Human germline engineering: Difference between revisions
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Scientists using the CRISPR/cas9 system to modify genetic materials have run into issues when it comes to mammalian alterations due to the complex diploid cells. Studies have been done in microorganisms regarding loss of function genetic screening and some studies using mice as a subject. RNA processes differ between bacteria and mammalian cells and scientists have had difficulties coding for mRNA's translated data without the interference of RNA. Studies have been done using the cas9 nuclease that uses a single guide RNA to allow for larger knockout regions in mice which was successful.<ref>Wang, Tim et al. “Genetic screens in human cells using the CRISPR-Cas9 system” Science vol. 343,6166 (2013): 80-4.</ref> Altering the genetic sequence of mammals has also been widely debated thus creating a difficult FDA regulation standard for these studies. |
Scientists using the CRISPR/cas9 system to modify genetic materials have run into issues when it comes to mammalian alterations due to the complex diploid cells. Studies have been done in microorganisms regarding loss of function genetic screening and some studies using mice as a subject. RNA processes differ between bacteria and mammalian cells and scientists have had difficulties coding for mRNA's translated data without the interference of RNA. Studies have been done using the cas9 nuclease that uses a single guide RNA to allow for larger knockout regions in mice which was successful.<ref>Wang, Tim et al. “Genetic screens in human cells using the CRISPR-Cas9 system” Science vol. 343,6166 (2013): 80-4.</ref> Altering the genetic sequence of mammals has also been widely debated thus creating a difficult FDA regulation standard for these studies. |
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== Ethical and moral debates == |
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As it stands, there is much controversy surrounding human germline engineering. Editing the genes of human embryos is very different, and raises great social and ethical concerns. The scientific community, and global community, are quite divided regarding whether or not human germline engineering should be practiced or not. It is currently banned in many of the leading, developed countries, and highly regulated in the others due to ethical issues.<ref name=":4">{{Cite journal|last=Ishii|first=Tetsuya|date=August 2014|title=Potential impact of human mitochondrial replacement on global policy regarding germline gene modification|journal=Reproductive Biomedicine Online|volume=29|issue=2|pages=150–155|doi=10.1016/j.rbmo.2014.04.001|issn=1472-6491|pmid=24832374}}</ref> The large debate lies in the possibility of eugenics if human germline engineering were to be practiced clinically. This topic is hotly debated because the side opposing human germline modification believes that it will be used to create humans with "perfect", or "desirable" traits.<ref name=":4" /><ref name=":5">{{Cite book|url=https://books.google.com/books?hl=en&lr=&id=E3qsPJb44Q8C&oi=fnd&pg=PR7&dq=human+germline+engineering&ots=8huw0UczmM&sig=P_vkxlt0dpSJFBhCN3DqtSBu6Ck#v=onepage&q=human%20germline%20engineering&f=false|title=Design and Destiny: Jewish and Christian Perspectives on Human Germline Modification|last=Cole-Turner|first=Ronald|date=2008|publisher=MIT Press|isbn=9780262533010}}</ref><ref name=":6">{{Cite book|url=https://books.google.com/books?hl=en&lr=&id=XLjJ4AkYWUgC&oi=fnd&pg=PR7&dq=human+germline+engineering&ots=u7U1rBv9-U&sig=PUpUEhxrI-Dl6pXNfecYeIeDAOs#v=onepage&q=human%20germline%20engineering&f=false|title=Redesigning Humans: Choosing Our Genes, Changing Our Future|last=Stock|first=Gregory|date=2003|publisher=Houghton Mifflin Harcourt|isbn=0618340831}}</ref><ref name=":7">{{Cite web|url=http://search.proquest.com/openview/87f48e99f9751939f95b6c2a3a18fa69/1?pq-origsite=gscholar&cbl=1256|title=Germ-line gene modification and disease prevention: Some me - ProQuest|website=search.proquest.com|access-date=2017-06-09}}</ref><ref name=":8">{{Cite web|url=http://search.proquest.com/openview/153890ac6d6289c595fb772a4602c1b2/1?pq-origsite=gscholar&cbl=40569|title=A slippery slope to human germline modification - ProQuest|website=search.proquest.com|access-date=2017-06-09}}</ref> Those in favor of human germline modification see it as a potential medical tool, or a medical cure for certain diseases that lie within the genetic code.<ref name=":5" /> There is a debate as to if this is morally acceptable as well. Such debate ranges from the ethical obligation to use safe and efficient technology to prevent disease to seeing actual benefit in genetic disabilities.