Author: Arthur Hu
Introduction
In our modern world, many issues have emerged regarding the production, distribution, and nutritional value of the food we eat, both in poorer countries that are at risk of starvation and in the USA, where pesticide overuse and resistance threaten crops. To find a solution to these problems and others, various groups have turned to genetic engineering and genetic modification. Genetic modification and genetic engineering are both forms of technology that can alter the traits of a living organism by changing its DNA, and while they are technically different from each other, their methods and results are similar enough that they can be sort of lumped into a single field, where advances in one will translate to similar progress in the other. For this reason, I will be covering them as a single topic in this article.
Principles/Mechanism
To understand genetic engineering, it is important to first understand what DNA is, and how changing it can affect the organism that results from it. Essentially, all living organisms are made out of tiny living parts made of cells, which you can think of as little sacks that work like robots, and DNA is the “code” that tells each cell what to do. In plants and animals, every living cell (with a few exceptions) has a nucleus that contains its DNA, and every cell within the same person has an identical copy of the same DNA (with a few exceptions). Cells can also divide into two identical cells in a process called mitosis, which gives each new cell a copy of the original’s DNA. Since every complex plant or animal starts as a single cell that then divides a lot of times, editing the DNA in that one cell is enough to change the sequence in every cell of the full-sized organism, as well as the sequences passed down to its children, grandchildren, and so on. In this way, genetic engineering can potentially cause massive changes to a population, and it is very hard to predict its long term effects. For example, if you engineered a gene (DNA sequence) for herbicide resistance into a field of corn, but a closely related weed species was able to reproduce with the modified corn, then while you may make it possible to indiscriminately spray your field for the next few years without killing your crops, in the long run, it could end up making your methods completely useless if the trait spreads into the weeds as well.
Methods
Tools for manipulating DNA (ligase and restriction enzymes) started appearing in the early 1970s, but genetic engineering only really became possible on a large scale once an artificial process for copying DNA (called PCR) was invented in 1983. Restriction enzymes are special chemicals with the ability to cut DNA wherever a certain sequence shows up in it, but could only cut at one spot each. In addition, because they are derived from bacteria, not every sequence can be cut by a restriction enzyme, so options for what segments you could cut out, and thus which genes you could transfer between organisms, were very limited. In contrast, DNA ligase can join any two DNA strands with ends that match, so as long as you could find a restriction enzyme that cut in a particular place, any segment that it removed could be “pasted” in. However, to actually use the DNA, you have to transfer it back into a living cell either through viruses, electricity, or a gun (no really).
Using these tools, you can edit the genome of an organism to remove, mutate, or even add genes from a different species to a limited extent. For relatively simple traits, like production of certain drugs, it is possible to make bacteria that do this in large numbers due to their rapid multiplication and harvest the drug from them, but for food products or other crops, more complex organisms must be modified instead. In any case, however, it’s important to make sure that essential genes are not disrupted enough to kill whatever organism you engineer, unless that’s the point of the engineering.
Applications
In the current day, genetic engineering is mostly used in the pharmaceutical and agricultural industries, although there are some other applications that are being explored. Medical applications include the production of insulin, human growth hormone, clotting factors, and other medicines that were previously only obtainable through organ harvesting, and cancer therapies that involve editing the DNA of the patient’s own blood cells to more effectively fight the disease. There is also ongoing work into creating “gene therapies” which edit the DNA of people affected with genetic diseases to cure them permanently, but so far, these are still mostly experimental. In medical research, genetic engineering has allowed for the creation of animal models with genetic diseases engineered into them, and by removing or adding genes, it also allows researchers to determine the function of certain genes.
In the agricultural sector, there have been many variants on pest or disease-resistant crops, with a notable example being the GMO papaya, which is probably the sole reason that papayas as a whole weren’t wiped out by the ring-spot papaya virus in the ’80s. On the other side of the coin, there have also been plants engineered to encourage the use of pesticides instead of limiting it, like the Roundup-Ready, pesticide-resistant soybean line. In addition, some efforts have been made to create versions of crops that are more nutritious or grow better in harsh conditions, but these have not become commercially viable yet.
Problems/Issues
While the applications of genetic engineering technology are diverse and powerful, its potential for misuse and safety concerns are just as common. For one, since the technology is relatively new, most governments don’t have a process for approving the use of genetically modified organisms, which has caused a whole host of complaints from various groups that applications are being approved that really shouldn’t be. In addition, copyright laws for the modifications made to a living organism’s genome also vary by country, which has led to companies suing farmers for using their modified seeds without permission, several cases of biopiracy, where rivals have stolen organisms from their competitors in the pharmaceutical industry, and the development of crops engineered to produce non-viable seeds, which force farmers to buy new ones every year instead of using their harvested crops for replanting.
The largest controversies so far have been over whether genetically modified crops are inherently more dangerous than unmodified crops, and whether or not they should be considered safe for human consumption. For example, in the vast majority of the countries in the EU, GM foods are outright banned, and in the rest, they have to be specifically labeled. While there haven’t been many studies that have found proof that they are inherently worse for people, some have argued that the farming practices they encourage are worse for the environment, and there are certain risks to growing these kinds of crops when compared to non-modified versions.
Recent Developments
Most currently available genetically modified or engineered products were made using the molecular biology techniques described earlier, which are limited in scope in terms of the large segments they can insert and how accurately they can create small changes in the genetic code. However, recently a new system called CRISPR has been developed that allows scientists to cut, copy, and paste any segment of the genome from anywhere, to anywhere. The mechanism behind this was derived from a bacterial anti-virus defense system, where using a saved copy of a virus genome and the protein CAS-9, some bacteria are able to cut dormant viruses out of their own genomes before they emerge. Not only is CRISPR more versatile, but it’s also cheaper, as one molecule can now handle all of the steps that multiple enzymes used to do separately, eliminating the need to order many expensive materials. This opens the door to a lot more experimentation, but because the technology is so new, there hasn’t been enough time for it to produce many results. One notable exception to this is the incredibly controversial birth of two human babies that had their genomes modified with CRISPR in late 2018, but for the most part, its potential is still largely unexplored.
Bibliography:
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Hoseini, S.S., Sauer, M.G. Molecular cloning using polymerase chain reaction, an educational guide for cellular engineering. J Biol Eng 9, 2 (2015). https://doi.org/10.1186/1754-1611-9-2
Khan S, Ullah MW, Siddique R, et al. Role of Recombinant DNA Technology to Improve Life. Int J Genomics. 2016;2016:2405954. doi:10.1155/2016/2405954
Author Biography: Arthur Hu is a junior at Lexington High School, Lexington, MA. As an attendant of the 2020 USABO Finals and the 2019 USESO camp, he has been heavily involved in the fields of biology and earth science. In addition, Arthur has also built up a background in other fields of science through his participation in various olympiads (USAPHO, USNCO) and competitions. In his free time, he enjoys reading and playing the violin.