Ethical Implications of Human Genetic Engineering | SAGE

DNA editing techniques have been available for decades and are crucial tools for understanding gene functions and molecular pathways. Recently, genome editing has stepped back into the limelight because of newer technologies that can quickly and efficiently modify genomes by introducing or genetically correcting mutations in human cells and animal models. These tools include Zinc Finger Nucleases (ZFNs), Transcription activator-like effector nucleases (TALENs), and the most recent player to join the ranks, Clustered Regularly Interspaced Short Palindromic repeats (CRISPR) (here, here). In a short time span, CRISPR/Cas9 has completely revolutionized the understanding of protein function, disease modeling, and potential therapeutic applications.

BACKGROUND on CRISPR/Cas9

The CRISPR/Cas9 system functions similarly to ZFNs and TALENs, it also takes advantage of a cells DNA repair machinery to delete (knock-out) or add in (knock-in) sequences of DNA. However, CRISPR/Cas9 offers several advantages: it is easier to target a specific gene of interest since designing the required CRISPR component is simple and efficient, whereas generating ZFNs and TALENs is more time consuming; it is often more proficient in generating the desired recombination results; and it is exponentially more cost effective, so almost any laboratory in the world can use it. CRISPR/Cas9 has been shown to work in several model organisms, and consequently researchers are keen to apply this technology for modifying genetic mutations in humans with uncured diseases as well as in human embryos, which arouses many scientific and ethical considerations.

Human embryonic gene editing

Genome editing technologies have come a long way and have already advanced towards mammalian models and clinical trials in humans. Recently, genetic modification of human embryos using CRISPR/Cas9 technology was achieved by the Huang laboratory in China in April 2015. They genetically modified un-viable embryos obtained from an in vitro fertilization clinic. These embryos were fertilized with two different sources of sperm, thus impairing their development. In this study, the Huang group repaired a mutation in the human -globin gene (HBB) that causes the blood disorder -thalassaemia. The CRISPR/Cas9 system and a donor DNA sequence containing the normal, healthy version of the HBB were injected into 86 embryos. A total of four embryos successfully integrated the corrected version of the HBB at the appropriate site. However, the authors reported a high number of off-target effects, meaning that CRISPR/Cas9 modified other locations in the genome; a non-ideal situation that could cause the disruption of other essential gene functions. The study demonstrated two important findings: genetic engineering is possible in human embryos and the CRISPR/Cas9 system requires essential improvements before it can be used in future studies on human embryos. More importantly, these results force scientists to question the future and the implications of such a powerful technology. Should we accept genetic engineering of human embryos? If yes, when and in what capacity should we accept it?

Current guidelines and regulation

Scientists in the United States are addressing the need for regulation of human embryonic gene editing. On April 29th, the US National Institute of Health (NIH) director, Dr. Francis Collins, released a statement emphasizing the bureaus policy against funding research involving genome editing of human embryos and the ethical concerns regarding this technology. However, the policy does not necessarily cover privately funded projects.

Safety regarding genetic engineering is a major concern and Huangs publication highlights this point. However, this publication forces the community to address whether scientists should use non-viable or discarded embryos to improve the efficiency and efficacy of the CRISPR/Cas9 system. The CRISPR/Cas9 system was developed for human genome targeting in 2012 and since then has seen rapid improvements. If it is decided that unviable embryos can be used for this type of research, the next step for US lawmakers is to evaluate new guidelines for the funding and safety of genetic engineering in these embryos.

Ethical concerns

While the interest and use of CRISPR/Cas9 has exploded since its discovery in 2012, prominent scientists in the field have already initiated conversations regarding the ethical implications that arise when modifying the human genome. Preventing genetic diseases by human genetic engineering is inevitable. The slippery slope is when/if we start to use it for cosmetic changes such as eye color or for improving a desired athletic trait. A perfect example is surgery, which we have performed for hundred years for disease purposes and is now widely used as a cosmetic tool. Opening the doors for genetic engineering of human embryos could with time lead to manipulate genetics for desirable traits, raising the fear of creating a eugenic driven human population.

Who are we to manipulate nature? However, for all those who suffer from genetic diseases the answer is not so simples; if we can safely prevent severe genetic diseases and create healthy humans, why not manipulate nature? Have we not already done this in other animal populations? At this time the long term effects of genome editing remain unknown, raising additional questions. As the field progresses, with appropriate regulations and guidelines it will eventually co-exist alongside other major controversial topics including nuclear power and genetically modified organisms. Since ethics are different across the world, creating international guidelines will be a challenge, but a necessity. Strict regulations are in place for nuclear power, the same should be possible for genetic engineering of human embryos. To outlaw genetic engineering entirely will be potentially declining a place at the discussion table, as the further utilization of CRISPR/Cas9 technology is unlikely to be abandoned.

This fall The National Academy of Sciences and National Academy of Medicine, together with CRISPR/Cas9 discoverers Dr. Jennifer Doudna, Dr. Emmanuelle Charpentier, and other leading scientist within the field are organizing an international summit to consider all aspects (both ethical and scientific) of human genetic engineering to develop standard guidelines and policies for practicing human genome editing. The NIH already has guidelines in place, and will potentially add more as a result of this summit. It is expected that other countries will have varying guidelines for human genomic engineering. Also, to avoid fear and misunderstanding, scientists will need to convey human genome editing in a responsible manner to the general human population. This summit is a step in the right direction encouraging caution and regulations. Hence, there is now a need for a timely but thoughtful set of guidelines for the general scientific community as well as for the broader human community.

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Ethical Implications of Human Genetic Engineering | SAGE

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