Difference between revisions of "Embryonic Genomic Engineering"

Revision as of 18:55, 26 January 2023

Genomic editing is a hot topic in precision medicine today. Through the use of technology, individuals in the healthcare field are able to modify live genomes. Many of these genomes are modified during the embryonic stage of development, also known as gametic editing. With the discovery of CRISPR-cas9, genome editing possibilities began to take off. CRISPR-cas9 is a system in the human body's immune response that “cuts” the DNA of invasive pathogens to protect bodily cells from harm. A group of researchers discovered in 2012 that this tool could be used to target specific sequences in the human genome in order to alter its structure and, ultimately, function ^[1]. CRISPR has been at the forefront of gene editing since its discovery, but other methods have also been developed. With more research being conducted on this topic, the possibilities with this new technology are becoming clear. It is possible to modify genomes in order to slow disease progression, cure diseases, and even change an individual's phenotypic characteristics. This technology has numerous applications, ranging from curing diseases like HIV to allowing parents to select certain characteristics for their offspring. The window of applications has only just begun for this biotechnological process and has the potential to progress significantly in the near future.

As this technology advances, bioethical concerns become a topic of discussion. How far can new genomic engineering technology be taken? Is it acceptable to allow parents to select characteristics for their children? Is it permissible, on the other hand, to edit genomes in order to make an individual resistant to a disease? Given that some of these editing processes occur during the embryonic stage of a fetus, is it acceptable to carry out these procedures in the absence of consent from the individual being edited? All of these questions, along with many others, are of debate in the field of genomic editing. This page discusses the methods, technology, and ethical implications of genomic engineering, particularly with regard to embryonic or germline editing.

History

Many advances have occurred over the years, bringing us to where we are today in the field of genomic editing. There are several genome editing technologies available, including ZFNs, TALENs, and CRISPR-cas9 ^[2]. CRISPR-cas9 has been at the forefront of genetic engineering since its discovery due to its higher precision rates and self efficiency when compared to other methods. CRISPR principles were discovered by researcher Francisco Mojica in 1993. In the discovery of this locus, “this finding led him to hypothesize, correctly, that CRISPR is an adaptive immune system” laying the groundwork for today's genomic editing technologies ^[3]. Following this, by the 2000s the necessary technology had been developed and the human genome was sequenced allowing for gene editing technologies to be researched more efficiently. Around 2012 to 2013, researchers such as Virginijus Siksnys and Feng Zhang discovered that CRISPR-cas9 could be used as a genetic engineering tool to target specific genes in the human genome ^[4]. CRISPR-Cas9 is now being used in embryonic gene editing and in clinical settings for targeted therapies. The field of genomic editing is still in its early stages, but with the advancement of healthcare and computational technologies, it will inevitably take off.

Somatic Gene Editing

Non-reproductive cells in the body are changed by somatic editing. This method only targets a specific gene in a single cell type. Changing this gene has no effect on other cells in the individuals' bodies. After somatic editing, the edited gene will remain within this individual and will not affect the genes of their future children.^[5][6]

Germline Gene Editing

Germline editing is done on "early-stage embryos, gametes (eggs and sperm), or germ cells that are the precursors of gametes" ^[7]. As a result of this, every cell in the embryo contains a copy of the edited gene. After this editing has occurred, there is the potential that the edited gene will be passed down to future generations. This is due to the fact that every copy in the embryo contains the edited gene, even sperm and egg cells. ^[8]

Germline genome editing processes are becoming more accessible in clinical settings than they were previously. Somatic genetic editing has already been approved in a number of clinical settings, making human trials with targeted therapies possible. This is because the editing is more controlled and the effects are restricted to the individuals being edited. Germline editing, on the other hand, has more unknown effects, increased factors, and more unethical implications. Since every cell in the individual has this edited mutation, it is difficult to determine what other unintended effects this induced change may have had. Currently, “any clinical trial proposals for germline alterations will be rejected by the Recombinant DNA Advisory Committee (RAC) of the NIH” ^[9]. Opposition to these laws is punishable by a fine, imprisonment, or both. In 2019, Jiankui He, a Chinese researcher, went against these guidelines to perform germline genomic experimentation. Jiankui used CRISPR technology to cause embryonic genetic changes that removed HIV-causing genes. His experiment was successful, but the ethical implications of using genomic editing technologies to interfere with human reproduction were controversial as “going against rules and doing such research is forbidden by the international biomedical community” ^[10]. Although unethical, the results of this experiment revealed significant implications for the impacts of germline editing in a clinical setting.

Ethical Implications

One ethical concern with germline genome editing is the potential consequences of inducing an edit without knowing the full extent of the effects. By doing so while being unaware of the consequences, the individual may end up with other complications later in life or complications in future generations of children. With the technology and knowledge available today, scientists are unable to comprehend the scope of all the unknown side effects of germline genome editing. This lack of understanding can cause modifications that were not intended to happen. One approach is to weigh the consequences of performing the editing procedure versus not performing it. Essentially, the question is whether the benefits of genetic engineering outweigh the risks and uncertainties of "exposing a child to the risks and uncertainties" ^[11]. Nuclear genome transfers are an example of where the benefits outweigh the risks. This eliminates mitochondrial mutations inherited from the maternal parent. If this is not done and the mutation is inherited, the individual is at risk of suffering life-threatening consequences ^[12]. This criterion is a major consideration in germline editing research. When do the advantages outweigh the disadvantages?

