DuPont Nutrition & Health │ Dangé-Saint-Romain, France
For the foundational discovery of the role of CRISPR-Cas as a microbial system of adaptive immunity that has been developed as a powerful tool for precise editing of diverse genomes.
2018 Bower Science Award Theme: Genome Editing
Theme: Genome Editing
While studying yogurt bacteria, Philippe Horvath discovered a gene-editing mechanism that could lead to cures for some of the world’s most prevalent diseases.
Perhaps the biggest story in the world of biology during the past decade has been the discovery and development of the CRISPR-Cas9 system and its amazing utility as a tool for genetic engineering. This breakthrough, with far-reaching implications that scientists are only beginning to understand and explore, unlocks our ability to alter the workings of life with a precision that seemed impossible just a decade ago. Such major advances in science are rarely the work of a single individual, arising instead from the collaborative effort of many researchers. However, this revolution would not have occurred had it not been for the elucidation of a system that bacteria use to defend themselves against viruses. This is where Philippe Horvath became a crucial and foundational figure in the CRISPR-Cas9 story—even though his contribution unexpectedly began while trying to find a better way to make yogurt.
CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is a naturally-occurring part of the genetic system of bacteria, consisting of clusters of short regularly repeated pieces of DNA separated by variable DNA spacers. It functions as part of the adaptive immune system of these prokaryotic organisms, defending them from attack by viruses, although this was only a hypothesis before the work of Horvath's team was reported. His impact on understanding CRISPR began while he was working in the lab at Danisco (now part of DuPont) in France, investigating how Streptococcus thermophilus, a bacterial species commonly used to make yogurt and cheese, defends itself against bacterial viruses. Horvath deciphered the immune function of CRISPR, showing that it actually incorporates pieces of DNA from attacking viruses into the bacterial DNA as CRISPR spacers to protect against subsequent assault.
Although the title of Horvath's seminal 2007 Science paper, "CRISPR provides acquired resistance against viruses in prokaryotes," neatly sums up his discovery, it hardly indicates its depth and importance. For example, the paper showed that the cas9 gene—then called cas5—was required for immunity of the bacteria. Research made it further apparent that bacteria need a precise match between the acquired spacer DNA and the viral DNA to be immune. Horvath's demonstration of CRISPR's mechanisms proved to be the spark for an explosion of new scientific work into numerous aspects of the system, inspiring brand new avenues of exploration. Three years after his Science paper was published came the discovery that the Cas9 protein could be used as a means for cleaving a target with the precision of a molecular pair of scissors. A couple of years later, scientists discovered that it could be reprogrammed to cleave targets of interest. Formerly a rather hit-or-miss or difficult proposition, scientists could now perform gene editing with simpler components and surgical exactitude. By 2013, scientists used the CRISPR-Cas9 system to edit the human genome.
Until Horvath's work, CRISPR was an intriguing curiosity and its nature a matter of speculation. His demonstration of its vital role and basic function revealed it to be far more significant than most had previously suspected. Horvath’s seminal research laid the foundation for a flurry of subsequent work on CRISPR-Cas, sparking a tsunami of scientific discovery. Building upon Horvath's achievements, researchers have repurposed CRISPR into a new tool of unimaginable power and potential for humanity.
Unlike many other biologists responsible for revolutionary discoveries, Horvath has spent his career not as an academic scientist but working in industry, chiefly as a molecular biologist and food scientist. Educated at the Université Louis Pasteur in Strasbourg, France, he conducted his CRISPR research while at Danisco and continued to publish further important studies on CRISPR. These include his involvement in the research that showed Cas9 was cleaving the target DNA, and that a special bit of DNA needed to be adjacent and his participation as a collaborator on one of the first CRISPR reprogramming reports. His recognition of the fundamental significance of his work as well as its immediate relevance to the commercial applications of his industry testifies to his unique talent as a scientist.
Philippe Horvath is universally regarded as one of the key figures of the CRISPR-Cas revolution. His work has been highly cited and he holds nearly a hundred patents arising from his discoveries and professional work. He is a singular example of the truth that scientific creativity and intellectual brilliance are not limited solely to the halls of academia.
Information as of March 15, 2018