Heidelberg virologist receives the highest medical science award of the USA

September 2016

For his work on the propagation of the Hepatitis C virus in cell culture systems, Professor Dr. Ralf Bartenschlager receives the 'unofficial American Nobel Prize in Medicine'.

The virologist Prof. Dr. Ralf Bartenschlager, Executive Director of the Department of Molecular Virology at the Center for Infectious Diseases at Heidelberg University Hospital and Faculty of Medicine since 2002 and Research Director for Infection, Inflammation, and Cancer at the German Cancer Research Center since 2014, was honored with the Lasker-DeBakey Award for clinical medical research, along with his colleagues Professor Charles Rice, Rockefeller University, New York, and Dr. Michael Sofia, Arbutus Biopharma, USA. The Lasker award, awarded annually in three categories by the Lasker Foundation of New York, is the highest medical science award in the USA and is considered the 'unofficial American Nobel Prize of Medicine'. The endowment is $250,000. In 1999, the research team of Ralf Bartenschlager was initially successful in propagating a slightly altered form of the Hepatitis C virus within liver cells in the laboratory. This cell culture system produced the prerequisite conditions for the development of highly effective medications. The first of these medications worked solely to insulate the liver from inflammation. Since 2014, thanks to therapies targeting the HCV proteins, cure of more than 95% of patients with chronic Hepatitis C is possible.

"Today, chronic hepatitis C is curable in the majority of patients. Without the propagation system for this virus, developed by Ralf Bartenschlager and his team, on which initial testing of antiviral agents could be carried out, we would not be even close to this result now", said Professor Dr. Guido Adler, Executive Medical Director of Heidelberg University Hospital about the performance of the virologist, who has previously received multiple awards. Professor Hans-Georg Kräusslich, spokesman for the Center of Infectious Diseases and Vice Dean of Research, added, "The outstanding work of Ralf Bartenschlager and his team, and this award for this work, have invigorated the research focus on infectious diseases at the Heidelberg University Hospital Medical Campus".

Bartenschlager has researched the hepatitis C virus for 25 years

“For some reason, HC virus isolated from patients does not propagate in cell culture, and thus, we knew next to nothing about how it works", says Bartenschlager. “However, a cell culture system is indispensable, because viruses are intracellular parasites. As such, they can only replicate and thus, be investigated, within living cells.” The solution of the researchers: to create a genetic HCV 'mini-genome', or replicon. The trick was to endow this mini-genome with a resistant gene that would enable isolation from the millions of other cells, as well as highly efficient propagation of the replicon-containing cells. Using this foundation, the team has continued to improve the system over the years.

For the first time it was possible to investigate the molecular properties of the virus, to test potential medications, and to explore new targets for antiviral therapy. One example is the viral protein NS5A: “The function of NS5A was long unknown. It had no enzymatic activity, and was thus not considered a potential therapy target”, says the virologist. "Only the replicon cell system showed that it has multiple functions, like a Swiss Army knife. Agents that incapacitate NS5A are the most potent HCV blockers of all." One mechanism of action of this protein was clarified by Bartenschlager and his research group at Heidelberg University Hospital Faculty of Medicine, where in 2002 he took over as the Chica and Heinz Schnaller Foundation Chairman of Molecular Virology. Almost all currently used therapies for chronic Hepatitis C are based on the combination of an NS5A inhibitor with one of two other antiviral agents.

Further information:
Lasker Foundation
Study group Professor Dr. Ralf Bartenschlager at the Department for Molecular Virology, Heidelberg University Hospital
Video of the Lasker Foundation on the award winners and Hepatitis C research