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Gene editing can help mankind solve many problems, but it can potentially create a host of new ones. Which side of the fence will you sit on?

What do Khan Noonien Singh, Spiderman, Jurassic Park and Blade Runner have in common? Here’s a hint: it has something to do with biology. Krishna Barot has the answer

While seasoned science-fiction cinema viewers may have guessed it, the answer is gene editing. Genome editing, commonly known as gene editing, is a scientific method that enables highly specific changes to the DNA sequence of a living organism – be it bacteria, a plant or an animal. A highly sophisticated and complex method, gene editing engineers certain enzymes to target a specific DNA sequence in a cell, effectively enabling the removal and replacement of the sequence. 

Simply put, the altering of a DNA sequence can trigger significant changes. From changing the colour of one’s eyes to combating diseases such as Sickle Cell Anemia and Tay-Sachs, the immense potential of gene editing has been not only explored but proven to work under the watchful eye of thorough and painstaking research. As newer strides and discoveries continue to be made in this field, it is important to recognize historic moments that paved the path for the study and progression of gene editing.

A Brief History of Gene Editing

The late 1900s were a pivotal period for discoveries in gene editing. Not only did scientists enhance their understanding of genetics, but they also made ground-breaking discoveries that solidified the foundation for the modern-day study and application of gene editing. 

1953 marked the discovery of the “double-helix”, biologically referred to as the twisted ladder-like structure of deoxyribonucleic acid (DNA). This discovery was credited to James Watson and Francis Crick, who in turn owed the discovery to their colleague, Rosalind Franklin. Her work with x-ray diffraction images of DNA proteins pioneered Watson and Crick’s double-helix interpretation. This was followed by multiple exciting discoveries in the field of genetics. Arthur Kornberg pioneered DNA synthesis by actually creating DNA in a test tube, which earned him the coveted Nobel Prize in 1959. The 1960s were a period of intense research, as scientists attempted to further understand subjects such as recombinant DNA, linking DNA fragments together, the defence mechanisms of certain bacterial strains, etc. 

The 1970s onwards was a period of experimentation, as fundamental achievements were made in gene editing. The method of gene splicing was successfully carried out, and experiments in genetic engineering rose considerably in volume and scope. The experiments also aided the application of gene editing studies to real life in the form of vaccines, synthetic insulin, cloning and genetically modified crops. 

It was discovered that a single strand of human DNA is about 2.5 nanometers in diameter. In comparison, a strand of human hair is about 80,000-100,000 nanometers wide. To understand the complexities of something that minute is truly remarkable and to make such colossal advancements within just a few decades is almost incredible. 

With real-world applications such as curing diseases, creating drought-resistant crops to changing the genetic makeup of embryos to produce a ‘designer baby’, it has rightly been viewed with both awe and terror

The CRISPR/Cas9 Breakthrough

One of the most celebrated breakthroughs in gene editing was introduced in 2012 by Jennifer Doudna, Emmanuelle Charpentier and their team, in the form of CRISPR technology. This discovery also earned both scientists the coveted Nobel Prize in Chemistry 2020 “for the development of a method for genome editing” – as per the citation. 

CRISPR is an acronym for Clustered Regularly Interspaced Short Palindromic Repeats; a highly important antiviral mechanism utilized by certain bacterial species. In a 2016 TED Talk, Doudna explained how a simple research project of studying a bacteria’s antiviral defence mechanisms resulted in the honing of CRISPR technology.  CRISPR is a vital component of the bacteria, as it detects and destroys virulent DNA. An integral part of CRISPR is a protein called Cas9 – which seeks, cuts and effectively tears down the virulent DNA. 

Consider CRISPR as a database which holds an extensive record of virulent DNA segments that may have previously attacked the bacteria. These segments are then copied onto an RNA piece, which binds with Cas9. Consider Cas9 as both a tracker and a pair of molecular scissors. It searches for free-floating genetic material in the cell to locate virulent DNA that may have re-entered the bacteria. Upon detection, the Cas9 protein snips and destroys the DNA. 

Emmanuelle Charpentier
Emmanuelle Charpentier — Photo: Emmanuelle Charpentier, Humboldt Foundation

Applying this concept to a laboratory environment allowed scientists to experiment with this mechanism. They also learnt how to repair or rebuild genes which have had DNA segments cut off. This gave rise to methods such as base editing, pioneered by David R. Liu. Base editing converts one DNA base to another without having to cut apart the DNA. This is achieved through base editors, which can be considered molecular pencils. 

CRISPR is known to be the most simple, cheap, precise gene editing technology today. With real-world applications such as curing diseases, creating drought-resistant crops to changing the genetic makeup of embryos to produce a ‘designer baby’, it has rightly been viewed with both awe and terror. 

