


CRISPR – Gene Editing

Much like editing a photo on Instagram, or editing a word document, we now have the requisite technology to edit DNA, and fundamentally alter imperfections. While it all sounds complex, the methodology is actually pretty straightforward. Just like a programme needs a set of instructions to run – ‘a code’ – similarly, human cells need a code to perform vital functions. This code is known as DNA (deoxyribose nucleic acid). At the fundamental level, every living organism on the planet possess DNA of one form or another. Human DNA molecules are composed of two chains coiled around each other, resulting in a double helix shape. Nearly every cell in an individual’s body has the same DNA, which itself can be found in the cell nucleus. Genetic instructions, used in the growth, development, functioning and reproduction, of all living organisms and many viruses, are located in this helix. By its very nature, DNA is passed on from one generation to the next – forming the heredity material in humans.


Understanding DNA

Information is stored in the DNA in the form of four chemical bases, with varying permutations and combinations of these four providing different information – adenine (A), guanine (G), cytosine (C) and thymine (T). The human DNA comprises of approximately 3 billion bases and more than 99% of those are the same in all people. The order or sequence of these bases determines the information available for building and maintaining an organism, hence providing a unique genetic makeup to each individual. At the time of reproduction, cells are replicated. At this time, DNA replicates itself, with each DNA strand serving as a template for duplicating the sequence of bases – in this way, information can be passed from one generation to another. The process of DNA replication is facilitated by RNA, which is another biological molecule similar to DNA. RNA provides a a template for the replication of DNA strands. It also plays a major role in catalysing like controlling gene expression, or sensing and communicating responses to cellular signals.


Inheriting the Code

A gene is the basic physical and functional unit of heredity – in practice, it is made up of several DNA molecules containing information that flows from one generation to another. This information influences everything from similarity in the outward physical features of the parents and offspring, to intrinsic qualities, such as blood types. In humans, genes vary in size, depending on the number of base combinations of DNA in them. An offspring inherits two copies of each gene – one from each parent. While most genes are same in every individual – resulting in the similarity of features in the same species say, humans. A small number of genes (less than 1% of the total) vary from person to person. This is in keeping with the notion that no biochemical reaction is completely reliable, unlike the chemical reactions we see in labs. The slight variations in each gene, referred to as alleles, are what contribute to unique physical features – such as differing facial makeup.


The Human Genome Project, which is working to identify all the genes to specific purposes, estimates that humans have between 20,000 to 25,000 genes. Despite being astonishingly successful at working and repairing itself, the human body can allow errors in the genetic code to be passed on. This causes inheritance of a genetic disorder, manifesting itself as bodily mutations, sensory impediments, or even unusual functioning of the brain. We know these disorders as cystic fibrosis, downs syndrome, sickle cell anaemia etc. Because they are coded in an individual at the fundamental level, only the symptoms of these diseases can be managed – that too, only to varying degrees. Curing them has until now been impossible. This is where Gene Editing comes into play.


Cracking the Code

Genome editing is an umbrella term, used to define a group of technologies that gives scientists the ability to alter an organism’s DNA. Theoretically, they can allow all genes to be modified by the addition, removal, or even modification of specific strands of at desired locations. This then alters the gene, which is made up of those DNA. Furthermore, since genetic material is transferred hereditarily, altering genetic material in one organism will lead to a change in the entire gene pool. Consider, introducing an extermination gene in some female anopheles mosquito – responsible for the transmission of malaria – and given their reproduction rate, wiping out the entire species in a few months. This precise application is being attempted in Africa, with the help of the Bill and Melinda Gates Foundation.


Several approaches to genome editing have been developed, such as gene therapy, gene targeting etc. A recent technique, and one that has gained most currency, is CRISPR-Cas9. Short for Clustered Regularly Interspaced Short Palindromic Repeats – and the associated Protein 9 – CRISPR is a quick and relatively inexpensive technique. It has been adapted from a naturally occurring genome editing system found in bacteria. In nature, bacteria capture samples of DNA from invading viruses and use them to uniquely recognise each invading virus. Then, the memory of this identification is saved in, what scientists call CRISPR arrays. The next time the bacteria is attacked by the same virus, it produces RNA segments from these CRISPR arrays, which target the viruses’ DNA. In this process, the bacteria uses Cas9, or similar enzyme, to cut the DNA apart, which disables the virus. Effectively therefore, the bacteria takes a sample of the DNA, uses RNA to identify it, and when a repeat attack takes place, it uses Cas9 to edit the DNA sample in a manner that disables the virus, then using it on the invading population.


