Friday, November 18, 2016

CRISPR

CRISPR is a relatively new term that describes new discoveries and new technology in the world of genetics. CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats and refers to short repetitions of base pair sequences in bacterial genomes which naturally occur as part of bacterial genetic defence mechanisms against invading viruses. These CRISPR sequences are used by bacteria to store genetic memories of past viral invasions that might otherwise lead to the destruction of the bacterial cell. Next to a CRISPR sequence is a segment of DNA that represents part of a viral genome from a previous encounter with that virus. It is like the bacteria store a photo of all of the viruses that previously tried to kill them and then recognize that virus when it shows up again. Cas9 enzymes search through the cell for these potentially dangerous pieces of DNA and then make RNA copies that will guide the Cas9 enzyme to the dangerous viral DNA and cut it in two so that the virus is defeated. If a new virus shows up, Cas9 first makes a copy of the new viral genome and inserts it in between the CRISPR sequences so that it is ready for the next time this virus tries to invade.

This biological system within the cells of bacteria has been exploited and used by genetic scientists to create a tool that can be used to edit the genome of humans and other research subjects. So, you may also hear people refer to CRISPR technology as it is used for gene editing in medicine and research. Cas9 and other CRISPR enzymes recognize strings of DNA about 20 base-pairs in length and can therefore be engineered to be very specific and targeted. This has allowed researchers to load Cas9 with a specific sequence that can then target where they would like to cut out a piece of DNA, say to knock out a gene and determine what that gene does, knock out a rogue gene that is malfunctioning, or to cut out a defective gene and replace it with a properly functioning gene. Recently, scientists in China used this technology to engineer cells to potentially treat lung cancer. In this case, CRISPR technology was used on immune cells taken from the patients and a gene was disabled. The protein, PD-1, normally slows down or ends an immune response (something that is normally needed but exploited by cancer cells) and so researchers inactivated it so that the body might continue to mount an immune response against the cancer cells in the lungs. This represents the first time CRISPR technology has been used in such a way in human trials.

As one can readily see, this technology has vast implications and has the potential to solve many medical problems. CRISPR could repair the mutation that causes Cystic-Fibrosis in a family’s genetic makeup, or repair the gene that causes genetic forms of colon cancer such as Adenomatous Polyposis Coli (APC). It also brings with it the possibility of ethical challenges. It could be used to substitute the gene for blue eyes in place of the gene for brown eyes (or the opposite exchange); or it could be used to substitute a gene that codes for average height for a gene that codes for exceptional height (really handy if you are trying to build an Olympic basketball team). Taken to logical conclusions, CRISPR technology could be used to build a super-race of humans and even create genetic enhancements that cannot yet be imagined (think real life X-Men mutants). Scientists in China have already published data showing that they had successfully modified the DNA on nonviable human embryos. They could have just as easily been working on viable embryos.

In a future where diseases can be eradicated and enhancements can be made, what becomes of the average person with defects or no enhancements? Should we concern ourselves with this? A few years ago, the movie Gattaca attempted to engage audiences in questions related to such issues. Now, nearly 20 years later, genetic technology has advanced to nearly the point predicted in that movie. What will another 10 years of medical and technological advance look like in our world? How might we prepare now for the ethical questions yet to come?

For further explanation and discussion, read this article on the modification of DNA in nonviable human embryos.

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