What if you could design your future baby? They could be free of genetic disorders, predisposition to future disease, or even have a longer life span. In 1997, the movie GATTACA introduced us to this world of “designer babies”, where genetic manipulation allowed for the creation of the “perfect” human. But what if this science fiction is not so far-fetched? In the past three years, we have seen the genetic manipulation of human embryos, termed germline engineering, become a reality.
But how could you edit the genes of a human? Scientists are now using CRISPR, a defense system found in bacteria. Much like an immune system, it targets and protects the bacteria from foreign invaders like viruses. Now, scientists are using it as a genetic tool to easily alter any piece of DNA in any species. In the past scientists have utilized CRISPR-Cas9, a particular type of CRISPR system, to edit the genome of adult human cells as well as animal embryos, but no research had been done on human embryos.
The first attempts at human embryo editing were led by Junjiu Huang in China in Guangzhou in 2015. They utilized CRISPR-Cas9 to modify genes responsible for beta-thalassemia, a potentially fatal blood disorder caused by a mutation in the human beta-globulin protein. This disease affects the blood cells ability to carry oxygen throughout the body, which can lead to pale skin, weakness, fatigue, anemia and an increased risk of developing abnormal blood clots. The CRISPR-Cas9 system, which binds and cuts DNA at specific locations, are injected into non-viable human embryos at the single cell stage. The complex can specifically target the problematic gene and will replace or repair it, effectively removing the mutation in the gene causing the genetic disorder.
Of course, not all mutations are bad. Human embryo genome editing done by Yong Fan and his team at Guangzhou Medical University in 2016 attempted to use CRISPR-Cas9 not to eliminate a mutation, but to create one in a normal gene. Individuals naturally resistant to HIV carry a mutation in the CCR5 gene which alters a protein and prevents HIV from infecting human cells. By injecting CRISPR-Cas9 into non-viable human embryos at the single cell stage they attempted to introduce this helpful mutation in a normal cell.
Being able to correct a genetic disorders or create resistance to a problematic disease seems like an amazing stride for science. But science does not always go the way we hypothesize. In theory, replacing a gene in a single-cell, fertilized human embryo would result in all cells produced from the embryo having the repaired gene with no other alterations or consequences. The CRISPR-Cas9 system locates the target DNA, cuts the DNA out like a pair of microscopic scissors, and then replace it with the desired DNA sequence to patch up the hole. However, both experiments revealed obstacles in using this method to genome edit. By giving the cells the genes for CRISPR-Cas9, the cell can continuously create the proteins responsible for cutting the DNA and editing it which can lead to issues. First, off target mutations were found; these are unintended, potentially harmful mutations outside of the target gene. Second, genetic mosaics occurred when the single cell divides to create more cells, where one cell may have the altered gene while another cell does not. If not all cells carry the altered gene there is still risk for genetic disorders or disease to occur. But scientists don’t give up easily.
The third documented attempt by Shoukhrat Mitalipov and his group, and first in the United States, was done this year in Portland, Oregon at the Oregon Health and Science University. Their group attempted to correct a mutation in gene MYBPC3, which causes heart muscle to thicken leading to hypertrophic cardiomyopathy. Using single cell non-viable human embryos not destined for implantation they injected the CRISPR-Cas9 system to correct the gene mutation. Unlike the previous attempts, this work overcame the two major safety hurdles of using CRISPR-Cas9 in human gene therapy. The previous attempts injected the DNA encoding for the CRISPR-Cas9 components, relying on host cells to create the proteins, which allowed for a higher chance of off-target mutations as the CRISPR-Cas9 system was continually present in the cell. Mitalipov and his group, injected just the proteins of the CRISPR-Cas9 system. You can either give a man a fish and feed him for a day, or teach a man how to fish and feed him for a lifetime. Mitalipov and his group simply gave the cell CRISPR, while previous attempts taught the cell how to create CRISPR continuously. By injecting just the proteins they had more control over how long the CRISPR-Cas9 system could operate in the cell, guaranteeing the proteins would be destroyed within in a short period of time. Of 58 embryos edited successfully, only one embryo generated a mosaic, and no off-target mutations were found. While this is a step in the right direction, more tests will need to be done with different mutations to see if these results can be replicated outside of the MYBPC3 gene.
Will we see GATTACA become a reality soon? While these research efforts may show that gene editing in human embryos is possible, and potentially free of consequence, many hurdles still stand between us and GATTACA. First, we will not see clinical trials any time soon for the use of CRISPR-Cas9 in gene editing. Congress has prohibited the U.S. Food and Drug Administration from even reviewing applications for clinical trials involving embryo editing. Any genome modification of human embryos is already banned or highly regulated by law in many countries. The ethical debate itself surrounding edited human embryos has divided scientists on whether we should even continue such research. The fear of designer babies, forever altering the genetic makeup of an individual without their consent, and the potential exploitation of non-therapeutic modifications are just a few of the dilemmas surrounding genetic modification of human embryos. GATTACA shows the possibilities of genetically modifying embryos, but does the reward of potential disease elimination outweigh the fear of ethical consequences associated with designer human babies?
About the Author
|A native Virginian (GO HOKIES!), Caitlin Reeves is a PhD candidate in the Microbiology department studying attachment of the human respiratory pathogen Mycoplasma pneumoniae to its human host. Outside of the lab she can be found planning events for UGA’s Women in Science (WiSci) organization, snuggling with her labradoodle Sherlock, or playing video games despite being a 26 year old “adult”.