When duplicated in the lab the CRISPR-Cas9 system works quite similarly. Scientists create a small piece of RNA with a short guide sequence that binds to a specific target sequence of DNA in a genome. The RNA also binds to the Cas9 enzyme. As observed in the bacteria, the modified RNA is used to identify the DNA sequence, and the Cas9 enzyme acts as a scissor and cuts the DNA at the targeted location. Once the DNA is cut, the bases are exposed, and the scientists use the cell’s own DNA repairing machinery to add or delete pieces of the genetic material or to make certain alteration to a DNA segment.


This technique has great applications for genome editing, and a huge potential in the prevention and treatment of diseases. While currently it is only being used in cells and animal models, the potential is limitless. A team funded by the Bill and Melinda Gates Foundation is attempting to use Gene Editing to end malaria. They seek to accomplish this by rendering the female anopheles mosquito infertile, dramatically reducing the population and throttling the spread of the disease. Despite the threat of upending the madly convoluted symbiosis in our ecosystems, the threat from wiping out female anopheles is limited – and, ending malaria is largely uncontroversial.


What does court controversy is gene editing in humans. Genetically engineered humans have been the subject of numerous science fiction stories – from geniuses, to super strength. This raises ethical questions, what if the rich could guarantee seats at Harvard for their kids even before they were born? Should we as humans be allowed to define what future generations look like? If so, how are we any different from Hitler who wanted blue-eyed Aryans alone? If strength or perspicacity can be engineered, what happens to the rest of us who haven’t been engineered in that way? What happens to the differently-abled? How do we prevent existing inequalities from getting entrenched in a genetically engineered universe where the rich can pay for better-looking, smarter, and stronger kids? What sort of a society will it even be?


Just look at the recent case from China. When He Jainkui announced that he had successfully altered the genes of two human babies at conception, so as to prevent them from being infected by AIDS virus, the bulk of media reacted with typical mindless sensationalism. ‘Is this the start of a terrifying new chapter in gene editing?’, read a headline by Vox. No one seemed to question if the family was adequately made aware of the risks, or if peers had reviewed the possibility of irreversibly mutating the HIV disease into something more dangerous – and passing it on to future generations. Even today, despite the blatant disregard of regulations by a Chinese scientist, there is little discussion around the seemingly cavalier manner in which the Chinese – egged on by the Communist Regime – are conducting research in the field. There is little oversight of Chinese experiments, or what happens to the animal or human subjects on whom research is conducted. It is unclear if animals particularly are constrained from entering the normal ecological chain, where they could otherwise reproduce and cause significant harm, including making diseases themselves more resistant to treatment.



Such verbosity obfuscates a certain nervousness, and scepticism about the potential applications of the technology. It is also a reflection of the fact that we have allowed the narrative of gene editing to be guided by science fiction, conspiracy peddlers, and sensationalists in the media. It also does more harm than good – often giving credence to demands for a ban on research. In truth however, gene editing is not even close to achieving any of the possibilities mentioned above. Biology works in ways that even experts don’t understand completely, so its possible that we might never have the technology to engineer super strength or intellect. However, gene editing does hold the potential for something more benign, and it has demonstrated the same.


Among these benign applications are treatment of chronic diseases like Cancer, HIV, Down Syndrome, Parkinson’s Disease, and Autism, among others. There is some serious research ongoing to this end. It is important for the sake of humanity that we allow that research to continue, and not give in to the temptation of sensationalising a technology that we know so little about. At the same time, it is important to stay vigilant about any possible applications that have such ethical ramifications, but neither can be accomplished if we are blinded by sensationalism. Biotechnology experts, ethicists, lawyers, and civil society will have to work together to ensure that research in this sector proceeds to alleviate human concerns, and no one should be offered an avenue to profit from misleading information. If gene editing succeeds for the right reasons, humanity would have secured a future where people would not have to suffer needlessly – that, should be our primary objective.


References

https://ghr.nlm.nih.gov/primer/genomicresearch/genomeediting

https://en.wikipedia.org/wiki/CRISPR

https://www.neb.com/tools-and-resources/feature-articles/crispr-cas9-and-targeted-genome-editing-a-new-era-in-molecular-biology

https://www.livescience.com/58790-crispr-explained.html

https://www.livescience.com/60938-a-breathtaking-new-gif-shows-crispr-chewing-up-dna.html

https://www.britannica.com/science/gene-editing


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About the Author

Shalini Guleria is currently pursuing her Masters in Tissue Engineering where her research is focused on developing better treatment and detection techniques for Cancer. She is presently associated with Scion Research, New Zealand and holds a Bachelor's Degree in Chemical and Biological Engineering from the University of Waikato, New Zealand. Shalini has won two consecutive national awards at the prestigious Sir Paul Callaghan Eureka Awards for engineers and scientists. Apart from sciences, she is also a highly talented artist.

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