Stanislav Dusko Ehrlich, the giant of microworlds

Pioneering work in microbiology

He receives the Agricultural Research Award for 2008.

One of his earliest accomplishments was his work in cloning DNA, in the 1970s. As a postdoctoral fellow at Stanford in the prestigious laboratory of Nobel laureate Joshua Lederberg, then using the Bacillus subtilis bacteria as a study model, Dusko Ehrlich sensed the importance of cloning techniques that would make it possible to transfer a given gene into a bacteria, multiply it, and study the functions of the protein for which it coded. Scientists first turned their attention to Escherichia coli, which had the advantage of having natural DNA vectors*.

Bacillus subtilis did not have this advantage, but it was an organism of choice for the study of protein secretions, not to mention an excellent model for the study of bacteria. To develop B. subtilis cloning techniques, Dusko Ehrlich found a vector in a relatively similar bacteria, Staphylococcus aureus. This initial success, which demonstrated that a plasmid from a different species could be used as a cloning vector, was published in the PNAS journal in 1978. His continued work in the field and his pioneering expertise in cloning won Dusko Ehrlich membership in the European Molecular Biology Organisation (EMBO) and recognition as a specialist in the field.

In the 1990s, another major step was reached with the sequencing of DNA. Dusko Ehrlich remained in France, where INRA had asked him to create the Microbiology Division. While pursuing his research on B. subtilis, Dusko Ehrlich also started studying lactic acid bacteria, which have practical applications. Noting the recent progress in DNA sequencing, particularly in E. coli, he decided to use the new techniques to gain a better understanding of the physiological characteristics of these bacteria. Dusko Ehrlich demonstrated that their inability to synthesise certain amino acids was not due to the lack of the corresponding genes, but rather their inactivity, as the genes were silenced. He postulated that such functions were lost during evolution, as lactic acid bacteria developed in casein-rich environments that supplied them with amino acids. More work followed. Dusko Ehrlich and his collaborators showed, specifically, that lactic acid bacteria had the equivalent of another gene identified in E. coli which conferred protective enzymatic activity against bacteriophage-induced degradation. The finding led in 1995 to the "first PNAS** dedicated to lactic acid bacteria". The work as a whole helped propel INRA to international prominence in the field of microbiology.

Advances and international recognition in microbial genomics

Persuaded that knowing the genome would explain many bacterial traits, Dusko Ehrlich set out to perform the systematic sequencing of the B. subtilis genome. The full sequence was published in Nature in 1997, the product of a consortium that included some forty laboratories from Europe, Japan and Korea. Dusko Ehrlich recalled the lively debate that took place when the project was launched and the skepticism it met among the heads of the National Institutes of Health. They believed that sequencing techniques were not advanced enough for the task. Nevertheless, by 1997, the genomes of about a dozen microorganisms had already been sequenced, with another forty on the way.

For Dusko Ehrlich, the benefit was obvious. "Almost 40% of genes have unknown functions and we understood that while it was relatively easy to induce mutations to inactivate genes, it was very difficult to discover their function. However, by inducing mutations gene by gene, we discovered that 271 genes were essential to the life of B. subtilis, 80% of which are found in known bacteria." This study led to a PNAS article (2003, 99 authors), which became the most cited in the field.

Objective assessment of his work's impact as a key to an exceptional scientific career

Stanislav Dusko Ehrlich and his team.© NICOLAS BertrandThroughout his career, Dusko Ehrlich sought to be both ambitious and realistic: the former by placing himself at the cutting edge of his field and surrounding himself with the best, the latter by an unsentimental assessment of his work. "For me, the best evaluation of scientific results combines the number of publications and the number of times each publication is cited," he explained. "Most articles are never cited. Meanwhile, research is even more relevant if the index of article citations for a given period is higher than the average index for the journal. There are rigorous methods for calculating these indices. These criteria should make it possible to assess the research efficicacy of a team, and, more specifically, to save time in attributing research credits."

Another key to success for Dusko Ehrlich is having a large enough team: 10 persons to be competitive at an international level, 50 to 60 persons – the size of his current research unit at INRA Jouy-en-Josas – to address applied aspects in addition to the fundamental aspects of a field. Research is global, and being at the top of the game requires time, work, and luck, because there's always an unforeseeable part to it. You need to be able to draw great satisfaction from a few successes among a plethora of daily failures. In short, we're "wrong" almost all the time and we need to work a lot to be "right" once in a while. Since 2005, Dusko Ehrlich has been behind a vast international project to sequence the genome of human intestinal bacteria, a project with invaluable consequences for health research.

*DNA vector: to clone a gene, scientists need to use a DNA vector that can transfer and multiply that gene in the target organism, bacteria, yeast or higher organism. These vectors are often derived from plasmids, which are circular DNA plasmids found naturally in some bacteria, and which are capable of multiplying independently.
**PNAS: Proceedings of the National Academy of Sciences (United States).