Another ethical concern is that these trials would be performed on embryos with the potential to develop into human beings. The question here becomes determining the embryo's moral standing. Do we regard the embryo in the same way that we regard a human being? Or do we regard them as merely a collection of cells? If we are to consider them as a human being, then conducting experiments in which we alter the genome while ignoring the consequences would be considered unethical. In contrast, if we consider them to be cells, then it should be theoretically equivalent to experimenting on any human tissue cell, which is done all the time. At this time there is no agreement on where the moral standing should be. One alternative solution would be to use non-viable embryos for research purposes. For context, a non-viable embryo is one that would not fully adhere to the uterus and correctly develop. However, there are drawbacks to this approach, as the research findings will not be as easily translated for use on a viable embryo.

A third ethical issue is one of accessibility. With germline editing, scientists have the potential to edit aspects of human beings that aren't physical. We have probabilistic arguments for where specific cognitive traits of individuals reside within their DNA ^[13]. With the right technology, this has the potential to improve a person's intelligence or cognitive abilities. It is worthwhile to consider the potential outcomes of implementing this procedure. This type of genetic modification is costly, and its availability would be limited to those with higher socioeconomic status. This could lead to discrimination in establishing who has enhanced cognitive ability and who does not.

COLLABORATIVE EXERCISE: The increasing widespread use of genome editing can also create unwanted societal changes and stigmas. Because genomic engineering focuses on either disease curative or genetic enhancement processes, it creates this notion that this "new person" that they have become is the better version of themselves. This can lead to a general stigma of society becoming less accepting of people who are different, and would only widen the gap of socioeconomic statuses. (https://medlineplus.gov/genetics/understanding/therapy/ethics/)

Beyond Ethical Concerns

Genomic editing causes long-term cascading effects through the gene pool of the embryo that had their genes changed. Changes like this are banned in much of the world because the concern for how it could affect the descendants of this genetic pool. There are legal arguments to say that it was implied consent of the embryo when the treatment was done, but who decided what treatment was completed.

https://www.nature.com/articles/s41599-020-0399-2#Sec4

References

1. ↑ Carroll, D. (2021) A short, idiosyncratic history of genome editing, Gene and Genome Editing. Elsevier. Available at: https://www.sciencedirect.com/science/article/pii/S2666388021000022
2. ↑ Carroll, D. (2021) A short, idiosyncratic history of genome editing, Gene and Genome Editing. Elsevier. Available at: https://www.sciencedirect.com/science/article/pii/S2666388021000022
3. ↑ CRISPR timeline (2018) Broad Institute. Available at: https://www.broadinstitute.org/what-broad/areas-focus/project-spotlight/crispr-timeline
4. ↑ CRISPR timeline (2018) Broad Institute. Available at: https://www.broadinstitute.org/what-broad/areas-focus/project-spotlight/crispr-timeline
5. ↑ Brooks, P.J. (2022) Somatic cell genome editing program, National Center for Advancing Translational Sciences. U.S. Department of Health and Human Services. Available at: https://ncats.nih.gov/somatic
6. ↑ Bergman, M.T. (2022) Harvard researchers share views on future, ethics of gene editing, Harvard Gazette. Harvard Gazette. Available at: https://news.harvard.edu/gazette/story/2019/01/perspectives-on-gene-editing/
7. ↑ Baylis, F. et al. (2020) Human Germline and heritable genome editing: The ... - The CRISPR Journal, Human Germline and Heritable Genome Editing: The Global Policy Landscape. Available at: https://www.liebertpub.com/doi/10.1089/crispr.2020.0082
8. ↑ Bergman, M.T. (2022) Harvard researchers share views on future, ethics of gene editing, Harvard Gazette. Harvard Gazette. Available at: https://news.harvard.edu/gazette/story/2019/01/perspectives-on-gene-editing/
9. ↑ Liu, S. (2020) Legal reflections on the case of genome-edited babies - global health research and policy, BioMed Central. BioMed Central. Available at: https://ghrp.biomedcentral.com/articles/10.1186/s41256-020-00153-4#:~:text=In%20the%20USA%2C%20Human%20genome,Institutes%20of%20Health%20(NIH).
10. ↑ Liu, S. (2020) Legal reflections on the case of genome-edited babies - global health research and policy, BioMed Central. BioMed Central. Available at: https://ghrp.biomedcentral.com/articles/10.1186/s41256-020-00153-4#:~:text=In%20the%20USA%2C%20Human%20genome,Institutes%20of%20Health%20(NIH).
11. ↑ Howard, H. and Niemiec, E. (2020) Ethical issues related to research on genome editing in human embryos, Computational and Structural Biotechnology Journal. Elsevier. Available at: https://www.sciencedirect.com/science/article/pii/S2001037019305173
12. ↑ Paull, D. et al. (2012) Nuclear genome transfer in human oocytes eliminates mitochondrial DNA variants, Nature News. Nature Publishing Group. Available at: https://www.nature.com/articles/nature11800
13. ↑ de Araujo, M. (2020) The ethics of genetic cognitive enhancement: Gene editing or embryo selection?, MDPI. Multidisciplinary Digital Publishing Institute. Available at: https://www.mdpi.com/2409-9287/5/3/20