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Building Better Blueprints, One Gene at a Time
Ever since its introduction to the world a decade ago, a genome-editing tool called CRISPR-Cas9 has become one of the most talked about scientific breakthroughs. And while it has generated a lot of buzz - and was even awarded the Nobel Prize for Chemistry in 2020 - CRISPR is just one of the genome-editing tools being used to drive incredible advancements across the life sciences, including agriculture.
The Potential of Genome Editing for Agriculture
It fills me with tremendous optimism to see with increasing frequency new articles and research papers about the potential scientific breakthroughs of genome editing. What draws me to these pieces is the great promise that this innovation holds for researchers to solve previously unsolvable problems, like treating incurable and fatal genetic diseases, modifying human immune cells to kill cancer cells, and even curbing the spread of Malaria, which still kills 627,000 people each year. In agriculture too, we are expanding our understanding as to how genome-editing could help tackle the critical agronomic and sustainability challenges we face. Today plant scientists are using the technology to design plant varieties for better yields, improved resilience to extreme weather conditions, increased resistance to diseases and pests, reduced need for fertilizer or boosted nutritional value, to name just a few examples. All of these innovations would be a win for both people and the planet.
Yet despite this promise, the successful application of genome editing hinges on its acceptance by society. As the world urgently seeks new ways to ensure the supply of safe, healthy and affordable food – made more precarious by the COVID-19 pandemic, the war in Ukraine and the effects of climate change – I am encouraged by the increased interest in the potential of genome-editing for agriculture. However, it also concerns me that the scientific community still isn’t doing enough to help the public understand exactly what this technology does, why it’s something to celebrate instead of fear, and why scientists, like me, are so excited about it.
This article is my attempt to do that.
CRISPR is often described as a pair of molecular “scissors” that enable scientists to make precise changes to a strand of DNA, which is often referred to as the “Blueprint of Life”. Other genome-editing tools are said to function more like a “pencil and eraser.” So, using these familiar terms – scissors, pencils, erasers, and blueprints – here’s a story that hopefully helps bring these concepts together in a more concrete way.
That Time I Built a House…
When I was in my early twenties, I built a house. And I don’t mean that I hired a contractor to build a house, or picked out a floorplan in a new neighborhood development – I mean that I literally drew the blueprints and, with the help of two family members, built the entire house from the ground up.
This is where I should probably remind you that I’m a plant scientist, not a carpenter or construction worker. The biggest thing I’d “constructed” before the house was probably my sixth-grade science fair project when I built a detailed model of the entire cellular respiratory pathway using only my sister’s college biology textbook as a reference.
Fast forward about ten years to when I won a government lottery for one of a few properties at a new lakeside development in Manitoba, Canada, where I’m originally from. I only had to pay $350 for the land—so taking it was a no-brainer, but the catch was that I had to build a house on it within five years.
I was still in graduate school at the time—needless to say, I couldn’t afford to hire professionals to build the house for me. So, I did what any other financially-challenged, but technically-minded college student would do: I went to the University of Wisconsin library, studied all the construction books I could find in the engineering section, drew the architectural plans for my house, and miraculously, got them approved.
Then, over the course of a few summers, my dad, brother-in-law and I brought this dream to reality. Our construction process was slow but precise. I was the reader and translator of the blueprints, cutting each board or tile to the correct measurements. Then I gave detailed instructions to my “crew,” telling them exactly where each piece needed to go. And eventually, we ended up with a pretty impressive 1,400-square-foot lake cottage that my family still uses to this day.
Everything hinges on the blueprint
Over the years I’ve thought back on that process many times and especially when observing the advances in human health and agricultural research thanks to our increasing knowledge about DNA and genetic sequencing.
Much like the blueprints that informed the building of my house, DNA provides the information for building all the proteins within every living thing on Earth—humans, animals, plants, bacteria, and other single-celled organisms. Proteins are like the building blocks of our bodies. Everything we do is controlled by the proteins within our cells, and each gene in our DNA contains the code for a unique protein structure.
