Embryonic Genomic Engineering

Genomic editing is a 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 . 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. Questions of debate surrounding the subject today include: 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? 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 . 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 . 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 . 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 is projected to develop further.

Types of Genomic Editing

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.

Germline Gene Editing

Germline editing is done on "early-stage embryos, gametes (eggs and sperm), or germ cells that are the precursors of gametes" . 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.

Germline vs Somatic Gene Editing in a Clinical Setting

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. In these procedures, 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” . 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” . Although determined unethical, the results of this experiment showed implications for the impacts of germline editing in a clinical setting.

Ethical Implications

Side Effects

An 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" . 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 . This criterion is a consideration in germline editing research.

Moral Concerns

An 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. Individuals debate whether the embryo should be regarded in the same way that we regard a human being or if they should be regarded as merely a collection of cells. If considered as a human being, then conducting experiments in which the genome is altered while ignoring the consequences would be considered unethical. In contrast, if considered to be cells, then it is of equivalence to experimenting on any human tissue cell; a process 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.

Accessibility

An ethical issue is one of accessibility in genomic editing. Currently, genetic therapies range between $373,000 and $2.1 million in cost . These therapies provide treatments for diseases that are genetically based. The cost of these therapies is high, limiting the individuals who are able to have access to them. This creates an economical divide in the healthcare system comparing those who are able to access genomic editing technologies versus those who can not.

Eugenics

Definition

Eugenics is the idea that as a society, the quality of the human race can be improved through controlling hereditary aspects . This term was coined by Francis Galton in the late nineteenth century and was used as justification for "morally reprehensible acts" . Genes that are considered to be harmful would be removed and those considered to be positive would be maximized. Individuals genes containing disabilities or heritable diseases would be eliminated from the gene pool inhibiting their proliferation. This removes variability in the genomic diversity of the human race shifting society towards one without many genetic differences.

Implications Today

In modern times as CRISPR-Cas9 and other genomic technology develops, the controversy resurfaces in prevalence. There is no formal definition for what is considered the "best" quality of life or what genes are considered to be "good" or "bad". This disagreement can lead to problematic implications. This implies ranking characteristics of individuals and labeling them in an objective manner. An area where eugenics and its complications becomes prevalent is in preimplantation genetic diagnosis. This is the idea that embryos can be created and edited through in vitro fertilization before implantation . In eugenics context, embryos with genetic impairments would be eliminated. If used in this setting, this type of genomic editing would have potential infringements on reproductive freedom.

Cognitive Enhancement

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 .

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

Discussion

The length of the article is 1500 words, which is 500 words more than the requirement of about 1000 words. I think this is a good thing though, because it shows the student’s commitment to flesh out more ideas and content in their draft.

This article does include the 3 major components of a good article. The author summarizes the issue in the opening paragraph, which gave me both a good idea of the background of the topic as well as a preview of some of the ethical concerns of embryonic genomic engineering. The body of the article was also well organized. It contains four main sections: the history of this field, an explanation of somatic gene editing, an explanation of germline gene editing, and a discussion of ethical implications. The sections on somatic gene editing and germline gene editing were helpful in helping readers understand the differences between the two. One way in which the student could potentially think about finalizing this draft into a final mediawiki is to encompass the sections on somatic gene editing and germline gene editing into one larger section titled something like “Types of Gene Editing” or “Somatic vs Germline Editing”, to clarify to the reader that these sections explain the differences between two very different paradigms in genomic engineering. The author did a great job of backing up their statements with references and reliable sources. The author made sure to include inline citations and even put in quotes what was directly pulled from an external source.

The issue at stake is clear to me. The author addressed many potential ethical consequences and considerations of genomic editing and raised many questions to ponder. Perhaps in the final copy, the author can seek to flesh out some of the major ethical considerations a little bit more. I think that if the author can add some more history revolving around the stated ethical issues, that would make this article even stronger. Another suggestion is that perhaps the author could further divide their section on Ethical Implications into smaller subsections, each discussing a single ethical issue, instead of including all of them in one large section.

The author for the most part does not state personal opinions. And in the one or two times when they do, they are aligned with a popular opinion held by the public, such as “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.” I think the author can try to incorporate more events and public debates into the discussion of ethical issues, such as citing specific situations in which perspectives were argued.