The westward expansion of the United States in the second half of the 19th century is often quoted as the quintessential ¡°¡±. In a romanticised illustration of this process, hardy individuals and tight-knit groups set out to reclaim the Wild West from nature, red in tooth and claw. And while one can argue about issues of justice or forcible displacement of native populations, one point remains irrefutably true: life on the frontier was drastically different from life in settled regions.

Science, characterised if not by a linear progress then certainly by some form of expansion, also comprises frontiers and core regions. This might seem paradoxical, as we axiomatically view every scientific endeavor to be located on some frontier. Yet the differences between true frontiers and war zones could not be more stark.

When in Jennifer Doudna and Emmanuelle Charpentier discovered the potential of the gene editing platform Crispr, it was a frontier ¨C wild, largely unexplored and full of potential riches. And, similar to the discovery of gold on 16 August? in the Klondike in northwest Canada, it immediately sparked a rush of research frontiersmen and women to the field of gene editing.

In the following years, Crispr was used for gene editing as well as countless other creative applications including and gene expression. But what happens to frontiers after they are populated and settled?

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During the westward march across the US, Kansas was inducted into the union in January . This event was preceded by seven years of bloody warfare between pro- and anti-slavery groups to decide whether Kansas would enter the US as a free state or a slave state. As a frontier, the people inhabiting the lands to be known as Kansas largely fought nature. But as a figurative and literal war zone, people fought people; sustenance and survival transitioned to a drive for power and ever increasing organisation.

A mere three months after entering the union, Kansas found itself in yet another conflict: the American Civil War.

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Crispr was a frontier, but it is now a war zone. Back in 2012, it had just been wrested from nature, wrought into a form usable by a great number of scientists.?In 2019, it is now a mass commodity in the academic realm. Competition between research groups is incredibly intense, both to further improve Crispr-based techniques as well as to apply them.

That is what war zones are like: pitched battles lead to lightning-fast turnarounds, with new results whenever you hit refresh on the academic literature. Frantic fighting is so intense that there is no time to think, no time to pause and reflect because then someone else will be faster than you. On the frontier, any victory can be considered an advancement for humanity, but in war zones ever detail during and after the battle counts. Kansas entered the union as a free state, at least in part because anti-slavery forces prevailed, and it remained a haven of staunch loyalty to the North during the entire Civil War.

The main reason why there is so little conflict and competition between people on the frontier is simply that there are no people. during the American expansion defined a frontier as a region with roughly one inhabitant per square kilometre on average. Just for context, the city of had a density of 5,538 citizens per square kilometre in 2018.

Exploring and reclaiming frontiers is lonely and can take years or even decades. Because it is such a glacial process, nobody pays attention to single actions until the wilderness starts to be tamed. Frontiering is also daunting as there is no infrastructure; you have to be creative and make things up as you go along. It comes with little surprise that most frontier endeavours end in failure. For every Crispr gold rush, countless other explorations into the truly unknown peter out.

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Most people will not understand why you would want to settle this rough landscape in the first place. Why not try to crossbreed a slightly better apple variety instead of venturing into the icy, subarctic Yukon?

This places a huge responsibility upon the expedition leader, who may doom their fellow explorers (or at least their careers) by potentially leading them on a wild goose chase. While both war zones and frontiers require substantial funds, it can be inordinately more difficult to convince organisations to fund your venture into the unknown.

It is also a challenge to attract the best talent to your team of adventurers. Before you hit gold, nobody sees value in your chosen destination. And, maybe even worse, afterwards everyone does. Studying an obscure bacterial endonuclease like Crispr-Cas9 prior to 2012 did not bring you fame or riches. It would seem that most people transition to war zones in search of glory, attracted by the sheer scale of events that are unfolding ¨C because it is just so obvious that fighting for the abolition of slavery in Kansas is important, both to fighters as well as funders.

Frontiers are no less intrinsically rewarding, with the allure of the unknown, but they also hold the temptation of the untrodden path; and they are home to potential untold riches. As Ralph Waldo Emerson said, ¡°The creation of a thousand forests is in one acorn.¡± So be creative, be crazy, be obstinate. Set out to conquer new frontiers. Who knows, while everyone else is busy fighting battles, you might stumble upon the next Klondike.

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Daniel Bojar is a postdoctoral researcher at the??for Biologically Inspired Engineering at Harvard University.