During the pandemic, CRISPR technology was utilized by the US Food and Drug Administration to authorize rapid COVID-19 tests for the public. The technology’s implementation in a treatment to prevent COVID-19 from attacking lung cells proved to be potentially life-saving, according to a Duke University study. 

However, the technology is not without its limitations. “While we can easily alter the genetic makeup of a cell, we also have to understand that we may create certain organisms that could be more virulent and lethal. This is the flipside,” explained Krishna Vadher, an IB Biology facilitator and academic.  He mentioned how mutations occurring in DNA that has undergone the CRISPR/Cas9 procedure are a topic of concern in the scientific community – as the slightest mutation may lead to disastrous consequences.  Along with that, there are limitations such as off-target edits; an unintended DNA modification that may pose challenges in clinical trials. As research is still being conducted, it has been difficult to implement the CRISPR/Cas9 method to mature cells in large numbers – posing another hurdle for scientists to navigate around. 

Dr Jennifer Doudna — Photo: Christopher Michel

Currently, CRISPR technology is being utilized by various countries, with the USA and China-based companies conducting the most experiments and publishing a high number of studies and articles. Other countries such as Saudi Arabia, India, Turkey and Korea are also pursuing studies and real-life applications of the technology. 

One of the most prominent concerns with CRISPR and gene editing, however,  has nothing to do with biology. Rather, it deals with the ethics of science and technology. 

In gene editing, scientists can edit both somatic cells (cells that make up most of the human body) and gametes (reproductive cells; eggs and sperm)

Ethics in Gene Editing

Ethical concerns apply to all fields of science, be it the effects of nuclear weapons, fossil fuels, or microorganisms on society and the planet. 

Drawing the line between scientific advancements and ethics is a highly tricky decision, and often requires a subjective lens according to Vadher. He explained how aborted fetal tissue is used for HIV/AIDS study, developmental biology and infectious diseases research. Although abortion, in itself, is an extremely controversial subject, the fetal tissue from the surgery facilitates important scientific research. Is there a right or wrong in this matter? There seems to be no concrete answer. 

In gene editing, scientists can edit both somatic cells (cells that make up most of the human body) and gametes (reproductive cells; eggs and sperm). Edits to cells will not only impact an individual but also upcoming generations. While the goal of gene editing will be to enhance desirable traits in individuals, a slight mishap in the form of mutations or off-target editing can result in lifelong repercussions for an individual. 

Fully aware of such implications, both Doudna and Charpentier called for a moratorium (a temporary prohibition of an activity) in the clinical application of CRISPR technology on human embryos. Their call was challenged by certain scientific communities who argued that withholding the application would be unethical, as it prevented them from solving important issues for society’s betterment. 

A massive controversy occurred in 2018 when Chinese scientist He Jiankui claimed to create the world’s first “gene-edited” twins who were resistant to HIV. This invited a slew of legal and ethical concerns, international condemnation and also resulted in Jiankui serving a prison sentence of 3 years. 

Efforts to make processes such as IVF, preimplantation genetic diagnosis and gene therapy (which stem from gene editing) safer and as precise as possible may help scientific communities arrive at an understanding. 

Ethical and moral considerations regarding gene editing on embryos have impacted scientific organizations as well. Many organizations conduct research and experiments on viable and nonviable embryos left over from IVF, or embryos that have been specifically created for research.  “Until there is no viable alternative, scientists will have to utilize such methods for scientific advancements and saving lives,” Vadher added. 

The Future

What we have watched in science-fiction cinema may not be a figment of anyone’s imagination anymore. It may translate into reality. 

CRISPR technology continues to remain relevant in the field of gene editing, as treatments for certain cancers, the engineering of crops that will tackle climate change and improving people’s health and longevity are all being pursued with the help of the technology. 

As CRISPR is a patented technology, several companies have registered for and obtained a license for commercial use. Mammoth Biosciences, a company co-founded by Doudna, is utilizing the technology to create sophisticated disease diagnostic systems. Companies such as Synthetic Genomics are testing the technology to create sustainable energy solutions. Similarly, various industries, from healthcare and agriculture to biotech. 

A report by Allied Market Research states that the gene editing market will be valued at approximately $7.4 billion by 2031, a significant jump from its $3.9 billion valuation at 2021. These projections prove that there is immense potential in the field of gene editing, and the possibilities are unlimited.  

Some people also claim that mankind will soon witness extinct creatures being resurrected – talk about experiencing Jurassic Park for real! However, the scientific community’s priority is solving pressing medical and social issues faced on the planet.

As newer methods such as genetic welding join the gene editing field, the public watches with bated breath, waiting for developments that may impact mankind for generations to come. 

In Star Trek, several of the series explores this very concept – from engineered humans to life forms created for war or servitude… and the question the episodes asked remains relevant today – where do we go from here? 

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