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The Swiss Army Knife of genetic manipulations!

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 to either cure a genetic disease or to design more productive plants or even to rewrite the genetic code of an elephant to recreate a mammoth from scratch. And that, simply and at a low cost!

Both researchers in 2015 received 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 can really take credit for. The researchers stumbled on CRISPR by chance while studying the genetic code of bacteria. So, it is a bacterium that could have received the award!

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

Later, in 2002, thanks to improved sequencing methods, Ruud Jansem of Utrecht University realized that the code of repeating segments observed by Ishino was in the DNA of many bacteria. He gave them a name: crispr, hence the acronym CRISPR. Only three years later, in 2005, scientists noticed something else, both strange and improbable. Eugene Koonin, an expert in evolution, hypothesized that CRISPR sequences were, in fact, a defence system against viruses. According to Koonin's hypothesis, bacteria use enzymes to absorb fragments of DNA fragments viruses. They absorb the fragments of the DNA of the virus in their CRISPR sequences. Later, when a new virus outbreak occurs, the bacteria use the CRISPR sequences to recognize and defeat the invading virus.

The hypothesis of Koonin was successfully validated in the dairy industry which uses bacteria extensively in its fermentation process during yogurt production. The CRISPR sequences are indeed a defence system, and the 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 in action within CRISPR sequences.

At the time, it was only to better understand the chemical mechanisms involved. What was originally 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 with a matching code. When appropriate, if another attack occurs, enzymes seize an RNA molecule with sequences stored in CRISPR, and go in search of a 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, the Doudna team soon realized that CRISPR could be a very effective genetic programming tool. Indeed, CRISPR was able to detect any DNA sequence and replace it with with a high level of accuracy. The history of this discovery took 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 allowed 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?



Sometimes we make a discovery by chance as it happened with the CRISPR discovery. But how can we provoke our luck? By testing and experimenting. Let's start now. Download your interactive guide and launch your first experiment.

For more inspiration, read the post The Game of Possibilities to see how the French Nobel Prize winner for Medicine, François Jacob, explains what governs us biologically and how it impacts our creativity.

And please, do not forget to let me know how your experiment went?


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