Genetic Engineering and Bioethics: Changing the World Forever

The National Human Genome Research Institute defines genetic engineering as “the direct manipulation of one or more genes” (“Genetic Engineering”). Genetic engineering takes a gene pool that previously had been selected by nature, or in the religious view selected by God, and allows a human to manipulate it. As shown through classic literature such as Frankenstein, written by Mary Shelley, man playing God and messing with nature hardly ever ends well, however, with new technology is this about to change?  Since the first genetically engineered organism was created in 1973 (Rangel), the technology has evolved to be cheaper, quicker and easier to use (Ledford). With new technology, such as CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats), we are able to adjust individual genes in animal genomes to eliminate diseases, we have the potential to edit heritable traits, and the power to change the human population and other species for better or for worse, forever (Ledford). 

One of the most recent developments in genetic engineering is the CRISPR-Cas9 technology that allows us to edit genomes with RNA, however humans have been selecting favorable traits for some 30,000 years. According to Harvard Graduate School of Arts and Sciences, artificial selection is “the process of choosing the organisms with the most desired traits and mating them with the intention of combining and propagating these traits through their offspring”(Rangel). Around 32,000 years ago humans began domesticating dogs, this is one example of early genetic modification. It is thought that dogs evolved from wolves over time through artificial selection. Humans would select wolves with desired traits and keep breeding them. Over time these animals became less ferocious and came to resemble the dogs many have as pets today (Rangel). 

More recently, technology has evolved and modern genetic modification has become an important field. Starting in 1973 when two scientists, Herbert Boyer and Stanely Cohen successfully cut and pasted genes for antibiotic resistance in bacteria, the field has rapidly evolved. One year later Rudolf Jaenisch and Beatrice Mintz performed a similar experiment to introduce foreign DNA into mouse embryos, creating the first genetically engineered animal. This opened up the field of genetic engineering and many more experiments began taking place resulting in food and drugs produced through genetic modification. Due to the quick development of the technology, legislation was necessary. Some of the first legislation that was made was discussed at the Asilomar Conference on Recombinant DNA in 1975. During this time genetic engineering technology had just begun and there were many concerns. At Asilomar it was agreed that research should continue but under strict guidelines. It was determined that genetic modification would prove to be important in the development of new drugs and food varieties therefore experiments needed to continue (Berg). This conference allowed the public to gain trust in the scientists, allowed scientists to establish rules around contamination and risk reduction, and made sure that the labs were focused on safety. These regulations were subject to change as more information was gained in the field (Rangel). In 1980 a landmark Supreme court case changed the field of genetic modification. The court ruled that General Electric could patent a genetically modified bacteria that helped with oil spill mitigation. Two years later the US FDA approved Humulin, a drug produced by a genetically modified organism that synthesizes insulin allowing the production of insulin that can be sold to type 1 diabetics. In 1992 FLAVR SAVR tomatoes were the first genetically engineered food to be approved by the U.S. Department of Agriculture. After this there was no turning back. Since then the EPA has approved insecticide producing crops and herbicide-resistant crops. Finally, in 2009 the US FDA approved a drug, ATryn, to treat a rare blood clotting disorder produced by a genetically modified animal (Rangel). So where are we now?

Now new technology is developing, starting in 2012 a technique known as CRISPR-Cas9 spread through the biotechnology industry. With this technology, changing the DNA within any organism became more efficient, and instead of taking years it took weeks and could cost about $30 (Ledford). Discovered by Jennifer Doudna and Emmanuelle Charpentier CRISPR uses the Cas9 enzyme that can slice DNA. Used in bacteria to fight off viruses, it was found in 2012 that it can be used for animal genome modifications as well. Cas9 fights viruses in bacteria “by sending the Cas9 enzyme to chop up viruses that have a mug shot in the collection” (Saey). A mugshot refers to a small piece of a virus used for identification. In humans Cas9 can be used by starting with RNA that will give the enzyme instructions of what to cut and replace. The RNA will enter the nucleus where DNA is stored and find the segment it needs to edit. Cas9 will then latch on the double helix DNA and unzip it, allowing the RNA to pair with the desired DNA. Cas9 will snip the DNA and the cell sensing something is off will now repair it with the desired change. With CRISPR comes a whole new realm of possibilities in biology. 

With this technology comes many positive discoveries and uses, from vaccines to eliminating disease. There is no doubt this will change the world. The first FDA approved human drug made with genetic engineering was approved in 1982. This drug, humulin, is human insulin used for treating diabetes. Licensed to Eli Lilly it radically changed the field (National Museum of American History). Prior to its development insulin from cow and pig pancreases were being used, this new insulin was made by “inserting human genetic instructions into a bacterium that then produces the drug”(Altman). Humulin allows people with type 1 diabetes to manage their blood sugars. After this discovery it greatly changed how insulin was made and since it was the first genetically engineered drug approved for human use it opened up the field for many more discoveries. 