<ref>{{cite journal |last1=Krause |first1=Kenneth W. |title=Editing the Human Germline: Groundbreaking Science and Mind-Numbing Sentiment |journal=[[Skeptical Inquirer]] |date=2017 |volume=41 |issue=6 |pages=29–31}}</ref> While typically there is a clash between religion and science, the topic of human germline engineering has shown some unity between the two fields. Several religious positions have been published with regards to human germline engineering. According to them, many see germline modification as being more moral than the alternative, which would be either discarding of the embryo, or birth of a diseased human.<ref name=":5" /><ref name=":7" /><ref name=":8" /> The main conditions when it comes to whether or not it is morally and ethically acceptable lie within the intent of the modification, and the conditions in which the engineering is done. |
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Another very interesting point on the debate of whether or not it is ethical and moral to engineer the human germline is a perspective of looking at past technologies and how they have evolved. Dr. Gregory Stock discusses the use of several diagnostic tests used to monitor current pregnancies and several diagnostic tests that can be done to determine the health of embryos.<ref name=":6" /> Such tests include amniocentesis, ultrasounds, and other preimplantation genetic diagnostic tests. These tests are quite common, and reliable, as we talk about them today; however, in the past when they were first introduced, they too were scrutinized.<ref name=":6" /> |
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One of the main arguments against human germline engineering lies in the ethical feeling that it will dehumanize children. At an extreme, parents may be able to completely design their own child, and there is a fear that this will transform children into objects, rather than human beings.<ref name=":6" /><ref name=":7" /><ref name=":8" /> There is also a large opposition as people state that by engineering the human germline, there is an attempt at "playing God", and there is a strong opposition to this. One final, and very possible issue that causes a strong opposition of this technology is one that lies within the scientific community itself. Inevitably, this technology would be used for enhancements to the genome, which would likely cause many more to use these same enhancements. By doing this, the genetic diversity of the human race and the human gene pool as we know it would slowly and surely diminish.<ref name=":6" /> Despite the controversy surrounding the topic of human germline engineering, it is slowly and very carefully making its way into many labs around the world. These experiments are highly regulated, and they do not include the use of viable human embryos, which allows scientists to refine the techniques, without posing a threat to any real human beings.<ref name=":6" /> |
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== See also == |
== See also == |
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Revision as of 18:45, 2 December 2018
Human germline engineering is the process by which the genome of an individual is edited in such a way that the change is heritable. This is achieved through genetic alterations within the germinal cells, or the reproductive cells, such as the oocyte and spermatogonium.[1] Human germline engineering should not be confused with gene therapy. Gene therapy consists of altering somatic cells, which are all cells in the body that are not involved in reproduction. While gene therapy does change the genome of the targeted cells, these cells are not within the germline, so the alterations are not heritable and cannot be passed on to the next generation.[1]
The first attempt to edit the human germline was reported in 2015, when a group of Chinese scientists used the gene editing technique CRISPR/Cas9 to edit single-celled, non-viable embryos to see the effectiveness of this technique.[2] This attempt was rather unsuccessful; only a small fraction of the embryos successfully spliced the new genetic material and many of the embryos contained a large amount of random mutations.[2][3] The non-viable embryos that were used contained an extra set of chromosomes, which may have been problematic. In 2016, another similar study was performed in China which also used non-viable embryos with extra sets of chromosomes. This study showed very similar results to the first; there were successful integrations of the desired gene, yet the majority of the attempts failed, or produced undesirable mutations.[3]
