Emmanuelle Charpentier

A French biologist invents the absolute weapon to correct, improve or reedit life

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She hasn't yet received the Nobel Prize in Chemistry but today she won the Princess of Asturias Prize. Emmanuelle Charpentier, an outstanding microbiologist, developed in 2012 a technique with the sweet name CRISPR/Cas. This technique will continue to revolutionize the engineering of living organisms. This molecular surgery opens up dizzying possibilities. With their procession of ethical and regulatory emergencies.
 
E...he traded dancing for the exploration of bacterial defences. Emmanuelle Charpentier embodies strength of character and curiosity. This French biologist, born in 1968 in Juvisy (Essonne), has just been awarded the Princess of Asturias prize, the most prestigious prize awarded in Spain. For the past six years, she has given a series of lectures and distinctions: in April 2015 she received the Louis-Jeantet Prize for Medicine in Geneva); we also remember the ceremony of the Breakthrough Prize in Life Sciences, California, in November 2014, where she received with his collaborator Jennifer Doudna, from Berkeley....a price tag of nearly $3 million.
 
A prodigious molecular cooking tool
 
Why so many accolades? Emmanuelle Charpentier's work has led to a real revolution in the world of design of living organisms. If since 1975, genomes have been manipulated by grafting pieces of information onto them to make new productions (insecticides, herbicides, drugs...) no one had yet managed to target and add genes just where they were needed. The invention of Emmanuelle Charpentier and her American colleague Jennifer Doudna (University of Berkeley) consists of using an ultra-precise "seeker head" capable of locating and destroying an insertion zone in the genome. Their discovery is an illustration of serendipity since the scope of the tool was never imagined by the two researchers at the outset. The hazards of the desire to understand...
 
It all started with Emmanuelle Charpentier's interest in the immune system of ... bacteria. Yes, microbes have memories! They learn to repel the viruses that infect them by multiplying countless copies of the little bits of viral DNA. These repetitions are like stuttering, spotted as early as 1987 by Philippe Horvath's Charente team working for the Danisco company (bought out by Dupont). This trace, thus fixed, proves to protect the bacterial strains from future attacks by the virus.
 

Jennifer Doudna presenting CRISPR - Case9
 
We still had to understand the mechanism of this resistance. The two researchers Charpentier and Doudna published their decisive work in 2012 (1). They show that the bacterium has a real sentinel system which, as soon as the DNA of the virus already recognized penetrates the bacterium to take control of it, the latter locates it thanks to its system called CRISPR (Clustered Regularly Insterspaced Palindromic Repeats) and cuts it off by its "homing head enzyme" called "Cas9". The potential of the technique as a tool of genetic engineering was highlighted in the following months with the publication of Luciano Maraffini of the Rockefeller University in New York (2).
 
Precise, efficient, simple and ultra fast
 
From then on, it is the explosion of the CRISPR/Case technique that proves to be precise, efficient, simple and ultra fast. With it, everything becomes interchangeable: Feng Zhand of the Broad Institute of MIT in Cambridge describes CRISPR/case as the "search and replace" function of a computer. The tool is also universal: it can be used to improve wheat or potato seeds, add traits to livestock species, correct genes in human embryos.
 
 
 
The power of the method works "wonders" as the journalist of Le Monde, Stéphane Foucard, points out in his article Editing nature. Chinese researchers have succeeded in making wheat resistant to powdery mildew by inactivating all six copies of the fungus receptor gene. Lisong Li of the University of Shanghai corrected an inherited mutation responsible for cataract in mice. And last April, the team led by Junjiu Huang of Sun Yat-sen University (Canton) - still Chinese - published in the journal Proteins and CellsThe work to modify human embryos. The stated goal is to correct a gene responsible for a blood disorder: the beta-thalassemia. Undeclared target: get a head start in the race for a new EldoradoThe first is the issue of transmissible genetic modifications in the human species.
Now that the Chinese can genetically modify humans, why don't we press "pause" to think about it for a while? the journalist suggested. Jean-Yves Nau last May. A month later, Emmanuelle Charpentier, who is now head of the Department of Infectious Biology at the Max Planck Institute in Berlin, spoke to the Academy of Sciences stating that "this technique works so well and is so successful that it would be important to evaluate the ethical aspects of its use".
A summit of major American, Chinese and British learned societies on human gene editing is scheduled for December in Washington.
 
Ethical issues are compounded by a fierce legal competition as to the ownership of the patents on this technology. For the stakes are colossal both in the field of health and agriculture. However, it will be necessary to distinguish between human and non-human applications, agricultural or microbiological, food or non-food, useful or futile, in order to avoid amalgamation and sterile polemics.
 
GMO or non-GMO?
 
The CRISPR/Cas process has become essential in the food industry. It revolutionizes mutagenesis which has been practiced by seed companies for more than 60 years. Instead of generating mutations using ionizing rays or chemical agents blindly and then selecting plants with the desired traits (which takes several years), the tool makes it possible to mutate a specific gene in a few weeks. Through this approach and related techniques, (Zinc Finger, TALENs, marker selection...) have been developed and then authorized on the American market of apples genetically modified in this way and called ArticApple (approved by the FDA in March 2015). The flesh of this one does not brown because a gene (responsible for the expression of polyphenol oxidase (PPO) has been silenced. Arctic" apples received a lot of media attention when the Canadian Food Inspection Agency published on its website (May 2, 2012) the application for authorisation in Canada submitted by the Okanagan10 requesting the comments of the public.
 

