CRISPR in Aquaculture – Opinion Piece

Introduction:

This winter marks the beginning of my last semester here at Northeastern University. It’s been an exciting and unpredictable journey, but that’s a discussion for another article. I’ve sat down to write this opinion piece after my first few weeks of coursework. Specifically, my breathtaking dive into genomic editing with CRISPR and how this will inevitably reshape aquaculture.?

Given my distinct major and minor requirements, I’ve never had much of an opportunity to explore some of my school’s most fascinating biology electives. This semester marks my first and only semester with a course load I’ve had full control over. So, I signed up for Advanced Topics in Genome Editing and Stem Cells & Regeneration, courses that have quickly opened my eyes to the world we’re on the cusp of living in.?

Before CRISPR:

Much of today’s leading research relies on improving and utilizing CRISPR-Cas. Prior to CRISPR’s discovery and re-engineering, gene editing techniques were quite limited. You might be familiar with AquaBounty’s genetically engineered salmon. Almost 40 years ago, scientists introduced the impressive growth rate seen in Chinook salmon into the Atlantic salmon genome, resulting in an unprecedented growth rate in these fish. The technique used was transgenic insertion, and doing what AquaBounty did was no easy feat. Yet compared to what we can do with CRISPR today, transgenic insertions are simply incomparable.?

Decades ago, researchers engineered a process for inserting new genes directly into a cell’s pronuclei. Jargon aside, what became of this was truly groundbreaking, reaching far beyond salmon as transgenically-modified organisms today range from fish to plants to animals, and yes, even to humans. But generally speaking, it is difficult to use transgenes efficiently and accurately. There was often no telling where in the genome the transgene might end up – if at all – and how that would actually affect the organism. Most transgenic animals and crops today are the result of a tedious and expensive process of trial and error. However, transgenic modification is quickly becoming a thing of the past.

CRISPR:

CRISPR was first discovered in a bacterial genome in 1987, but its function and utilization was not uncovered until the 2010’s. The natural purpose of CRISPR in many bacteria functions much like an immune system. Bacteria with the CRISPR-Cas editing system are able to defend themselves against viruses known as bacteriophages, which hijack bacterial machinery to replicate themselves. When bacteriophages insert their own genetic information (typically in the form of DNA) into a bacterium’s cell, the CRISPR-Cas complex can identify it as foreign genetic information and cut it up in predetermined locations, rendering it useless. This precision “genetic slicing” as it were is known as cleaving or nicking, depending on whether one or both strands of DNA are cut.?

The precision and accuracy with which CRISPR-Cas complexes can cut DNA is key to its unfathomable application elsewhere. Unchecked, you can see how dangerous an enzyme that can destroy DNA might be. Thankfully, CRISPR-Cas complexes are highly precise, designed only to cut specific sequences found in the bacteriophage’s genome and not its own. This designed precision coupled with its incredible molecular accuracy is what researcher’s have been learning to exploit and improve upon these past years. And improve they have, since engineered CRISPR-Cas variants have recently been designed not only to make incisions at a given point in a genome, but to encode new information into the splice – in numerous organisms.

CRISPR in Aquaculture:

It’s hard to grasp the weight of this technology. CRISPR feels oddly xenobiological. Researchers have even found ways to fix faulty genes in humans. Yes, there are people living today thanks to CRISPR-engineered stem cells in their body. But let us regroup to discuss the application of CRISPR in aquaculture. That’s what I titled this opinion after all.?

Given the novelty and infancy of gene editing with CRISPR, current research on its application in aquaculture is limited. This is not to say it isn’t being done. Just last September, researchers at the Norwegian Institute of Marine Research published their findings on engineering sterile salmon, which, if applied, would render escapes much less ecologically harmful. But let me delve into some “what if’s” for a moment, considering this is all already or will soon be possible:

1. Nutrient uptake and expression. One of the greatest challenges in finfish aquaculture today is feed. Salmon feed, for instance, is typically meticulously designed from scores of ingredients in order to best mimic wild feeding habits and to produce the most nutritious filets for us. What if, however, salmon were less dependent on their specific nutrients for optimal health? Numerous finfish have significantly less intense dietary requirements than salmon. Combining a versatility enhancement of this nature with the concept of optimizing omega-3 absorption could result in healthier fish than we’ve ever seen, with feed costs – both environmental and financial – exponentially reduced.?
2. Hardiness and environmental adaptability. The world’s oceans, vast as they are, are largely inhospitable for many farmed fish throughout certain stages of their lives. There’s a reason Florida’s largest salmon farm is indoors. The fact that every inch of the ocean is teeming with life suggests that environmental adaptability comes down to genetics, as most things do. Salmon variants could be optimized for farming from pole to pole, from the deadly currents of the Southern ocean to the stillest inlets of the tropics.?
3. Kill switches. Sterile fish is a great step towards reducing and regulating aquaculture’s impact on the ocean’s ecosystems. If we are to continue down the path of designing our own animals, it would be important to install measures beyond intentional sterility. It would be entirely feasible with today’s CRISPR technology to remove a fish’s ability to create one of its many essential proteins. Herein you can see the “kill switch,” in that a farm could include the essential nutrient in its feed. Morbid? Perhaps, but preventing farmed fish from living more than a week beyond the cages of a farm would prove invaluable in the fight to protect natural ecosystems in the event of an escape.
4. Growth rate. Not a novel idea, no doubt about that, but the precision with which CRISPR allows genomic editing provides researchers with the ability to enhance growth rates like never before. Any unwanted side effects can be ruled out, and unlike modern growth-enhanced livestock, editing with CRISPR will allow there to be no downsides for the fish. Happy, healthy, and much larger finfish will soon turn eyes at grocery stores, I guarantee it.
5. Inshore and offshore farming of genetically modified fish. Compiling all of the augmentation I’ve listed above will mean nothing if these CRISPR fish can’t be farmed at scale. Luckily, the precision of CRISPR strikes yet again. Currently, no genetically engineered fish are farmed off land due to the great concern of unknowns. CRISPR eliminates these unknowns, and will actually provide us with more control than even wild fisheries can ensure. There will soon be no unknowns when it comes to CRISPR editing, beyond the random entropic mutations that all living cells incur naturally.?

Conclusion:

You can see that I’m quite excited about applied CRISPR technologies. If you stay up to date with my TikTok you’ve seen my deep-dives on the topic. And applications go far beyond the 5 I’ve listed. That is not to say I believe these genetic modifications should be brought about without due diligence. This will take time and there is more to consider than advancement alone. How will this impact/integrate with current aquaculture operations? In what capacity and how quickly will legislation come about that will allow for such novel and widespread applications of CRISPR? What is the best way to educate people so they do not fear the very technology that will, in some respect, save us all? These questions and more must be debated and answered in time. But for now, it’s exciting to consider how we might apply CRISPR technologies in what will soon become the Genetic Era.

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