The most recent, and arguably most successful, experiment in August 2017 attempted the correction of the heterozygous MYBPC3 mutation associated with Hypertrophic Cardiomyopathy in human embryos with precise CRISPR–Cas9 targeting. 52% of human embryos were successfully edited to retain only the wild type normal copy of MYBPC3 gene, the rest of the embryos were mosaic, where some cells in the zygote contained the normal gene copy and some contained the mutation.[4]
Human genetic modification is the direct manipulation of the genome using molecular engineering. The two different types of gene modification is "somatic gene modification" and "germline genetic modification. Somatic gene modification adds, cuts, or changes the genes in cells of a living person. Germline gene modification changes the genes in sperm, eggs, and embryos. These modifications would appear in every cell of the human body. Germline modification is yet to be done to a human.[5]
CRISPR/cas9
CRISPR/cas9 is a genome editing tool that allows scientists to edit the genome by adding or removing sections of DNA. It contains an enzyme and RNA, the enzyme acting like scissors to alter the DNA while the RNA acts as a guide for those enzymes. This system is currently the fastest and cheapest way to genetically engineer on the market today and it's uses are endless. The RNA in the CRISPR/cas9 allows researchers to target specific sequences in the genome making it possible for them to alter one sequence and not the others surrounding them. This is a new technology for scientists in the genomic altering field.[6]
Although the CRISPR/cas9 cannot yet be used in humans, it allows scientists to target genes more effectively in diploid cells of mammals in order to one day be used in human research. Clinical trials are being conducted on somatic cells, but CRISPR could make it possible to modify the DNA of spermatogonial stem cells. This could eliminate certain diseases in human, or at least significantly decrease a disease's frequency until it eventually disappears over generations.[7] Cancer survivors theoretically would be able to have their genes modified by the CRISPR/cas9 so that certain diseases or mutations will not be passed down to their offspring. This could possibly eliminate cancer predispositions in humans.[7] Researchers hope that they can use the system in the future to treat currently incurable diseases by altering the genome altogether.
Conceivable uses
The Berlin Patient has a genetic mutation in the CCR5 gene (which codes for a protein on the surface of white blood cells, targeted by the HIV virus) that deactivates the expression of CCR5, conferring innate resistance to HIV. HIV/AIDS carries a large disease burden and is incurable (see Epidemiology of HIV/AIDS). One proposal is to genetically modify human embryos to give the CCR5 Δ32 allele to people.
There are many prospective uses such as curing genetic diseases and disorders. If perfected, somatic gene editing can promise helping people who are sick. In the first study published regarding human germline engineering, the researchers attempted to edit the HBB gene which codes for the human β-globin protein.[2] Mutations in the HBB gene result in the disorder β-thalassaemia, which can be fatal.[2] Perfect editing of the genome in patients who have these HBB mutations would result in copies of the gene which do not possess any mutations, effectively curing the disease. The importance of editing the germline would be to pass on this normal copy of the HBB genes to future generations.
Another possible use of human germline engineering would be eugenic modifications to humans which would result in what are known as "designer babies". The concept of a "designer baby" is that its entire genetic composition could be selected for.[8] In an extreme case, people would be able to effectively create the offspring that they want, with a genotype of their choosing. Not only does human germline engineering allow for the selection of specific traits, but it also allows for enhancement of these traits.[8] Using human germline editing for selection and enhancement is currently very heavily scrutinized, and the main driving force behind the movement of trying to ban human germline engineering.[9]
The ability to germline engineer human genetic codes would be the beginning of eradicating incurable diseases such as HIV/AIDS, sickle-cell anemia and multiple forms of cancer that we cannot stop nor cure today.[10] Scientists having the technology to not only eradicate those existing diseases but to prevent them altogether in fetuses would bring a whole new generation of medical technology. There are numerous disease that humans and other mammals obtain that are fatal because scientists have not found a methodized ways to treat them. With germline engineering, doctors and scientists would have the ability to prevent known and future diseases from becoming an epidemic.
