Genetic engineering has been a staple of the news and science fiction alike since the 1970s when techniques for editing DNA sequences were first developed. In this week's article, I hope to separate the fact from the fiction and provide you with an overview of how genetic engineering works and its uses in the modern world. I will also highlight the ethical concerns associated with its use.
The story of genetic engineering begins in 1972 when the first artificial modification of genes was carried out by Herbert Boyer and Stanley Cohen. Boyer and Cohen were able to carry out the process of transgenesis, where genes from one organism are artificially transferred to another, changing its genome. As such, their work was crucial in the development of recombinant-DNA technology (technology still used today which, according to the Science History Institute, is the way in which 'genetic material from one organism is artificially introduced into the genome of another organism and the replicated and expressed by that other organism').
The science behind recombinant-DNA (shortened to rRNA but not to be confused with ribosomal RNA) provides the backbone of how we carry out genetic engineering. rRNA molecules are DNA molecules that consist of DNA from two or more organisms, creating sequences of genes not normally found in the organism. As such, the production of these molecules can be very beneficial for medicine, science and industry.
CRISPR (short for CRISPR-Cas9) is a cutting-edge technique, developed in the last few years, that allows scientists to edit the genome of an organism. CRISPRs, which stands for 'clusters of regularly interspaced short palindromic repeats', are sequences of 30 nucleotide pairs which have palindromic sequences and are found in clustered regions of DNA. In each region, the palindromic bases are interspaced with other pieces of DNA called spacers. In bacteria, these spacers are similar to the DNA sequence of bacteriophages (viruses that infect the bacteria) which have previously attacked the bacterium. As such, this helps the bacteria recognise bacteriophages and fight off future attacks. However, these spacers can also be used in genetic engineering.
When the bacterium is exposed to a foreign genome (which happens when a virus attacks it), the spacers are synthesised producing CRISPR RNA (crRNA). With the assistance of trans-activating crRNA (tracrRNA), the crRNA is able to guide a nuclease enzyme (an enzyme that cuts DNA chains into shorter sequences) to the foreign genome and cut out a piece of its DNA, rendering it inactive. Once a sequence of DNA is removed, the DNA then repairs itself. If it does not, then a DNA patch is provided artificially to bridge the gap in the sequence. Since 2012, we have been able to replace these spacer elements with other DNA sequences and keep the CRISPR mechanism for genetic engineering working in other species, thus allowing us to use the CRISPR mechanism for cutting out genes from the DNA of many other species including humans.
CRISPR technology has many medical applications which could help people with genetic diseases, such as cystic fibrosis and diabetes. This is because mutant alleles could be removed from an affected human's genome, or even replaced with a copy of the unaffected DNA sequence. Caution must be taken however as a study published in June 2018 discovered that editing cells' genomes using the CRISPR mechanism increases the risk of cancer.
The use of CRISPR technology in medicine is not limited to genetic diseases but can also help with organ transplantation, specifically with the use of organs harvested from pigs. Currently the world has a massive shortage of organs for use in transplant, with 6209 people waiting for organ transplants in the UK as I write this article. As such, scientists are turning to pigs to act as donors to save human lives. Leaving aside possible ethical considerations with this idea, the main problem with using organs harvested from pigs is that pigs have retroviruses presence in their genome. When viruses have infected pigs, they have inserted some of their genes into the pig's DNA, which is then passed on to their offspring. As such, over multiple generations, the pig's genome is full of dormant viruses which may get activated after transplantation and cause disease in the human. Nevertheless, by using CRISPR technology, Harvard researchers were able to remove 62 of these retroviral sequences from the pig genome, reducing the risk of future viral diseases after transplantation.
Despite the benefits that genetic engineering, there are many ethical concerns about it, especially when it comes to experimenting on embryos. One of the most pressing concerns about this is that some people believe that an embryo has the same rights as an adult human and, as such, any procedure performed on an embryo must pass the same ethical considerations as if it were performed on an adult. Considering that the vast majority of these experiments would not pass this benchmark, a significant number of people believe that genetic engineering trials should not be carried out on embryos.
Moreover, there is also concern that the genetic engineering of humans could be used for creating "designer babies", where the genome of the baby is edited for improvement instead of medical need. One problem of many that this creates is to do with the field of sport, as athletes could be able to enhance their bodies, giving them an unfair advantage over other competitors.
In November 2018, a Chinese scientist announced that he had created the world's first genetically edited babies, sparking ethical condemnation across the globe, despite the advances in science that it represented. Professor He Jiankui of the Southern University of Science and Technology in Shenzhen announced that he had changed the DNA sequence of the two twin girls, preventing them from contracting HIV and that he had altered embryos for another six couples as well.
All seven couples consisted of an HIV-positive father and HIV-negative mother, making it likely that the babies of each couple would also have HIV. However, He Jiankui used CRISPR technology to knock out the CCR5 gene that allows the HIV virus to attack the immune system, thus making the babies resistant to HIV.
This work, once announced in 2018, was immediately condemned by the scientific community and Chinese government, due to the ethical and legal violations that he had committed. Not only did he commit a crime in China by forging ethical review documents and tricking doctors into implanting the genetically modified babies into two women's womb, which resulted in him getting a 3-year prison sentence, but his procedure also brought no benefit for the babies, as he was simply solving a problem of his own creating. Furthermore, there are many other ways of preventing HIV transmission which doen't involve genetic modification. In addition, there are also some concerns that these babies may be at greater risk of contracting other diseases.
Moreover, genetic engineering is also used in agriculture, mostly to help plants and animals resist disease. This is because most pathogens work by interacting with proteins expressed by the host. By removing the genes responsible for the expression of these proteins using CRISPR technology, we can prevent the pathogens from causing disease in the plants and animals. Nevertheless, this has several ethical concerns, not least of which that this technology enables farmers to keep animals in worse living conditions as, since they are immune from many diseases, their conditions do not have to be as hygienic.
Genetic engineering can also be used to produce genetically modified crops which can have more nutritional qualities or be able to grow in tougher conditions. An example of this is golden rice, which is modified to have increased amounts of vitamin A, thus helping prevent irreversible childhood blindness. Generally, the scientific community agrees that GM crops are very beneficial in terms of the support they give to the human population, especially to regions where farming is essential for economic prosperity. Nevertheless, due to concerns regarding their safety, they have been banned in the EU.
In conclusion, I would suggest that we must be careful when developing CRISPR techniques in both humans and animals as, not only does genetic engineering bring with it the increased risk of cancer, but there are also numerous ethical concerns with its use. Furthermore, all new techniques must be constantly approved and monitored by ethics boards to ensure that they meet strict ethical guidelines.
Thank you for reading this week's article. If you enjoyed it, I suggest you read my article on three-parent babies (https://hippocratesweekly.wixsite.com/blog/post/three-parent-babies) and subscribe to my mailing list so that you get notified about future articles.
Sources:
Biological Sciences Review Magazine, September 2019: Genome editing
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