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There was a short time after the discovery of the structure of DNA by Watson and Crick in 1953 where people were excited at its potential in changing lives - but had no way of changing DNA. It seemed immutable, only to be observed and studied and never to be touched. The budding new field of molecular genetics seemed to be stuck. It was a whole 20 years later, in 1973, that Boyer and Cohen first created genetic engineering, where DNA from one bacteria was inserted into another (FDA, 2024). They were inspired by the transfer of genes between bacteria, what we now call horizontal gene transfer. This has led to GMO crops and gene editing. There is much discussion about the ethics and safety of all these innovations. To truly understand what is going on, is it important to understand the Biology behind genetic engineering.
Gene transfer
All of our genetic information is in our chromosomes. Genes are specific parts of a chromosome that codes for a specific product - such as a protein, or an RNA - that can move through the cell or organism to exert its effect.
Typically, our genes are from our parents. When mummy and daddy love each other very much… the egg and sperm combine to eventually form us. This is also the case for animals, plants, fungi, as well as smaller organisms like bacteria (although unlike us they only have one parent). This is termed vertical gene transfer - genes go DOWN the family tree.
However, there exists a phenomenon called horizontal gene transfer (HGT). Imagine you can package up your DNA and give it to your friend… Faith. This is precisely what happens between cells. There are 4 processes, conjugation, transformation, transduction, and vesiduction (Soler and Forterre, 2020), that allow HGT to occur.
Conjugation: contact leads to formation of conjugation tube
Transformation: uptake of DNA from environment
Transduction: bacteriophages (bacteria viruses) infect one bacteria and transfers DNA to another bacteria
Vesiduction: transfer via extracellular vesicles
I would like to highlight that this process mostly occurs and is most well-known in bacteria. However it can also happen in eukaryotes (the group including plants and animals), and more of such cases are being found in recent years.
Genetic Engineering
This natural process has been utilised for genetic engineering, which is the manipulation of genes to get what we want. The first method developed was recombinant technology, which involves the insertion of a gene of interest into a cell to create a recombinant/transgenic cell (note that these terms have slightly different meanings, transgenic is more general which recombinant refers to this specific technique). It utilises transformation - although it was inspired by transduction (and gene transfer in general).
Transformation involves the uptake of DNA from the environment. In order for the specific gene we want (gene of interest) to enter bacteria, we need to use a vector, and insert the gene of interest into the vector. A commonly used vector is a plasmid, a small circular DNA found in bacteria, archaea, yeast and many others. Then, we shock the bacteria, allowing small holes to form in the bacteria cell wall and transformation to occur. Those cells - called transgenic cells- can then express the gene of interest.
The first big innovation using this technique was insulin producing bacteria. Prior to that, insulin was produced from pig pancreas - which could cause allergies, and was more expensive (American Diabetes Association, 2019). This method allowed for mass production of insulin, which keeps 200 million people alive every year (Buse et al., 2021).*
Then, we set our sights on bigger targets: plants. A species of bacteria called Agrobacterium tumefaciens** can infect plants. In agrobacterium, there are specific plasmids called Ti plasmids, which contain T-DNA. Upon infecting a plant, T-DNA is integrated into the plant’s genome (the term for all of an organism’s genetic information). This is one way bacteria use to infect plants, but its ability to harm the plant is stopped by the insertion of the gene of interest into the T-DNA.
This is the process used to create various GMO crops, such as pest-resistant Bt corn, flood tolerant scuba rice, provitamin-A rich golden rice, and many others. This helps plants grow and thrive despite the changing climate, and increase nutritional content, increasing reliable access to food for you and me.
Gene engineering is also a key part of cell gene therapy, and has been used to treat many genetic diseases like sickle-cell anaemia and cystic fibrosis. With the increase in methods for gene editing, such as by using different vectors, or by other techniques like CRISPR, RNAi, trans-splicing, there has been more progress in treating a variety of human diseases, and even the talk of editing germline cells that eventually form a person’s child (this is not currently allowed).
Progress will continue to occur in gene engineering. It is an inevitable future. We, as a society, need to decide what kinds of gene engineering and editing we are okay with, and which to restrict.
*According to WHO (2024), less than 50% of those who need insulin have access to it, due to various factors such as pricing and availability.
**Also known as: Rhizobium Radiobacter. A lot of organisms (and bacteria in particular) get reclassified and then renamed, due to changes (and disagreements) about taxonomy.
Reference List
FDA (2024). Science and History of GMOs and Other Food Modification Processes. U.S. Food and Drug Administration, [online] 1(1). Available at: https://www.fda.gov/food/agricultural-biotechnology/science-and-history-gmos-and-other-food-modification-processes.
Soler, N. and Forterre, P. (2020). Vesiduction: the fourth way of HGT. Environmental Microbiology, 22(7), pp.2457–2460. doi:https://doi.org/10.1111/1462-2920.15056.
Liu, Y., Tong, Z., Shi, J., Jia, Y., Yang, K. and Wang, Z. (2020). Correlation between Exogenous Compounds and the Horizontal Transfer of Plasmid-Borne Antibiotic Resistance Genes. Microorganisms, 8(8), p.1211. doi:https://doi.org/10.3390/microorganisms8081211.
American Diabetes Association (2019). The History of a Wonderful Thing We Call Insulin. [online] diabetes.org. Available at: https://diabetes.org/blog/history-wonderful-thing-we-call-insulin.
Buse, J.B., Davies, M.J., Frier, B.M. and Philis-Tsimikas, A. (2021). 100 years on: the impact of the discovery of insulin on clinical outcomes. BMJ Open Diabetes Research and Care, [online] 9(1), p.e002373. doi:https://doi.org/10.1136/bmjdrc-2021-002373.
Hawkins, E. (2017). What is plant transformation? | John Innes Centre. [online] John Innes Centre. Available at: https://www.jic.ac.uk/blog/what-is-plant-transformation/.
WHO (2024). Diabetes. [online] World Health Organization. Available at: https://www.who.int/health-topics/diabetes#tab=tab_1.
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