State of research
The topic of human germline engineering is a widely debated topic. It is formally outlawed in more than 40 countries. Currently, 15 of 22 Western European nations have outlawed human germline engineering.[11] Human germline modification has for many years has been heavily off limits. There is no current legislation in the United States that explicitly prohibits germline engineering, however, the Consolidated Appropriation Act of 2016 banned the use of U.S. Food and Drug Administration (FDA) funds to engage in research regarding human germline modifications.[12] In recent years, as new founding is known as "gene editing" or "genome editing" has promoted speculation about their use in human embryos. In 2014, it has been said about researchers in the US and China working on human embryos. In April 2015, a research team published an experiment in which they used CRISPR to edit a gene that is associated with blood disease in non-living human embryos. All these experiments were highly unsuccessful, but gene editing tools are used in labs.
Scientists using the CRISPR/cas9 system to modify genetic materials have run into issues when it comes to mammalian alterations due to the complex diploid cells. Studies have been done in microorganisms regarding loss of function genetic screening and some studies using mice as a subject. RNA processes differ between bacteria and mammalian cells and scientists have had difficulties coding for mRNA's translated data without the interference of RNA. Studies have been done using the cas9 nuclease that uses a single guide RNA to allow for larger knockout regions in mice which was successful.[13] Altering the genetic sequence of mammals has also been widely debated thus creating a difficult FDA regulation standard for these studies.
See also
References
- ^ a b Stock, Gregory; Campbell, John (2000-02-03). Engineering the Human Germline: An Exploration of the Science and Ethics of Altering the Genes We Pass to Our Children. Oxford University Press. ISBN 9780195350937.
- ^ a b c d Cyranoski, David; Reardon, Sara. "Chinese scientists genetically modify human embryos". Nature. doi:10.1038/nature.2015.17378.
- ^ a b Callaway, Ewen. "Second Chinese team reports gene editing in human embryos". Nature. doi:10.1038/nature.2016.19718.
- ^ Ma, Hong; Marti-Gutierrez, Nuria; Park, Sang-Wook; Wu, Jun; Lee, Yeonmi; Suzuki, Keiichiro; Koski, Amy; Ji, Dongmei; Hayama, Tomonari (August 2017). "Correction of a pathogenic gene mutation in human embryos". Nature. 548 (7668): 413–419. doi:10.1038/nature23305. ISSN 1476-4687.
- ^ "About Human Germline Gene Editing". Centers for Genetics and Society. Center for Genetics and Society. Retrieved 12 November 2018.
- ^ “What Is CRISPR-Cas9?” Facts, The Public Engagement Team at the Wellcome Genome Campus, 19 Dec. 2016, www.yourgenome.org/facts/what-is-crispr-cas9.
- ^ a b Katz, Gregory; Pitts, Peter J. (2017-08-18). "Implications of CRISPR-Based Germline Engineering for Cancer Survivors". Therapeutic Innovation & Regulatory Science. 51 (6): 672–682. doi:10.1177/2168479017723401. ISSN 2168-4790.
- ^ a b National Academies of Sciences, Engineering, and Medicine. 2017. Human Genome Editing: Science, Ethics, and Governance. Washington, DC: The National Academies Press. doi: 10.17226/24623.
- ^ Lock, Margaret; Nichter, Mark (2003-09-02). New Horizons in Medical Anthropology: Essays in Honour of Charles Leslie. Routledge. ISBN 9781134471287.
- ^ Lanphier, Edward, et al. “Don't Edit the Human Germ Line.” Nature News, Nature Publishing Group, 12 Mar. 2015, www.nature.com/news/don-t-edit-the-human-germ-line-1.17111
- ^ Lanphier, Edward; Urnov, Fyodor; Haecker, Sarah Ehlen; Werner, Michael; Smolenski, Joanna (2015-03-26). "Don't edit the human germ line". Nature. 519 (7544): 410–411. doi:10.1038/519410a.
- ^ Cohen, I. Glenn; Adashi, Eli Y. (2016-08-05). "The FDA is prohibited from going germline". Science. 353 (6299): 545–546. doi:10.1126/science.aag2960. ISSN 0036-8075. PMID 27493171.
- ^ Wang, Tim et al. “Genetic screens in human cells using the CRISPR-Cas9 system” Science vol. 343,6166 (2013): 80-4.
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