Imagine being alive in the ’80s and learning that in the future, most of our lives will depend on computers. The thought of shopping, dating, and staying connected through computers for day-to-day communication, was a bizarre thought for that time. No one ever imagined that we would be holding a device no bigger than our palm, that will basically be able to solve our everyday inconveniences. But then, all of this happened and science fiction became a reality.
Today, genetic engineering is at a similar point. Ever since the discovery of the structure of DNA, back in the 1950s, scientists have been trying to tinker with it. This was one of the early milestones in genetic study, which defined genetics, as we know it today. This milestone became the backbone of all future discoveries that the world of biology has seen. In the 1970s, scientists inserted snippets of DNA in bacteria, plants, and animals, to both, study and alter them for research, medicine, and agriculture. The first-ever genetically modified animal was born in 1974, making mice the standard tool for research. Today, we can synthesise so many chemicals and medicines by genetically engineering life, rather than harvesting the necessary materials from the organs of animals. Life-saving clotting factors, insulin, and growth hormones are all a result of this process. Scientists also altered the DNA of a tomato, giving it a longer shelf-life than a regular tomato.
The 1990s saw a brief swoop into human engineering. Babies were made in such a way that they carried genes from 3 humans, to treat maternal infertility. Science has come a long way since then, and today we can see super-muscled pigs, featherless chickens, see-through frogs, and even glow-in-the-dark fish! Up until recently, gene-editing was extremely expensive, complicated, and time-consuming. This has now changed because of a revolutionary technology discovered, known as CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats). This discovery has extensively reduced the cost of engineering overnight.
How Does Genome Editing Work?
Genome editing involves a process where an organism’s genetic code is modified. Scientists use enzymes to ‘cut’ the DNA, creating a double-strand break or DSP. DSP occurs by either Non-Homologous End Joining (NHEJ) or Homology-Directed Repair (HDR). NHEJ uses the gene knockout method, while HDR uses additional DNA to create the desired sequence within the gene, also known as gene knock-in.
CRISPR-Cas9 Used for Ground-Breaking Discoveries
CRISPR is a simple yet very powerful system for editing the genes of organisms. Since 2012, this system has been used extensively for academic research, drug development, diagnostics, and agriculture. CRISPR is an adaptive immune system used by microbes in living organisms. It creates a defence mechanism against invading viruses. They counter-attack the viruses by recording and targeting their DNA sequences. In nature, CRISPR plays a very important role in the microbial community. When an invader or a virus attacks the microbial cell, they deploy a CRISPR-associated nuclease (CAS9) to chop off a part of the virus’s DNA. The cut-off DNA fragment will then be stored between the palindromic CRISPR sequences to memorise the sequence for future attacks from the same virus.
Since the scientists have discovered how the CRISPR system worked in bacteria, they figured out how to reprogramme it to allow gene-editing in any species. The technique has been repurposed into a simpler one that scientists use today, to edit genes in living organisms, including the genomes of mammals. In recent years, CRISPR has been swiftly adopted for creating complex animal genome changes, turning specific genes on or off, and genetically modifying plants. This technology has created a revolution and is being used in thousands of labs worldwide!
In 2015, Bertie, the first-ever, gene-edited cow was born in Iowa, US, and the genius behind it is a gene-editor named Dan Carlson. He was working on a problem that has been bothering farmers for generations — dehorning cows. This is a very painful process for dairy cattle and a very disturbing one for the farmers to put their animals through it. Carlson wanted to save these cows from the pain of dehorning by making sure that they are born without horns. Carlson’s team took a dairy cow’s cell and cut up the genetic segment that makes the animal grow horns. Then, they swapped in a sequence of DNA with that of a beef cattle, making them hornless. In the next step, the team created an embryo from the edited cell and put it inside a surrogate mother cow. Nine months later, Bertie, the hornless cow was born. Bertie then became a father to 6 calves, all of them inherited the no-horn gene.
In 2018, a Chinese scientist named He Jiankui claimed to have altered embryos using CRISPR in a bid to make them immune to HIV. After he dropped the bombshell to the world about the gene-edited twin girls, he also revealed the existence of another pregnancy involving a gene-edited baby. However, he was bombarded with a lot of questions and criticisms, most of them based on his claims about them being actually immune to the virus or based on the ethical considerations of editing the genomes of a human embryo. Recently, Jiankui, along with 2 others were sentenced to 3 years in jail for ‘illegally carrying out human embryo gene-editing, intended for reproduction.’ The court also found out that Jiankui forged documents to slip past his ethical review. He also fabricated information so that the doctors could unknowingly implant the gene-edited embryos into two women.
Why the Setback?
CRISPR has unprecedented potential to create a revolution in science in the future. It has also proved to outperform the traditional gene-editing techniques, like Transcription Activator-Like Effector Nucleases (TALENs) and Zinc Finger Nucleases (ZNFs). However, there are many safety and ethics concerns raised by institutions and people worldwide. One of the major problems in gene-editing is that genome study is still at the infancy stage. Many scientists fear that this technology still needs a lot of work and accuracy to make sure that changes made in one part of the genome don’t affect any other functions in the body. This is a very important issue when it comes to using this technology, especially for human gene-editing. Another issue is that, once this technology is used in any plant or insect, it might be difficult to distinguish from the naturally occuring version of it and if released in the environment, and could seriously affect biodiversity.
Policymakers are continuously debating on what limitations to put on the technology. In April 2015, the US National Institutes of Health issued a statement that it will not fund any research that uses gene-editing tools like CRISPR in human embryos. While across the ocean, the UK’s Human Fertilisation and Embryology Authority indicated that CRISPR-Cas9 can be used on human-animal hybrid embryos under 14 days old. Even though the technology claims to have a base for ground-breaking discoveries in the future, the debate relating to the ethical and safety-related concerns may be slowing down the process.
What Does the Future Hold?
The ongoing development of CRISPR will certainly be used to further our understanding of human developmental programs, whether in human embryos or the embryos of other mammals. We don’t know whether these developments will lead to safe and acceptable clinical human germline editing, especially if the gene-editing is restricted to human embryos. The technical, ethical, and regulatory challenges remain formidable. Maybe if the gene-editing process could be carried out from stable parent cell lines that could produce eggs and sperm in-vitro, there could be major breakthroughs in the future. As computers evolved from being a nerdy and a niche tool for doing math, to an omnipresent smart device, capable of easily performing everyday tasks, so will CRISPR transform itself into a technology beyond anyone’s imagination!
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