Archive for November 23rd, 2010

Farewell, Frank Fenner!

23 November, 2010

While visiting the Australian National University in Canberra recently, I noticed in the lobby outside their Club dining room, a most interesting tapestry.  Interesting, because it looked like a colourised electron micrograph (it depicts myxomavirus), and because it had a plaque beneath it commemorating their own Professor Frank Fenner.  I was familiar with him because he authored an extremely useful book – Medical Virology – which I had used for educating myself and for teaching; I was also aware that he was an extremely eminent poxvirologist who had been active in the field for decades – and was still working despite having retired in 1979.

Variola virus, the agent of smallpox. Image courtesy Russell Kightley Media.

And then today I heard that he had died this week, at the age of 95.

Virology is still a young field, as I discover while trying to research its history for my sabbatical project: the concept dates only from 1898; only a couple of generations of scientists have been active in this field since it started – and Frank Fenner probably overlapped with nearly all of them.  He was born in 1914, which meant he was in at the morning of virology as we know it, while many of the first practitioners were still around – and he stayed active until very recently, when the science had changed almost out of all recognition.  He will be missed.

I am sharing this message that was sent out by the Director of the John Curtin School of Medical Research at ANU, where Fenner worked as an Emeritus Professor, as it is probably the best short account of his life.

“It is with great sadness that I communicate to you the passing of Professor Frank Fenner.

Frank John Fenner AC, CMG, MBE, FRS, FAA (born 21 December 1914, died 22 November 2010) was an Australian scientist with a distinguished career in the field of virology. His two greatest achievements are cited as overseeing the eradication of smallpox during his term as Chairman of the Global Commission for the Certification of Smallpox Eradication, and the control of Australia’s rabbit plague through the introduction of myxoma virus.

Professor Fenner was Director of the John Curtin School from 1967 to 1973. During this time he was also Chairman of the Global Commission for the Certification of Smallpox Eradication. In 1973 Professor Fenner was appointed to set up the new Centre for Resource and Environmental Studies at the Australian National University (ANU). He held the position of Director until 1979.

Professor Fenner has been elected a fellow of numerous faculties and academies, including Foundation Fellow of the Australian Academy of Science (1954), Fellow of the Royal Society (1958), and Foreign Associate of the United States National Academy of Sciences (1977). During his career Professor Fenner received many awards. Among these are the Britannica Australia Award for Medicine (1967), the Australia and New Zealand Association for the Advancement of Science Medal (1980), the World Health Organization Medal (1988), the Japan Prize (1988), the Senior Australian Achiever of the Year (1999), the Albert Einstein World Award for Science (2000), and the Prime Minister’s Science Prize (2002).

A man of decisive scientific action and strong opinions, Professor Fenner’s last interview with The Australian is extremely thought provoking and can be found here:

A summary of Frank’s remarkable career can be found here:

The last public recognition of Professor Frank Fenner’s accomplishments occurred here at JCSMR during the First International Meeting on Translational Medicine earlier this month: On 1 November 2010 Professor Fenner received a standing ovation by world leaders in academic medicine during the opening of the Conference and on 2 November 2010 he was recognized by the Conference as he and Sir Gus Nossal stood by their portraits, which hang side by side at the National Portrait Gallery. A picture of Professor Fenner at JCSMR taken on 1 November 2010 next to Gus Nossal is attached.

Further notices will be sent with information regarding Professor Fenner as plans to honor his accomplishments evolve.

With best regards,


Professor Julio Licinio
Director John Curtin School of Medical Research
The Australian National University
Canberra, ACT 2601, Australia ”

Thanks to Bertram Jacobs of ASU for sharing this with me.

Ed Rybicki

Integrating the enemy

23 November, 2010

Ever since I first discovered them as a student, sometime in 1976, I have found retroviruses fascinating.  Not quite as fascinating as Ebola, possibly, but captivating nonetheless.  The whole concept of a virus that converts a perfectly ordinary mRNA into dsDNA, then  inserts it into the host chromosome as a provirus in a eukaryotic version of lysogeny – was truly wonderful.

And as the years have gone by, I have seen no reason to lessen the feeling of wonderment: other

The Retroid Virus Replication Cycle

viruses – now called pararetroviruses, including both hepadnaviruses and plant viruses – whose replication  starts at a different position in the  cycle have been found; these and retroviruses have been integrated into a whole family of “reverse transcribing elements” – retrons – which include prokaryote transposons; HIV burst in on the scene, and suddenly we know so much about how the immune system works, because a virus messes with it so well.

But the actual mechanics of one particular process have consistently escaped elucidation – until now.  The 11 November issue of Nature contains, apart from only the second SF short-short story by a South African (kudos, Anand!), a Letter of great interest.

The mechanism of retroviral integration from X-ray structures of its key intermediates
Goedele N. Maertens, Stephen Hare & Peter Cherepanov
Nature 468,326–329 (11 November 2010) doi:10.1038/nature09517

To establish productive infection, a retrovirus must insert a DNA replica of its genome into host cell chromosomal DNA. This process is operated by the intasome, a nucleoprotein complex composed of an integrase tetramer (IN) assembled on the viral DNA ends. The intasome engages chromosomal DNA within a target capture complex to carry out strand transfer, irreversibly joining the viral and cellular DNA molecules. Although several intasome/transpososome structures from the DDE(D) recombinase superfamily have been reported, the mechanics of target DNA capture and strand transfer by these enzymes remained unclear. Here we report crystal structures of the intasome from prototype foamy virus in complex with target DNA, elucidating the pre-integration target DNA capture and post-catalytic strand transfer intermediates of the retroviral integration process. [my emphasis – Ed] The cleft between IN dimers within the intasome accommodates chromosomal DNA in a severely bent conformation, allowing widely spaced IN active sites to access the scissile phosphodiester bonds. Our results resolve the structural basis for retroviral DNA integration and provide a framework for the design of INs with altered target sequences.

Basically, these folk have managed to freeze-frame several different stages of the process in crystals, by clever use of synthetic DNA targets – and then solved the structures.  NOT trivial, and the pictures are absolutely superb.  So are the movies…but you need to subscribe to Nature to see those.

Harking back to a previous post – Entrance, Entertainment and Exit, anyone? –  the more we know about viruses, the more we can mess with them.  And this is a VERY good step along that road.