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CRISPR: Engineering evolution

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CRISPR: Engineering evolution

The ethical dilemma of enhancing our genes

What if you could ensure your child would never get Crohn’s disease? Or what if you could choose their hair colour? Or make sure they would have perfect eyesight? What may seem like science fiction to us now is just the beginning of what could be possible due to CRISPR, a new gene-editing tool that is sweeping the field of biology.

CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats, and it is a piece of DNA that can be paired with the Cas9 enzyme to modify genes. The CRISPR/Cas9 system was discovered in Jennifer Doudna’s lab in 2012 at the University of California, Berkeley, in collaboration with Emmanuelle Charpentier. It uses a template of RNA designed by scientists to lead the Cas9 to the targeted gene and effectively alter it.

One way to use CRISPR is to simply cut the DNA using the Cas9 protein and the RNA, after which the body’s own repair enzymes will fix the break. This method has its own merits, but the second major use is the one which is gaining more attention.

CRISPR Diagram
Applications of the CRISPR process. Illustration by Alley MacLean

“If you want to replace something — which is the exciting part of this new technology — with a correction, then you need a third element: that piece of DNA with the correct sequence in it,” said Elizabeth Simpson, professor in the department of medical genetics at the University of British Columbia.

Simpson said this technique can be used on both somatic and germline cells, meaning certain modifications are able to be inherited and move through an entire population. This gives CRISPR scientists the ability to prevent genetic disorders; things such as cystic fibrosis and sickle-cell anemia have the potential to become extinct in future generations.

Endless abilities 

Treatment of hereditary diseases isn’t the only area that could see an advancement from CRISPR. Many researchers are already looking at ways to incorporate this knowledge into medical breakthroughs such as cancer treatments, eradication of infections such as malaria, and even a cure for HIV.

Not only is CRISPR opening up a realm of new possibilities related to genetic engineering, but it has also vastly improved previous technologies that tried to achieve similar results. Simpson, who mainly does her experiments with mice, said where previous experiments would take a year and a half and yield only a 60 per cent success rate, CRISPR now allows her to do similar tests in half the time with an accuracy of 95 per cent.

“It’s easier, it’s quicker, (and) it’s more reliable,” she said, adding that while previous technology allowed her to edit the genomes of mice, it wasn’t possible in other animals like squirrels or rabbits.

This technology has changed that. “A cell is a cell from the point of view of CRISPR. That was not true of the other technologies we have.”

Like any other technology, there are still limitations involved. A drawback specific to CRISPR is the opportunity for “off-targeting” to occur. This is when the system accidentally alters something that it didn’t intend to, creating a mutation. Usually, this happens because the RNA pattern is very similar to the one the system is trying to find.

Simpson explains that most scientists are finding CRISPR to have a relatively low frequency of this, but it is still something researchers have to consider, especially before the technology is made more accessible.

Ethical dilemma 

Naturally, technology of this scale has started a conversation about ethics both inside and outside the scientific community. With CRISPR still being relatively new, its capabilities are constantly being pushed and reimagined.

“This is the kind of nature of science; it consistently gives us these new abilities that raises moral questions that we’ve never had to confront before,” said Alain Beauclair, an ethics professor at MacEwan University. “We have these Jurassic Park-type questions: ‘Are we playing God?’”

A common fear about CRISPR is that it could take society down the road of eugenics, with certain people deciding the traits they would like to see more of in their lineage. The term “designer babies” is gaining traction due to the fact that CRISPR can also be used to modify more cosmetic things, such as hair colour or height. This could lead to decreased diversity and further stigmatization of minority groups, especially while the technology is becoming more mainstream. Currently, there is no way to tell how accessible this tool will be — or what kind of price tag it could come with.

Beauclair agrees that all of these things are possibilities, but that doesn’t mean they can’t be well-managed.

“(The) argument then is that it leads to a slippery slope … (but) someone who declares that something is a slippery slope either lacks moral courage or is unable to make increasing refined moral distinctions,” Beauclair said. “There is a difference between eradicating cancer and offering someone the opportunity to change the pigment of their skin, and I think we can make an argument why that difference is significant.”

“I don’t feel that we have to approach this technology as an all-or-nothing thing. We don’t have to prohibit it absolutely, but that doesn’t mean we have to open the door wide open to all of its uses.”

Another dilemma surrounding CRISPR is the ability to create more effective gene drives. This is a way of forcing certain traits to be passed on genetically, and it has the ability to eradicate entire species from the ecosystem. Researchers have begun discussing whether mosquitoes should be eliminated to prevent the spread of diseases such as malaria. For many people, this thought causes anxiety because there is no way to know what domino effect mosquito elimination could potentially have.

Simpson defends this position, stating that the research has been sensationalized and misconstrued.

“They are only trying to reduce the instances of that malaria-carrying species in areas where malaria is a huge problem,” she said. “We’ve eradicated smallpox; we’re working really hard to eradicate polio. We, as a population, have allowed the eradication of certain entities from our world, and I think the idea of eradicating the malaria parasite would have a lot of support in the population.”

Regulations

There are currently no specific rules related to the CRISPR/Cas9 system, because while CRISPR makes the gene-editing process a lot easier, the discussion around embryonic cell research has been going on for a number of years. Though the restrictions vary for different countries, Canada has quite strict laws regarding how scientists can conduct research on a human embryo.

“The question is that now that we can make these changes in many, many different species, do the different areas like fisheries and agriculture need to look at their rules and reconsider them, because now you can do things in their species that they couldn’t do before,” Simpson said.

If science has shown us anything, it’s that it is constantly moving forward and reinventing what we thought was possible. Instead of fixating on potential negative outcomes, Beauclair emphasized that we should take a preemptive approach and work on our ability to adapt. He thinks that CRISPR has been a “model” for how other scientists should be going forward with their research, being open and transparent about what they are doing.

“Like anything, I don’t see why that can’t be regulated. We just have to find new safeguards. People find safeguards for being hacked on the computer, you know. You don’t stop the internet from developing just because there are hackers out there,” Beauclair said. “The role of the scientist ought to be what the role always has (been): you are producing knowledge for a public good.” 

Cover photo by Alley MacLean.