Ten seminal virologists

beijerinckIn my recent keynote address to the Brazilian Virology Society entitled The World of Viruses, I presented my list of ten seminal virologists. The idea to include such a discussion came from David Baltimore, who sent me the following note:

Since you have been thinking about the history of virology, I thought I would share a list with you. Someone asked me to list the 10 most important virologists in history. I came up with 12. But I wondered if you had to make such a list, who you would include.

David Baltimore’s list included the following individuals:

  • Jenner– the father of vaccination
  • Beijerinck– discovered the first virus
  • Rous– discovered tumor viruses
  • Enders– father of the polio vaccine, discovered how to grow viruses in cell culture
  • Lwoff– demonstrated latent infections with bacteriophage lambda
  • Stanley– first virus crystals
  • Klug– with Casper, described the principles of virus construction
  • Dulbecco– established the plaque assay for animal viruses, allowing quantitation– also found that tumor viruses integrate into host DNA
  • Delbruck– established viral genetics and, with Luria, was a father of molecular biology
  • Temin– suggested that there was a DNA intermediate in the growth of RNA tumor viruses and found the reverse transcriptase
  • Baltimore– found the first RNA-dependent RNA polymerase and the reverse transcriptase and established biochemical methods of virus investigation
  • Hilleman– made most of the vaccines in use today while working at Merck

Obviously such lists are very personal and will certainly differ (although there would likely be names in common). Here is the list of ten seminal virologists:

  • Beijerinck
  • D’Herelle – discovered bacteriophages
  • Theiler – produced the first infectious attenuated viral vaccine, yellow fever
  • Delbruck
  • Lwoff
  • Hershey – showed, with Martha Chase, that DNA carries the genetic information of bacteriophages
  • Enders – propagated an animal virus, poliovirus, in non-neural cell cultures
  • Klug
  • Baltimore
  • Doherty – discovered MHC restriction of T cell killing

I sent my list to David, who replied:

I suppose this is a discussion that could go on endlessly but I find Doherty a very odd choice (more an immunologist than virologist) and Hershey a surprising choice, although he makes sense for having shown that the guts of a virus is its nucleic acid. And I miss Rous and Stanley very much. When Stanley crystallized TMV he brought together chemistry and virology, made life a continuum from the inorganic and put viruses at the cusp. Then Hershey makes sense because he got inside the virus and found the key chemical. Rous, you might argue, did more for cancer research than for virus research but I still think that the link of viruses to cancer changed the trajectory of virus research.

Interesting discussion.

Rich Condit and Alan Dove also have their own lists of ten virologists, which we’ll share on an upcoming TWiV. Making such lists stimulates valuable discussion about discoveries that set the future course of virology. It’s very much like the discussion about whether or not viruses are alive – the answer is not as important as the thoughts involved in getting there.

Who would be on your list of ten seminal virologists?


TWiV 114: Ten out of ’10

vaccinia plaqueHosts: Vincent RacanielloAlan Dove, and Rich Condit

On episode #114 of the podcast This Week in Virology, Vincent, Alan, and Rich revisit ten compelling virology stories of 2010.

Click the arrow above to play, or right-click to download TWiV #114 (64 MB .mp3, 88 minutes).

Subscribe to TWiV (free) in iTunes , at the Zune Marketplace, by the RSS feed, or by email, or listen on your mobile device with Stitcher Radio.

Ten virology stories of 2010:

  1. XMRV, CFS, and prostate cancer (TWiV 113, 99, 98, 94, 89, 76, 70, 65)
  2. The ongoing saga of polio eradication (TWiV 110, 79)
  3. Viruses interact with the miRNA/siRNA system (TWiV 108, 72)
  4. Endogenous viruses – retro and beyond (TWiV 105, 91, 88, 65)
  5. Dengue virus progress and new outbreak (TWiV 111, 95, 82)
  6. Colony collapse disorder (TWiV 104)
  7. David Baltimore (TWiV 100)
  8. Ode to a plaque (TWiV 68)
  9. Vaccine contamination with circovirus (TWiV 86, 77, 75)
  10. Universal influenza vaccines (TWiV 107)

Weekly Science Picks

Rich – Elementary schoolchildren publish a science paper (original article and editorial with video) – thanks Kathy!
Alan – White-nose syndrome blog
Vincent – Headway, headlines and healthy skepticism

Send your virology questions and comments (email or mp3 file) to twiv@microbe.tv or leave voicemail at Skype: twivpodcast. You can also post articles that you would like us to discuss at microbeworld.org and tag them with twiv.

Simplifying virus classification: The Baltimore system

baltimore-classificationAlthough many viruses are classified into individual families based on a variety of physical and biological criteria, they may also be placed in groups according to the type of genome in the virion. Over 30 years ago virologist David Baltimore devised an alternative classification scheme that takes into account the nature of the viral nucleic acid.

One of the most significant advances in virology of the past 30 years has been the understanding of how viral genomes are expressed. Cellular genes are encoded in dsDNA, from which mRNAs are produced to direct the synthesis of protein. Francis Crick conceptualized this flow of information as the central dogma of molecular biology:

DNA —> RNA —> protein

All viruses must direct the synthesis of mRNA to produce proteins. No viral genome encodes a complete system for translating proteins; therefore all viral protein synthesis is completely dependent upon the translational machinery of the cell. Baltimore created his virus classification scheme based on the central role of the translational machinery and the importance of viral mRNAs in programming viral protein synthesis. In this scheme, he placed mRNA in the center, and described the pathways to mRNA from DNA or RNA genomes. This arrangement highlights the obligatory relationship between the viral genome and its mRNA.

By convention, mRNA is defined as a positive (+) strand because it is the template for protein synthesis. A strand of DNA of the equivalent sequence is also called the (+) strand. RNA and DNA strands that are complementary to the (+) strand are, of course, called negative (-) strands.

When originally conceived, the Baltimore scheme encompassed six classes of viral genome, as shown in the figure.  Subsequently the gapped DNA genome of hepadnaviruses (e.g. hepatitis B virus) was discovered. The genomes of these viruses comprise the seventh class.  During replication, the gapped DNA genome is filled in to produce perfect duplexes, because host RNA polymerase can only produce mRNA from a fully double-stranded template.

The Baltimore classification system is an elegant molecular algorithm for virologists. The principles embodied in the scheme are extremely useful for understanding information flow of viruses with different genome configurations. When the bewildering array of viruses is classified by this system, we find fewer than 10 pathways to mRNA. By knowing only the nature of the viral genome, the basic steps that must occur to produce mRNA are readily apparent. More pragmatically, the system simplifies understanding the extraordinary life cycle of viruses.

Crick FH (1958). On protein synthesis. Symposia of the Society for Experimental Biology, 12, 138-63 PMID: 13580867

Baltimore D (1971). Expression of animal virus genomes. Bacteriological reviews, 35 (3), 235-41 PMID: 4329869