CRISPR

The discovery of the century!

This technique—discovered in 2013 by the team of biochemists, Jennifer Doudna of Berkeley University and Emmanuelle Charpentier of the Centre for Research on Infectious Diseases Helmholtz in Germany allows scientists worldwide to modify the DNA of any living organism in order either to cure a genetic disease or to design more productive plants or even to rewrite the genetic code of an elephant to recreate from scratch a mammoth. And that, simply and at low cost!

Both researchers received, in 2015, The Breakthrough Prize, sponsored, among others, by Mark Zuckerberg, rewarding a revolutionary discovery in various technological fields. One of the most amazing features of this discovery is that no one has really invented it. The researchers felt by chance on CRISPR while studying the genetic code of bacteria. It is a bacterium that might have had the award!

CRISPR: 
the Swiss Army Knife of genetic manipulations!

Drawing: Pierre Guité. CRISPR, The discovery of the century by Sylvie Gendreau, Pocket Lab, DreamingTheWorld.tv

Drawing: Pierre Guité. CRISPR, The discovery of the century by Sylvie Gendreau, Pocket Lab, DreamingTheWorld.tv

The history goes back more than 25 years. It owes its success to chance and curiosity. The first who spotted the existence of CRIPSR did not understand what it was. In 1987, Yoshizumi Ishino of Osaka University has accidentally spotted in the DNA of a bacterium's presence "sandwiches" made of strange repetitive code segments. He published the results of his observations without understanding their meaning.

Later, in 2002, thanks to the sequencing methods that have improved meanwhile, Ruud Jansem of Utrecht University realized that the code of repeating segments observed by Ishino were in the DNA of many bacteria. He gave them a name: crispr, hence the acronym CRISPR. Only three years later, in 2005, scientists noticed another thing both strange and improbable, for CRISPR sequences: they looked at the genetic code of the virus. Eugene Koonin, an expert on evolution, then let out a hypothesis: the CRISPR sequences were in fact a defense system against viruses. According to the hypothesis of Koonin, bacteria uses enzymes to absorb DNA fragments viruses. They insert the fragments of the DNA of the virus in their CRISPR sequence. Later, when a new virus outbreak occurs, the bacteria uses the sequences stored in CRISPR to recognize the invading virus and delete it.

The hypothesis of Koonin was successfully validated in the dairy industry. The dairy industry uses bacteria extensively in its fermentation process for yogurt production. The CRISPR sequences is indeed a defense system. And bacteria used were becoming resistant to viral attacks. In 2007, Blake Wiedenheft, a postdoc, joined the Jennifer Doudna team. The objective of the research project was to study the structure of enzymes into action within CRISPR sequences.

At the time, it was only to better understand the chemical mechanisms involved. What originally was a banal research project motivated foremost by curiosity proved to be much more interesting. What are the mechanisms involved when a virus outbreak occurs in a bacterium? At the time of the attack, the bacterium seized a portion of the DNA of the virus. It stores well and is the showcase of all potential enemies which it may face. Enzymes that work with CRISPR can then refer to the blacklist to accurately target every virus whose code matches. When appropriate, if another attack occurs, enzymes seize a RNA molecule with sequences stored in CRISPR, they go in search of the virus with the corresponding sequences.

When the enzymes eventually identify the virus in question, the RNA binds to the viral DNA and the enzymes cut the DNA of the virus in order to prevent any possibility of reproduction. In 2013, Doudna team soon realized that CRISPR could be a very effective genetic programming tool. Indeed, CRISPR was able to detect any DNA sequence and to replace it with another with high accuracy. The history of this discovery takes place over a period of about 25 years.

Many researchers around the world participated. It happened thanks to the sustained curiosity of these researchers and their freedom of action that allow them to conduct projects which were justified only by a desire to know and understand, and, of course, the inventiveness of life: Who would have imagined that a simple bacterium was capable of such creativity?


Sources:
Doudna, Jennifer. Genome Gambits. MIT Technology Review, Vol 118, No 3.
Zimmer, Carl. Breakthrough DNA Editor Borne of Bacteria. Quanta Magazine, February 6, 2015.