one another, like a sneeze on the breeze, and died from it or else had to be culled. Friedrich Loeffler and Paul Froesch, at a university in northern Germany, using the same techniques of filtering and dilution as Beijerinck, proved in 1898 that the foot-and-mouth agent is also a filter-passing entity capable of replication only in living cells. Loeffler and Froesch even noted that it might be just one of a whole class of disease agents, so far undiscovered, possibly including some that infected people, causing phenomena such as smallpox. But the first viral infection recognized in humans wasn’t smallpox; it was yellow fever, in 1901. Around the time William Gorgas was solving the practical problem of yellow fever in Cuba, by killing off all those mosquitoes, Walter Reed and his little team of microbiologists showed that the causative agent was indeed mosquito-transmitted. Still, they couldn’t see it.
Scientists then began using the label “filterable virus,” which was a clumsy but more precise application of the old poisonous-slime word. Hans Zinsser, for example, in his 1934 book Rats, Lice and History, a classic chronicle of medical groping and discovery, declared himself “encouraged by the study of the so-called ‘filterable virus’ agents.” Many epidemic diseases, Zinsser wrote, “are caused by these mysterious ‘somethings’—for example, smallpox, chicken pox, measles, mumps, infantile paralysis, encephalitis, yellow fever, dengue fever, rabies, and influenza, to say nothing of a large number of the most important afflictions of the animal kingdom.” Zinsser realized, too, that some of those animal afflictions might overlap with the first category, human epidemics. He added a crucial point: “Here, as in bacterial disease, there is a lively interchange of parasites between man and the animal world.” Zinsser was a panoramic thinker as well as an acutely trained microbiologist. Eight decades ago he sensed that viruses, only lately discovered, might be among the most nefarious of zoonoses.
55
The difficulty of cultivating viruses in vitro made them obscure to early researchers, elusive in the laboratory, but it was also a clue to their essence. A virus won’t grow in a medium of chemical nutrients because it can only replicate inside a living cell. In the technical parlance, it’s an “obligate intracellular parasite.” Its size is small and so is its genome, simplified down to the bare necessities for an opportunistic, dependent existence. It doesn’t contain its own reproductive machinery. It mooches. It steals.
How small is small? The average virus is about one-tenth the size of the average bacterium. In metric terms, which are how science measures them, roundish viruses range from around fifteen nanometers (that’s fifteen billionths of a meter) in diameter to around three hundred nanometers. But viruses aren’t all roundish. Some are cylindrical, some are stringy, some look like bad futuristic buildings or lunar landing modules. Whatever the shape, the interior volume is minuscule. The genomes packed within such small containers are correspondingly limited, ranging from 2,000 nucleotides up to about 1.2 million. The genome of a mouse, by contrast, is about 3 billion nucleotides. It takes three nucleotide bases to specify an amino acid and on average about 250 amino acids to make a protein (though some proteins are much larger). Making proteins is what genes do; everything else in a cell or a virus results from secondary reactions. So a genome of just two thousand code letters, or even thirteen thousand (as for the influenzas) or thirty thousand (the SARS virus), is a very sketchy set of engineering specs. Even with such a small genome, though, coding for just eight or ten proteins, a virus can be wily and effective.
Viruses face four basic challenges: how to get from one host to another, how to penetrate a cell within that host, how to commandeer the cell’s equipment and resources for producing multiple copies of itself, and how to get back out—out of the cell, out of the host, on to the next. A virus’s structure and genetic capabilities are shaped parsimoniously to those tasks.
Sir Peter Medawar, an eminent British biologist who received a Nobel Prize the same year as Macfarlane Burnet, defined a virus as “a piece of bad news wrapped up in a protein.” The “bad news” Medawar had in mind is the genetic material, which so often (but not always) inflicts damage on the host creature while exploiting its cells for refuge and reproduction. The protein wrap is known as a capsid. The capsid serves two purposes: It protects the viral innards when they need protection and it helps the virus