The discovery of CRISPR and its exploitation to edit/manipulate genomes is revolutionizing biology. If you haven’t heard of CRISPR, see the video below.

We can extract some important lessons from the history of how CRISPR was discovered and technology exploiting it was developed. I passionately believe that the story of this scientific advance epitomizes how science realistically progresses. Although I am a young scientist, the story aligns with my own experiences as well. As this story of scientific advance has important implications for how we fund science, it is important to disseminate it.

The full article in Cell is here. I want to highlight a few points here.

• Contrarty to the stereotype that scientists are lone wolfs working solo in a lab, the discovery of CRISPR, its significance, and its exploitation to manipulate genomes was a gradual, building process with many different groups involved.

Finally, the narrative underscores that scientific breakthroughs are rarely eureka moments. They are typically ensemble acts, played out over a decade or more, in which the cast becomes part of something greater than what any one of them could do alone. Eric S. Lander. “The Heroes of CRISPR.” Cell (2016) DOI

• When CRISPR was first discovered, these scientists did not set out to find a way to manipulate genomes and cure disease. Instead, they were curious about microbes that could survive in salty water. Many policy-makers criticize research funds that go into basic, curiosity-driven research as wasteful compared to applied research, but this story of CRISPR epitomizes that imporant discoveries often come about from basic research that, at first, has very little to do with a direct application.

The most important is that medical breakthroughs often emerge from completely unpredictable origins. The early heroes of CRISPR were not on a quest to edit the human genome—or even to study human disease. Their motivations were a mix of personal curiosity (to understand bizarre repeat sequences in salt-tolerant microbes), military exigency (to defend against biological warfare), and industrial application (to improve yogurt production). Eric S. Lander. “The Heroes of CRISPR.” Cell (2016) DOI

• A critical breakthrough in discovering the significance of CRISPR came about when a scientist found certain DNA sequences associated with CRISPR. He then searched a database to find that these DNA sequences matched that of certain viruses, leading to the discovery that “CRISPR loci must encode the instructions for an adaptive immune system that protected microbes against specific infections”. The point is that this database of DNA sequences was built as a platform to advance science. Storing this data in one place and making it widely available to researchers can lead to advances and discoveries that were not specifically envisioned when such a database is initiated, which Lander calls “hypothesis-free” science:

The history also illustrates the growing role in biology of “hypothesis-free” discovery based on big data. The discovery of the CRISPR loci, their biological function, and the tracrRNA all emerged not from wet-bench experiments but from open-ended bioinformatic exploration of large-scale, often public, genomic datasets. “Hypothesis-driven” science of course remains essential, but the 21st century will see an increasing partnership between these two approaches. Eric S. Lander. “The Heroes of CRISPR.” Cell (2016) DOI

• Finally, it is interesting to note that some of the seminal papers on CRISPR were rejected from the leading scientific journals; one of the seminal papers took a year to get published.

Their seminal papers were often rejected by leading journals—appearing only after considerable delay and in less prominent venues. These observations may not be a coincidence: the settings may have afforded greater freedom to pursue less trendy topics but less support about how to overcome skepticism by journals and reviewers. Eric S. Lander. “The Heroes of CRISPR.” Cell (2016) DOI

UPDATE

As Michael Eisen pointed out in his blog post, “The Heroes of CRISPR” article was written with a conflict of interest and may not be the most impartial story of how CRISPR was discovered. That said, the points I made here still hold!

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