Fundamentally Newsworthy

The all-consuming news story in biology this year—this decade really—is the discovery of the CRISPR/Cas9 system and its practical application for gene editing. At least three other essays in this book mention or refer to this new technology; there have been numerous articles in the popular press. Most of that attention has been directed at the tremendous and potentially dangerous power of this new technology: it allows "editing" the DNA of genomes, including those of humans, in a way that would be permanent—that is heritable through generations.

All this attention on the possible uses and misuses of CRISPR/Cas9 has obscured the real news—which is, in a way, old news. CRISPR/Cas9 is the fruit of years of fundamental research conducted by a few dedicated researchers who were interested in the arcane field of bacterial immunity. Not immunity to bacteria as you might at first think, but how bacteria protect themselves against attack by viruses. Weird as it may seem, there are viruses that specialize in attacking bacteria. Just as most viruses we know about are specific to one species or another—you can’t catch a cold from your dog—there are viruses that only infect bacteria, in fact only certain types of bacteria. These have a special name—phage. And they have a long history in the development of molecular biology and genetics. Indeed molecular biology began with the study of phage and its ability to insert its genome into the genome of bacteria—even before Watson and Crick’s famous articulation of DNA as the molecule of heredity.

For the past forty years restriction enzymes, another family of bacterial proteins, have been the mainstay of the biotech industry, and they too were discovered first as an early example of bacterial mechanisms to protect themselves against invading viruses. And they were also discovered in university research laboratories devoted to fundamental basic research. CRISPR/Cas9 however is a more sophisticated mechanism, approaching that of the immune system of higher animals: it is adaptive, in the sense that a bacterium and the other bacteria it generates by dividing can "learn" and destroy the DNA of the genome of a particular type of phage after it has been attacked by that phage once. The researchers who discovered CRISPR/-Cas9 and recognized its potential value as a gene editing tool in living things other than bacteria were not searching for some new technology, they were after a deeper understanding of a fundamental question in prokaryotic (microbial) biology and evolution—the back and forth competition between bacteria and the viruses that invade them. Could that be any more arcane sounding?

It is also important to recognize that this was not a serendipitous discovery, a happy accident along the way. This is often the case made for supporting fundamental research—that you never know where it might lead, serendipity intervenes so often. But this is a false conception and CRISPR/Cas9 is a perfect example of why. This was no simple accident resulting from good luck or happenstance. It was the fruit of hard and sustained labor, of whole careers devoted to understanding the fundamental principles of life. Work in this area goes back thirty years, and the particular groups that discovered CRISPR/Cas9 were looking for precisely such an adaptive, immune-like response in bacteria. Understanding the value of restriction enzymes, as these researchers would have, was a sensible leap to appreciating the value of a potentially even more sophisticated DNA-based protective system. This is how research works—neither by accident nor by purpose—it is the result of hard work at every level of inquiry. Indeed advances are often unpredictable, but that doesn’t make them merely lucky. Certainly not like winning some type of lottery.

We continue to have this misguided debate about fundamental versus applied research as if they were two spigots that can be operated independently. They are one pipeline, and our job is to keep it flowing. This is old news, but we should never tire of saying it. And in this case it created the biggest news in biology in a decade—CRISPR/Cas-9.