An introduction to the multiple-award-winning tool within the fields of biotechnology
Note: words formatted in bold are ones which can be found in the glossary.
Genetic engineering, a word often flashed by the media as ultra-modern and on the forefront of breaking edge research, in fact has very humble origins, dating as far back as 10,000 years ago. Genetic engineering pertains to the control and manipulation of the expression of different genes in an organism, so that a more preferable or more desired characteristic may be predominantly expressed. Since the dawn of farming practices, there has always been an interest in maximising crop yield, protecting crops from harsh weather and rearing the most perfect cattle to maximise profits. Farmers, to an extent, in fact achieved these goals, albeit in a way that does not, per se, denote the intrinsically scientific and laboratory based approach that we in the 21st century are familiar with. By simply choosing the best of their crop, and the best of their cattle to favour and focus their efforts on, farmers have cast a bottleneck upon the expression and inheritance of characteristics, such that only those with the preferable ones may rise and proliferate. It is refreshing to note that it was not academics or scientists in labs that stepped on the path to genetic engineering, but rather, it began with simple farmers in their muddy fields.
Genes are sequences of DNA that code for the characteristics that each and every living organism possesses. Whether that is your height or the colour of leaves on trees, the parameters of these things are all controlled and expressed according to your genetic code. In modern times, man has traversed across vast fields of experimentation and analysis to more directly meddle with the genome. Most often, a gene from another species is added to an organism’s genome to give it a desired phenotype, creating what is known as the transgenic organism. The journey may have begun thousands of years ago, but it wasn’t until 1973 when the first sample of recombinant DNA was produced.
In 1973, American biochemists Stanley N. Cohen and Herbert W. Boyer became the pioneers of genetic engineering by recombination. This was the process of cutting parts of DNA into different fragments, joining different fragments together, and then inserting these into the genetic sequence of another organism. This first instance of recombination was achieved using restriction enzymes and the recombinant genes were inserted into the bacterium E.coli.
In modern biotechnology, the word genetic engineering is used to describe the insertion of a sample of foreign DNA into an organism. This foreign DNA could be from the same organism, or even from a different organism completely. Thanks to the fact that replication processes and enzymes involved are almost identical, along with the fact that the genetic code is degenerate, it is possible to exchange genes within different species to extract the purest blend of desired characteristics.
The first stage in making a GM (genetically modified) organism requires the removal of the target DNA using restriction endonucleases. These are enzymes that “chop up” the DNA at specific recognition sites, where palindromic sequences are found (antiparallel base pairs). When there are palindromic sequences around the target gene, the restriction endonuclease can cut out the DNA sequence so that the target gene is separated from the rest of the DNA strand. Certain types of restriction endonucleases are particularly useful because they leave small regions of DNA sticking out at each end of the required gene- these are unpaired bases. These are known as sticky ends, and make it much easier to attach the gene into another piece of DNA.
The second stage of the process is to produce something which can carry the DNA into the target host cell. A plasmid derived from a bacterium is often used as a vector. These replicate relatively quickly, hence they can amplify the gene in large amounts. The same restriction endonuclease that was used to cut the DNA fragment is used to cut the vector, leaving complementary sticky ends.The plasmid is able to join (anneal) with the target DNA, using enzymes also known as DNA ligase. A marker gene, incorporated into the vector DNA (the modified plasmid) is used to check which cells have managed to take up the plasmid containing the target gene, and can be used to identify and separate these from the cells that were unsuccessful in getting transformed. -General method by which recombinant DNA is formed.
The final step is to incorporate the recombinant DNA into the target host cell where it is required. This is usually achieved by heat shocking the bacteria, which causes their cell membranes to become more permeable so the plasmids can be taken into the cells. Once the plasmids are inside the host bacterium, the genes within it will be expressed and the required protein will be coded for.
There are a variety of examples where genetically modified organisms are being used for the benefit of mankind. Infact, it is playing a big role in our current situation too. The Pfizer and Moderna COVID-19 vaccinations, which millions of people have already taken in the past 6 months, actually uses the results of genetic engineering to build immunity against the SARS-coV-2 virus. mRNA, delivered to body’s cells by lipid nanoparticles, instructs the cells to generate the spike protein, found on the surface of the SARS-coV-2 virus, that is responsible for the initiation of infection2. Instructing cells to generate the spike protein initiates an immune response, including generation of antibodies specific to the SARS-CoV-2 spike protein. These mRNA vaccines don’t contain actual SARS-coV-2 virus particles which makes it more appealing to many as it validates their safety, though of course, other problems may arise.