Another more recent medical discovery that uses genetic engineering is the Oxford AstraZeneca COVID-19 vaccine. This vaccine, made with adenovirus, uses the spike protein of the corona virus to generate an immune response. The vaccine uses the genetic material that codes for the spike protein and stores it as DNA in a modified chimpanzee adenovirus, a virus that causes cold symptoms in humans. This genetically altered virus can get inside cells but cannot reproduce therefore it is harmless. Once in the body the adenovirus will be pulled into the cell where it will release the modified DNA with the coronavirus spike protein DNA into the nucleus. The DNA holds instructions that code for a spike protein. These spike proteins will be made in the cell and displayed on the outside causing B-cells to begin making antibodies. These antibodies will allow your body to fight covid should it be detected in your immune system (Corum and Zimmer). Genetically engineered vaccines like AstraZeneca have been key to ending the pandemic. As we begin to see restrictions lifted in some countries and life returning to normal we are seeing the positive effects of genetic engineering. We can predict that without this technology many thousands more lives would have been lost to this deadly virus. 

While not fully developed, genetic engineering shows promise against defeating HIV (human immunodeficiency virus). In 2015 Scientists were able to cut HIV out of living cells in a lab, a year later they were able to use CRISPR-Cas9 technology in an experiment with HIV infected rats. These rats had the HIV virus in nearly all of their cells, the rats were then injected in their tails with CRISPR designed to target the virus. Simply by doing this scientists were able to remove more that 50% of the virus cells from the body (“Genetic Engineering Will Change Everything Forever – CRISPR”). While this may be further down the road and still needs some testing, if replicated in humans HIV/AIDS (acquired immunodeficiency syndrome) could be a deadly illness of the past. More recently this experiment has been done in rhesus macaque monkeys infected with SIV(simian immunodeficiency virus ), a frequently used model for HIV. About this experiment Kamel Khalili, Ph.D., of the Lewis Katz School of Medicine at Temple University in Philadelphia said “We show for the first time that a single inoculation of our CRISPR gene-editing construct,carried by an adeno-associated virus, can edit out the SIV genome from infected cells in rhesus macaque monkeys”(Kaltwasser). While this technology shows promise in small mammals this doesn’t guarantee that it will work in humans and there are some ethical issues that must be worked out. 

With genetic engineering comes the complex topic of bioethics. According to Michigan State University, Bioethics are commonly understood to be “the ethical implications and applications of the health-related life sciences” (“What is bioethics?”). Bioethics has been a discussion for a long time. As shown in Mary Shelley’s Frankenstein, Victor, the main character, creates a modified organism without considering the consequences. In present day genetic modification it is important to consider the effects prior to using it. Since 1973 when the first organism was genetically engineered there have been many ethical questions: What effects will genetic engineered animals have on ecosystems? What effects will genetically modified humans have on the genepool? And lastly, is genetic engineering ethical?

 Seeing as CRISPR technology is rather new and still comes with challenges and unknowns, scientists are hesitant to use it on animals. For example, recent experiments with CRISPR to protect mosquitoes from carrying the malaria virus have unknown consequences. Scientists do not know what will happen when they are released into the wild. The hope is that the genetically modified mosquitoes will reproduce and help eliminate the parasite (University of California). What scientists don’t know is what effect they will have on the food chain and on ecosystems. Seeing as genes will naturally mutate over time, what will happen down the road raises the question: is it really man’s job to manipulate natural selection? These genes that we are changing in a mosquito have the potential to mutate into something more dangerous down the road. Who is responsible for monitoring these effects and dealing with them if it all falls apart? Having malaria resistant mosquitoes is beneficial mainly to humans not the mosquitos or their ecosystem, so is it something that needs to happen? While malaria is a threat, if it naturally hasn’t gone away it could be here for a reason. If humans start playing God, we can’t undo what we have done. 

Another issue that comes into play is: What effect will genetically modified humans have on the genepool? For example in 2018 He Jiankui, a Chinese scientist, announced the birth of genetically modified twins. Their embryos had been edited with CRISPR to be immune to HIV. This unpredicted announcement led to severe concerns (De Nardi Sanches-da-Silva, Gabriela, et. al.). He had created unseen genetic edits that will have a lasting impact on humans. Jiankui violated bioethics principles, international consensus guidelines, and national regulations. The International Journal of Genomics says “The Committee for the International Summit on Human Gene Editing established, among other issues, the need for intensive basic and preclinical studies in accordance with ethical principles and that ‘modified cells should not be used to establish a pregnancy’” because of this it was determined that Jiankui would be jailed for 3 years and fined (“China jails ‘gene-edited babies’ scientist for three years”). An additional complication is that genetics are a big part due to chance, however with technology like CRISPR humans can pre-select for favorable traits creating so-called perfect organisms. This becomes eugenics. Looking at humans, everyone is different. If CRISPR becomes readily available to edit out deadly diseases in our genes, why not add a faster metabolism, or blue eyes and blonde hair, whatever is considered to be perfect? As the technology evolves it may be considered unethical not to use it because you would allow your offspring to live with suffering that could have been prevented (“Genetic Engineering Will Change Everything Forever – CRISPR”). This will forever change the gene frequencies and is a huge power. Eugenics in the past has been used by oppressive governments such as the Nazi regime. With technology like this it is incredibly important that we are only using it when it is necessary. So is it ethical? Each person will have their own opinion, personally I believe it is ethical to an extent. In my opinion, using CRISPR to edit out deadly diseases in the human genome is ethical, however we must be cautious with its uses. I believe that there needs to be strict oversight on experiments to prevent misuse. While genetic engineering technology has massive payoffs it is important that we don’t discount the potential negative effects. 