DNA can’t do it all alone; it relies on molecules called Messenger RNA (mRNA) to deliver the instructions for building each protein to the parts of the cells that make them. In my house-building analogy, I was like the Messenger RNA, reading the blueprints and delivering specific instructions for building each piece of the house (or protein) to my crew, which then carried out the orders.
Now consider this: what if there was a defect in the blueprint for the house? If we followed those instructions anyway, the defect would be built into the house—which could later lead to structural problems, ranging from minor to catastrophic, depending on which part the defect involved.
But – if I was able to pinpoint the defect in the blueprint, I could take an eraser and pencil to fix the mistake (or use scissors to snip out the faulty section and replace it), then deliver those new instructions, and my crew would build the flawless version of the house.
On the other hand, if I wanted to add a feature to improve the house design mid-construction, like adding a window or moving a wall, I could do the same thing: update the blueprints and deliver the improved instructions to the building crew. It’s important to remember that, relative to the size and complexity of the blueprint, these changes are small and precise. The house as a whole will still stand as it would have before, with one or two targeted improvements having been made.
This “fine-tuning” is what genome-editing tools are now enabling scientists to do; to develop plants with improved characteristics faster, more precisely and efficiently than ever before. And helping farmers to grow better crops to meet the needs of a growing world while reducing the environmental burden of agriculture is, I believe, certainly worth getting excited about.
Genome editing vs. genetically modified organisms (GMOs)
Genome editing does not introduce DNA from a different species (unlike genetically modified organisms or GMOs which transfer a desirable trait from one species to another). Changes brought about through genome editing are therefore comparable to those that might occur through natural selection or through selective breeding. Therefore, regulators in much of the Americas, Australia, Japan and India have either defined genome editing to be exempt from GMO regulations or are evaluating product candidates on a case-by-case basis—a rational, science-based approach that I agree with. Keep in mind that all new plant varieties still go through years of field trialing and safety testing before they are made available to farmers to grow.
Often, I am asked if genome-edited seed products will replace the GMO seeds available to farmers today. Here I go back to my construction story and consider building my house in a warmer climate. In a “genome-editing scenario,” I could edit the blueprint and redraw the structure to have thicker walls, more insulation, and properly positioned windows to mitigate the effects of high air temperatures and help keep the house comfortable on hot days. But if I really wanted the house to be cooler, I would need to “genetically modify” the blueprint to include an air-conditioning unit—an external “trait” not included in the home’s original design. So sometimes there are limits as to what we can do to improve a plant by just editing its native DNA sequence, and I foresee a continued need for both types of technology to meet the world’s agricultural challenges.
Designing a house in the digital age
If I won the same lottery today as all those years ago, chances are that I would not be spending hours in a library pouring over books and drawing up the plans for my future house, as I did back then. Instead, I would fire up my computer and use special software to design it based on my pre-requisites. Artificial Intelligence would offer enhancements to my idea of a perfect house using insights and predictions about the land, positioning and surroundings to propose the best possible blueprint in terms of efficiency, safety and sustainability, for example.
As the work of an architect has evolved with the advent of digital tools, so too has the work of the agricultural scientist. By bringing together an increased understanding of genetics, experience in plant breeding and the power of data science, crops with improved characteristics can be ‘designed’ by means of computer modelling or simulation – just as a house can be. Seeds can then be created using a state-of-the-art genome editing toolbox that writes and assembles the specific genomic architecture for the improved crops.
This approach creates the potential to build completely novel traits across a wide variety of crops which will allow us to both accelerate and expand the range of solutions and alleviate the global pressures that are putting both food security and the future of our planet at risk.
Communicating the benefits of a better blueprint
Scientific breakthroughs like genome editing are the reason I became a scientist—I’ve always been motivated to do research that helps make the world a better place. The safe and responsible use of these tools can do just that. However, it will take increased understanding of genome-editing tools and the products they enable for the technology to be fully accepted and applied across industries and around the world. The only way that will happen is if those of us who have already embraced genome editing can do a better job of communicating with those who haven’t. We must help people understand that genome editing works with nature in a way that is safe ... and that a better blueprint builds a better house.