THE NEED FOR SPEED IN PLANT BREEDING

A changing climate. Limited arable land. Increasing pest resistance: How speed can help us overcome current sustainability challenges in the new millennium.

For hundreds of years, North America’s farmers have felt they could safely assume that next year’s weather would be much like last year’s and every other year’s, with adjustments for predictable cycles. That’s no longer the case. True, there have always been extreme weather events such as droughts and floods, but for the most part, they were rare. One of the hallmarks of the new millennium is that changes seem to be more severe and happening more frequently, even in what were assumed to be immutable natural cycles. This creates a huge problem for agriculture, which traditionally has taken many years (if not decades) to develop new crops or protective traits that might be bred into crops.

In the nick of time, a new biotechnology — precision gene editing — has emerged that can help farmers adapt to change as it happens.

Current Farming Threats

The need for precision gene editing is undeniable. Climate, for instance, is changing at a faster pace today than at any time since human civilization began, and that confronts farmers with a welter of challenges. Hundred-year floods, droughts and heat waves have become common events; storms have become more violent; downpours more intense; and growing seasons have shifted. Farmers also must contend with the second-order impacts of these changes. One of the postulates of evolutionary biology is that in unstable environments, rapidly reproducing species (such as microbes, fungi and insects) have the advantage. For farmers, this means that whipsawing weather also forces them to deal with more frequent outbreaks of pests. One extreme example? The plagues of locusts — so big they can be tracked by satellite — now devouring crops in Africa, India and the Middle East.

For temperate farmers, a major threat comes from resurgent blights. With both traditional plant breeding or GMO technologies developed in the nineties, it takes upwards of 14 years to breed a plant resistant to a new blight — if it can be done at all. Faced with such waits combined with the need to ensure food safety and production, farmers turn to increased use of fungicides and other external treatments, with their additional expense and environmental concerns.

But precision gene editing can help alleviate some of the current threats brought on by climate change and increased fungicide resistance. For example, specific applications of precision gene editing can enable us to breed a resistant plant in as little as one-tenth the time of either traditional plant breeding or GMO technologies.

The Precision Gene Editing Solution

The order of magnitude acceleration that precision gene editing offers comes from structural advantages, as well as from increases in efficiency from optimizing and automating the processes involved — arising from years of experience working with these technologies.

The structural advantages are obvious. For instance, with GMO or transgenic technologies, the discovery phase — the phase during which a desired trait is identified — typically takes four to five years. That is because, with transgenics, biochemists have to develop and then test thousands of transgenic events before selecting a few synthetic gene insertions to advance and put into a crop, a process that takes an additional two years.

None of these steps are necessary with precision gene editing, since the technology works with the native genes within an existing crop. Instead, we sequence the genome of a crop — a process that takes 10–14 days. Nature has equipped plants with tools to repair errors introduced into the genome resulting from assaults a plant experiences each day (such as from the sun’s radiation). We use these innate tools to target desired edits. Once we have the gene sequence, it takes a few months to determine the precise edits to enable a desired trait, confirm their location within the genome, develop and validate the editing tools, including the oligonucleotide — the chemical construct that will stimulate the gene’s own repair mechanisms to make the desired edits. Customizing the “oligo” to specify the desired edits is the product of computation and bioinformatics, but not lab work. Like a computer chip, the oligo is made by a machine. But unlike a computer chip, the oligo is entirely dissolved and eliminated as soon as its job is done.

Similarly, because this specific application of precision gene editing works entirely within a genome, the technology has a structural advantage with regard to speed at the other end of the process. Because traits produced by precision gene editing are indistinguishable from those produced in nature, most of the world is treating these traits as equivalent to random mutagenesis and traditional breeding, as has been done for decades with an exemplary history for safe use. By contrast, crops with foreign DNA inserted undergo regulatory scrutiny that can take years.

Precision gene editing also has a structural advantage in the breeding of the trait itself. Many yield-enhancing traits require edits at several different places in the genome. Using our oligo, we can make these edits simultaneously. In the past, GMO technologies have struggled to make these changes in series, a process that can take many years, depending on the number of locations. Traditional plant breeding might take forever if several genetic changes are required (if possible, at all).

Decades of Mastering the Craft

Apart from structural advantages, twenty years of experience working with the various aspects of gene editing have allowed us to optimize and automate steps on the path from identifying a problem to producing a solution. Improvements in efficiency and lowered costs translate into improvements in speed. Cost savings improve speed because lowered costs allow us to repeat operations without worrying about incurring prohibitive expenses.

Here are some examples of the improvements coming from optimization and automation:

In the Discovery Phase:

• The cost of sequencing has dropped by two-thirds over 20 years, even as the quality improved. Lower costs make sequencing a routine decision; richer information allows us to know not just what the genetic targets are, but where they are located.
• Results: The process of identifying targets and determining where they are has shortened from years to in some cases weeks.

In the Editing Phase:

• Once we introduce the oligo into a pool of plant genes, those cells with desired edits must be identified — essentially, we’re looking for needles in a haystack. Over the past 10 years, we have reduced the size of the haystack and improved the odds of obtaining cells with our desired edits.
• Results: This phase now take 1/50th the time it did a decade ago.

Growing Cells into Plants:

• Where in the past highly qualified scientists had to look for converted cells, robots now screen for such edits, and our robots are four times faster than humans and can be scaled to identify edits across all our crops.
• Results: Finding and moving edited cells into a growth medium and then nurturing the plant embryos has sped up by a factor of 200 over the past 10 years, and also freed up our highly qualified scientists to focus on innovation — not drudge work.

General Improvements:

The creation of trait platforms, essentially assembly lines for the editing process. Once a platform has been developed, it can be adapted to solve different problems.

“Cross-crop experience.” By solving problems for trait development for a given crop such as canola or rice, that expertise enables the development of traits in other crops.

• Expertise gained in developing resistance to one fungus afflicting canola has given us a leg up in understanding how similar fungi challenge other crops.
• Understanding how a disease impacts a plant can speed understanding of other environmental challenges. For instance, breeding potatoes with the ability to resist late blight (Phytophthora) may enable tubers to better survive droughts.

Finally, increased speed drastically lowers the cost of new trait development, meaning that breeders can attempt to help farmers create more robust crops that might have been previously ignored by the big agricultural technologies prohibitive expense made for a low return on investment. There are many problems that can be addressed if the total cost is $10 million that would not be considered if breeders faced a budget of $130 million and 10–13 years of commitment. Similarly, there are many more companies that can spend $10 million to tackle an emerging threat to the food system than there are companies prepared to spend ten times that amount.

Precision gene editing promises to revolutionize plant breeding, opening the field to new players, enabling solutions for problems that have eluded plant breeders either because of expense, complexity or size of the crop and, most importantly, vastly speeding up plant breeders’ response to the new challenges of the new millennium.