Strangely, although somewhat appealing too, there’s been genetically modified bananas that act as vaccinations against diseases such as cholera and hepatitis. These GM bananas are delivered to third world countries, where these diseases are so common due to the living conditions and impurities present within drinking water. This method was developed back in the 1990s by biotechnologists at the Boyce Thompson Institute for Plant Research. These banana vaccines are ideal for third world countries as they only cost a pound in comparison to actual vaccinations, which would cost a lot more. In 1995, the team showed that hepatitis B antigens produced by genetically engineered potatoes triggered an immune response in rats. But because potatoes are not eaten raw, and cooking them would destroy the vaccine, they are unsuitable for vaccinating people. So the researchers switched their efforts to bananas, which are already grown extensively throughout the developing world4.
Genetic modifications have many long-lasting benefits, from increasing the yield of different crops, to spreading resistance against many life-threatening diseases among poorer communities, such as in third world countries.
But genetically modified plants and drugs aren’t just therapeutics that help to treat and prevent diseases. The future of genetic engineering holds a wide range of products for other fields of science too. Let’s consider human embryos: biophysics researcher He Jiankui had announced the first ever birth of twin girls, Lulu and Nana, with edited genomes. The news had astonished the world, even though his acts were identified as being “dangerous, unethical and premature” by the Chinese government, and had spread a lot of criticism and controversy. He had apparently conducted this process through human germ-line therapy, where he modified the gametes of a person causing heritable changes to every cell of the offspring 5. Of course, this is not yet something widespread, neither is it fully supported by the scientific community due to the dangers it poses. But this raised a lot of questions with regards to the process to biotechnology researchers, and there are many reports of research proposals which could be conducted to see really how successful it can be.
There is a lot of anticipation with genetic engineering for therapeutic drugs and cures to diseases, and other branches of medicine. But is it really something that will be so successful? Jamie Metzyl, author of “Hacking Darwin”, states that genetic engineering is allowing us to combat the second pillar of Darwanian evolution: random mutations. He describes how these genetic technologies, when making cures for cancers and many other diseases, are merely a “station” of what it has to offer us in the future. However, as everything, genetic engineering comes with several drawbacks.The very nature of altering an organism’s genome for our personal gain is an ethical issue contested by many. There’s skepticism surrounding the uses of GM crops and links with cancer have been speculated6. The main drawback with genetic engineering is it’s ambiguity and our lack of understanding. After all, the molecular structure of DNA was only discovered in 1952. In addition to this, it is vital these gene technologies are regulated or the after effects can be fatal on a large scale. This job is more difficult as technology is racing forward faster than the governance structures around them can keep up. It is extremely important that on a national and international level, strict regulations are kept so individuals do not misuse the technology and public safety remains highly promoted.
Genetic engineering is a cutting-edge, astonishing branch of biotechnology. It has provided many benefits for the clinical industry in the form of new treatments using genetic engineering. The fact that it uses DNA is what makes it so promising, as it gives scientists the ability to alter absolutely anything that makes up the human genome.
However, DNA was not discovered that long ago, so we don’t fully know the extent to which we can safely modify it, and the long term impact of modifying DNA is also unknown. For now however, there remains very little doubt in the ability of genetic engineering to benefit us humans. Just as it improved the life of the farmer pioneers and those around them many thousands of years ago, so it possesses the ability to benefit us. It is interesting to note though, that regardless of what we may now discover in this journey further and deeper through cutting edge science, it remains a double edged sword. Just as we may gain much from it, it must be controlled and chained to the virtues of moral conduct and ethics, else we may tread too far from the path of humanity, and stray onto the path to a dystopian and cruel future.
|Foreign||Something which the organism isn’t used to, causing the immune system to form an attack against it.|
|Plasmid||Circular DNA, alongside main chromosomal DNA, containing genes that code for characteristics such as antibiotic resistance in bacteria.|
|Vector||Something used to transfer modified DNA to a host cell.|
|Amplify||Increase the frequency of the gene.|
|SARS coV-2 virus||Virus that causes COVID-19|
|Lipid nanoparticles||Solid lipid nanoparticles, or lipid nanoparticles, are nanoparticles composed of lipids. They are a pharmaceutical drug delivery system|
|Genome||All of the genetic material that an organism has:the complete set of genetic instructions.|
|Mutation||An alteration to the base sequence of DNA|
|CAR-T Therapy||A type of immunotherapy which involves collecting and modifying the patients’ own immune cells to treat their condition.|