Genetic modification technology has been evolving for many years. From selective breeding to gene modification, humans have been changing different species for a long time. As genetic engineering technology has evolved so have the ethical concerns associated with it. While the benefits are numerous it is important not to discount the irreversible consequences. We must think about how we will handle the effects prior to using the technology and interfering with nature. Classic literature has been grappling with the effects of humans playing God for quite some time, as shown in Frankenstein. In the novel, when Victor creates the Wretch he does not consider the consequences, and there are severe repercussions. In Victors case it was murder, however with genetic engineering that may not be the case but we will still be radicaly changing the world. As science pushes forward we must ask ourselves: are we ready to deal with the consequences of this type of genetic manipulation?

 

Works Cited 

Altman, Lawrence K. “A New Insulin Given Approval for Use in U.S.” The New York Times, 30 Oct. 1982, https://www.nytimes.com/1982/10/30/us/a-new-insulin-given-approval-for-use-in-us.html#:~:text=The%20new%20insulin%2C%20called%20Humulin,that%20then%20produces%20the%20drug. Accessed 23 May 2021.

Berg, Paul. “Asilomar 1975: DNA modification secured.” Nature, 17 Sept. 2008, https://doi.org/10.1038/455290a. Accessed 23 May 2021. 

“China jails ‘gene-edited babies’ scientist for three years.” BBC, 30 Dec. 2019, www.bbc.com/news/world-asia-china-50944461. Accessed 24 May 2021.

Corum, Jonathan, and Zimmer, Carl. “How the Oxford-AstraZeneca Vaccine Works.” The New York Times, 7 May 2021, https://www.nytimes.com/interactive/2020/health/oxford-astrazeneca-covid-19-vaccine.html. Accessed 23 May 2021.

De Nardi Sanches-da-Silva, Gabriela, et. al. “The Potential Use of the CRISPR-Cas System for HIV-1 Gene Therapy.” International Journal of Genomics, 21 Aug. 2019, www.hindawi.com/journals/ijg/2019/8458263/. Accessed 24 May 2021.

“Genetic Engineering.” Genome.gov, National Human Genome Research Institute, www.genome.gov/genetics-glossary/Genetic-Engineering#:~:text=Genetic%20engineering%20is%20the%20process,selecting%20offspring%20with%20desired%20traits. Accessed 23 May 2021. 

“Genetic Engineering Will Change Everything Forever – CRISPR.” YouTube, uploaded by Kurzgesagt – In a Nutshell, 10 Aug. 2016,www.youtube.com/watch?v=jAhjPd4uNFY. Accessed 24 May 2021.

Kaltwasser, Jared. “CRISPR Gene-Editing Shows Promise Against HIV.” Managed Healthcare Executive, 4 Jan. 2021, www.managedhealthcareexecutive.com/view/crispr-gene-editing-shows-promise-against-hiv. Accessed 24 May 2021.

Ledford, Heidi. “CRISPR, The Disruptor.” Nature, 03 June 2015, https://www.nature.com/news/crispr-the-disruptor-1.17673#/rise. Accessed 23 May 2021. 

National Museum of American History. “Humulin N, NPH, human insulin (recombinant DNA origin) isophane suspension.” https://americanhistory.si.edu/collections/search/object/nmah_1000967. Accessed 23 May 2021.

Panuwach. “Gene editing tool research illustration.” Shutterstock, www.shutterstock.com/image-vector/crispr-cas9-genetic-engineering-gene-editing-1315440554.Accessed 26 May 2021. 

Rangel, Gabriel. “From Corgis to Corn: A Brief Look at the Long History of GMO Technology.” Harvard University, 9 Aug. 2015, sitn.hms.harvard.edu/flash/2015/from-corgis-to-corn-a-brief-look-at-the-long-history-of-gmo-technology/. Accessed 23 May 2021. 

Saey, Tina Hesman. “Explainer: How CRISPR Works.” Science News for Students, 31 July 2017, https://www.sciencenewsforstudents.org/article/explainer-how-crispr-works. Accessed 23 May 2021.

University of California – Irvine. “Researchers pioneer more effective way to block malaria transmission in mosquitoes: New CRISPR-based gene drive approach successfully overcomes issue of resistance in females.” ScienceDaily, 3 Nov. 2020. www.sciencedaily.com/releases/2020/11/201103140613.htm. Accessed 23 May 2021.

“What is bioethics?” Michigan State University, https://bioethics.msu.edu/what-is-bioethics. Accessed 23 May 2021.