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Human germline engineering is the process by which the genome of an individual is edited in such a way that the change is heritable. You deliberately change the genes that are passed on from parents to children. This is achieved through genetic alterations within the germinal cells, or the reproductive cells, such as the oocyte and spermatogonium. 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.

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. 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. 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.

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.

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.

Conceivable uses

Currently, there are no successfully engineered humans, but 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. Mutations in the HBB gene result in the disorder β-thalassaemia, which can be fatal. 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. In an extreme case, people would be able to effectively create the offspring that they want, with traits 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. 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.

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. 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. In recent years, as new founding is known as "gene editing" or "genome editing" has promted 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 of 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.

Ethical and moral debates

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. 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. 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. 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. 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. 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.

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. 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.

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. 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. 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.

See also

• Gene therapy
• Germinal choice technology

References

1. ^ 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.
2. ^ Cyranoski, David; Reardon, Sara. "Chinese scientists genetically modify human embryos". Nature. doi:10.1038/nature.2015.17378.
3. ^ Callaway, Ewen. "Second Chinese team reports gene editing in human embryos". Nature. doi:10.1038/nature.2016.19718.
4. 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.
5. ^ 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.
6. Lock, Margaret; Nichter, Mark (2003-09-02). New Horizons in Medical Anthropology: Essays in Honour of Charles Leslie. Routledge. ISBN 9781134471287.
7. 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.
8. 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.
9. ^ Ishii, Tetsuya (August 2014). "Potential impact of human mitochondrial replacement on global policy regarding germline gene modification". Reproductive Biomedicine Online. 29 (2): 150–155. doi:10.1016/j.rbmo.2014.04.001. ISSN 1472-6491. PMID 24832374.
10. ^ Cole-Turner, Ronald (2008). Design and Destiny: Jewish and Christian Perspectives on Human Germline Modification. MIT Press. ISBN 9780262533010.
11. ^ Stock, Gregory (2003). Redesigning Humans: Choosing Our Genes, Changing Our Future. Houghton Mifflin Harcourt. ISBN 0618340831.
12. ^ "Germ-line gene modification and disease prevention: Some me - ProQuest". search.proquest.com. Retrieved 2017-06-09.
13. ^ "A slippery slope to human germline modification - ProQuest". search.proquest.com. Retrieved 2017-06-09.
14. Krause, Kenneth W. (2017). "Editing the Human Germline: Groundbreaking Science and Mind-Numbing Sentiment". Skeptical Inquirer. 41 (6): 29–31.

• Genetics