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What if gene editing veers from being therapeutic to an enhancement tool for human traits?

In October of this year, University of California at Berkeley biochemist Dr. Jennifer Doudna and Dr. Emmanuelle Charpentier, Director of the Max Planck Institute for Infection Biology in Berlin, won the 2020 Nobel Prize in Chemistry. They were awarded the prize for their co-development of CRISPR-Cas9, a genome editing breakthrough that has revolutionized biomedicine, allowing scientists to rewrite DNA efficiently and precisely. The power of CRISPR-Cas9 has opened up new possibilities from agriculture to medicine, and has the potential to be utilized for treatment of thousands of human diseases.

The technology is a simple yet powerful tool for editing the human genome, allowing researchers to easily alter DNA sequences and modify gene function, like a find and replace system.

- Janice Berliner, 2020

CRISPRs (clusters of regularly interspaced short palindromic repeats) are specialized stretches of DNA, and the Cas9 protein is an enzyme that acts like a pair of molecular scissors, capable of cutting strands of DNA. The technology is a simple yet powerful tool for editing the human genome, allowing researchers to easily alter DNA sequences and modify gene function, like a find and replace system.

The human genome encodes a series of messages and instructions within the DNA sequence that tells the body how to grow, make enzymes and proteins, and determine susceptibility to certain diseases and conditions. Genome editing involves changing those sequences and the messages they encode, and CRISPR-Cas9 is smart enough to be targeted, rather than cutting anywhere in the genome. Studies using laboratory and animal models of human disease have demonstrated that this technology can be effective in correcting genetic conditions, such as cystic fibrosis, cataracts and muscular dystrophy, paving the way for therapeutic applications in human beings. It is also being used in crops to improve yield, drought tolerance and nutritional properties.

For all its potential, CRISPR-Cas9 is not without its drawbacks. While scientists can supply the DNA template of their choosing and write in any gene they want, pieces of DNA may be accidentally inserted or deleted, resulting in mutations. Other "off-target" effects can also occur, in which DNA is cut at sites other than what was intended. So naturally, the many potential applications of CRISPR technology raise questions about the ethical merits and consequences of tampering with our genome.

Another dilemma occurs in the consideration of modifying genes in human embryos and reproductive cells (sperm and eggs). Since changes to these cells can be passed on to subsequent generations, using CRISPR technology to make these germ-line edits has raised a number of ethical concerns. Because our knowledge of human genetics, gene-environment interactions, and the pathways and interactions of diseases, we are limited in our ability to control for any unintended consequences that could occur for future generations. Should we make changes that could fundamentally affect future generations without having their consent? There are guidelines and recommendations for genome editing, but of course this is cautionary and not legal prohibition.

Finally, many argue that germ-line editing should only be done (if at all) with genes that lead to serious diseases, and only when there are no other reasonable treatment alternatives. What if the use of germ-line editing veers from being a therapeutic tool to an enhancement tool for various human characteristics? As with most things, to go along with the incredible advances in science and medicine, there are always risks with technology. Until we improve the technology and carefully consider the ethics, embryo editing of any kind should be off the table.

For those who would like more information, these should be helpful:

https://academic.oup.com/jlb/article/6/1/111/5549624

https://www.amazon.com/Ethical-Dilemmas-Genetics-Genetic-Counseling/dp/019994489X/ref=pd_rhf_se_p_img_8?_encoding=UTF8&psc=1&refRID=8AT8HH2H9BTXH7SZ7R00


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