The Nobel Prize in Chemistry 2020: The Cas9 scissors inside the CRISPR revolution

October 7, 2020 |

In Sweden, the Royal Swedish Academy of Sciences awarded the 2020 Nobel Prize in Chemistry to Emmanuelle Charpentier and Jennifer A. Doudna for their work on the smallest and most powerful scissors ever invented: the CRISPR/Cas9 genetic scissors. Digest readers will easily recognize Doudna for co-founding Caribou Life Sciences (more here) and also serving on the Scientific Advisory Board of Synthego (more here).

It’s more Cas9 than CRISPR, when you look at the Prize this year

They’ll say this is the CRISPR Award, that’s how it will be remembered. But it’s really the Cas9 award. The Nobel Committee decided to focus in on the discoverers and developers of the Cas9 enzyme, whose function is that it can cut DNA.

It’s poignant in some ways, this year of all years, because CRISPR is part of the system developed by ancient living things to fend off viruses, it’s a part of the ancient immune system. In ordinary nature, the Cas9 enzyme cuts the DNA of invaders, rendering them helpless.

The Academy wrote:

Using these, researchers can change the DNA of animals, plants and microorganisms with extremely high precision. This technology has had a revolutionary impact on the life sciences, is contributing to new cancer therapies and may make the dream of curing inherited diseases come true.

As so often in science, the discovery of these genetic scissors was unexpected. During Emmanuelle Charpentier’s studies of Streptococcus pyogenes, one of the bacteria that cause the most harm to humanity, she discovered a previously unknown molecule, tracrRNA. Her work showed that tracrRNA is part of bacteria’s ancient immune system, CRISPR/Cas, that disarms viruses by cleaving their DNA.

Charpentier published her discovery in 2011. The same year, she initiated a collaboration with Jennifer Doudna, an experienced biochemist with vast knowledge of RNA. Together, they succeeded in recreating the bacteria’s genetic scissors in a test tube and simplifying the scissors’ molecular components so they were easier to use.

In an epoch-making experiment, they then reprogrammed the genetic scissors. In their natural form, the scissors recognize DNA from viruses, but Charpentier and Doudna proved that they could be controlled so that they can cut any DNA molecule at a predetermined site. Where the DNA is cut it is then easy to rewrite the code of life.

The scientists will share the $1.126 million prize.

A Few Missed Out and Might Feel Modestly Overlooked

We called it “biotech’s biggest breakthrough” in 2016 when we profiled it here, and the applications keep on expanding in scope and utility. It’s been the work of many, why did the Nobel Committee focus on these two?

Others could have been in the mix. For instance, Francisco Mojica who discovered and named the repetitive DNA sequences known as CRISPR. When they handed out the Kavli Prize in Nanoscience, they added Virginijus Šikšnys along with Doudna and Charpentier for his work in the Cas9 instruction set, part of what makes it so useful. The 2017 Albany Medical Center medicine prize included the Nobel laureates, and MIT/Harvard’s Feng Zhang, who developed key modifications to the system. Harvard’s George Church defined methods to bring CRISPR-0Ca9 into the mammalian cell system. Utah’s Dana Carroll developed zinc-finger nucleases for genome editing even before CRISPR-Cas9 came along.

In the end, the Nobel Committee focused on the discovery rather than the key modifications and improvements. In their own way, the Committee found their own scissors to cleave away the modifications and the underlying discoveries and hone in on the key breakthrough.

Reaction from the Stakeholders

“There is enormous power in this genetic tool, which affects us all. It has not only revolutionized basic science, but also resulted in innovative crops and will lead to ground-breaking new medical treatments,” says Claes Gustafsson, chair of the Nobel Committee for Chemistry.

Since Charpentier and Doudna discovered the CRISPR/Cas9 genetic scissors in 2012 their use has exploded. This tool has contributed to many important discoveries in basic research, and plant researchers have been able to develop crops that withstand mould, pests and drought. In medicine, clinical trials of new cancer therapies are underway, and the dream of being able to cure inherited diseases is about to come true. These genetic scissors have taken the life sciences into a new epoch and, in many ways, are bringing the greatest benefit to humankind

Doudna told Nature earlier today, “I’m really stunned, I’m just completely in shock. I know so many wonderful scientists who will never receive this, for reasons that have nothing to do with the fact that they are wonderful scientists. I am really kind of humbled.”

More on the story.

The Bottom Line

Let’s consider this perhaps the confirmation that we have entered into a new era, one of engineered biology.

For some time we’ve struggled for a term to describe what is going on. I have long disliked the term synthetic biology, because as a metaphor is conveys something that is an alternative to nature, which is to day, not natural. The idea that this field is not natural — that it creates frankenfoods and microbial monsters more to be feared than used — has led the the worldwide disdain for the term “GMO” or genetically modified organisms.

What has been going on is the engineering of a toolkit — using nature, not replacing it. Scientists did not invent the Cas9 enzyme or the CRISPR pattern found in the genetic code of most life forms. Any more than scientists invented carbon and iron they used to make steel and fashion that steel into a hammer. What scientists have done is to discover the enzyme and the DNA sequence and to understand the significance of the discovery — that it had the potential to be applied more widely and more precisely, in the search for solutions to an array of human problems.

At some stage in the distant past, someone saw something unique about fire — it wasn’t just a phenomenon, it was a tool for cooking, for transformation of materials, for heat and safety. Fire was tamed through engineering. Sure, we see fire in the California hills and feel the ancient terror that we share with all animals — we haven’t fully tamed fire, thousands of years on, vigilance is required. But our fear of consequences has not blinded us to the advantages of taming fire, and tamed it to a great extent we have. Some of the electrons being used to power the reading of this page come from that.

And so it will be with editing of the code of life itself.

Tools, tools, tools. We are makers of them, that is our destiny. But fear not, these are good tools, and it is a great discovery that was made. Lucky us to live in such times, and to work amongst these pioneers. Around the world today, countless post-docs and professors and government researchers and private sector R&D and company leaders and colleagues are probably thinking back to the first day they heard of CRSIPR and all the advances made by these Nobelists and others since then.

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