Arctic Apple
 
An InnateTM Potato, produced by J. R. Simplot Company is also consumable on the American markets since April 2015. It contains little asparagine, an amino acid that generates cancer-causing acrylamide during cooking.
 
In the pipeline are scab-resistant apples, scab-resistant apples, scab-resistant apples, scab-resistant apples, scab-resistant apples, scab-resistant apples.low phytate barley (phosphorus components of plants that are not digestible by farm animals) to make phosphorus more available for assimilation, fast-growing poplars for use as biofuels ... not to mention the modification of microorganisms such as yeast or microalgae to make them produce molecules of interest (morphine or antibiotics produced by Eligo Biosciences), ethanol or other biofuels, or to make them swallow C02 (Carboyeast by Denis Pompon at TWB). Two start-ups in France, Abolis and Bgene, produce microbial strains on a contract basis for major groups.
 
When CRISPR/Case becomes a regulatory puzzle
 
In the face of these developments, a nagging question deafens: are these modified organisms GMOs? Are they going to have to follow the assessments and legislation concerning them?
Clearly, should these interventions that confer new functions be subject to precaution because of possible unexpected effects?
As a reminder at the European level, the 1990 Directive defined a GMO as "an organism in which the genetic material has been altered in a way that does not occur naturally by recombination or natural recombination". Organisms resulting from classical mutagenesis were excluded, considering that these methods do not introduce any interspecies transfer in particular. Thus, seed companies propose to assimilate CRISPR/Cas (and related techniques) to classical mutagenesis (which do not introduce any gene foreign to the variety) and to assimilate these organisms as non-GMO.
But there are differing opinions on the subject. Committees to examine this question are multiplying in Washington, Brussels, in ministries, and research institutes. And the High Council for Biotechnology in France is going to have to mobilize on these controversies. With the most complex questions: If we avoid mutagenesis in all directions as in the past, are we in a better controlled production? Are these interventions having no effect on ecosystems or health? What means do we have to monitor these productions?
 
 
This mobilization is taking place against a backdrop of massive investments in the sector under the banner of "synthetic biology". Life sciences engineering is becoming the strategic challenge in the United States, where it could reach an amount of one billion dollars this year, if public and private funding is combined. There are 200 companies in the sector. For the past two years, high-tech billionaires such as Peter Thiel, co-founder of Paypal, and Eric Schmidt of Google have been turning to biotechnology," says Corine Lesne in her report. The synthetic biology boom. It points out that DARPA, the Pentagon's Agency for Advanced Defense Research, alone provides 60% of public funds. This effort includes only a tiny component of health and environmental studies (1% of the funding). The public is also kept away from these projects since only 23% of Americans (and 17% of Europeans) have any idea about synthetic biology (according to a survey by the Woodrow Wilson Institute in Washington). "We're in this strange situation where there's more money and inadequate regulation," says David Rejeski, director of the Science and Technology Innovation Program at the Woodrow Wilson Institute.
 
Europe mobilised and stuck in the doldrums
 
In Europe, programmes have been set up to promote synthetic biology and bioeconomics. Synenergene for example, is illustrated in France by the Living Festival Project which questions the industrialization of living things and the American hold reducing the diversity of approaches) in Vienna by the Biofiction Festivalor in Freiburg from theater... The creative process between scientists and artists StudioLabProject also shows synthetic biology.
It is regrettable that meetings on the subject remain confidential in France, in particular the one at Biocitech on November 27th organized by AlEnvi. It takes the initiative of the NGO ETC Group and the What Next Institute to hold a discussion on the governance of these biotechnologies in Geneva on 9 December next (3).
 
In the genetic community, voices are being heard calling for a new "Asilomar Conference». This meeting (of 130 geneticists behind closed doors) was held in 1975 and called for a moratorium on "genetic manipulation" to avoid uncontrolled GMOs in the environment. A member of the National Consultative Ethics Committee, Patrick Gaudray does not believe in the relevance of a moratorium: "I knew the beginnings of "genetic engineering", the moratorium of 1975 and the Asilomar conference.he explains. And I have observed that nothing was avoided, that the public debate on GMOs never took place, and that, with a little bit of bad spirit, one can see the breathing time that was necessary for technologists (Americans, in particular) to get their act together and become hegemonic. I do not believe in the purity of the reflection and moratorium announcements published in the two major scientific journals (Nature and Science) which rejected the article by the team led by Junjiu Hua. "
 
In this teeming context, France, the world's leading seed exporter, has every interest in making projects legible, accessible and criticizable, as Canadians understand it with their "ArticApple". The platform GENIUS  which raises the issue of utility (Useful plants and sustainable agriculture) coordinated by INRA is perhaps the beginning of a dialogue. Financed to the tune of 21.3 million euros for 7 years, it aims to "experiment with the social construction of projects", dear to Christian Huygue, Deputy Scientific Director of INRA.
 
 
 
(1) Martin Jinek, Programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunityScience, vol. 337, No. 6096, August 2012, pp. 816-821.
(2) Jiang et al, RNA-guided editiong of bacterial genomes using CRISPR/cas SystemsNature Biotechnology, 2013
(3 ) Governing Biotech 2.0:   How Synthetic Biology will Impact Rights, Livelihoods and LifeInternational Labour Organisation, 9 December 2015, Geneva.
 
 

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