an e-mail, pointing out Félix d’Herelle, who together with his colleague John Burdon Sanderson Haldane will be mentioned in more detail later; both published essays, already in the 1920s about viruses as the possible origin of life. At that time d’Herelle had just discovered the phages, the viruses of bacteria. Immediately, the two researchers speculated that viruses, which can self-reproduce, are the “primordial origin” as Darwin called it. I share their vision. However, their contemporaries rejected this idea vehemently.
Every year the New York agent and publicist John Brockman asks leading scientists an annual question, “The Edge”, about the knowledge of tomorrow. “What we believe but cannot prove: Today’s leading thinkers on science in the age of uncertainty” was the question in the year 2005. My answer would have been: Viruses got here first!
This requires a definition of what viruses exactly are.
Looking back
What is a virus? First of all, the word “virus” in Latin means sap, slime, or poison.
A colleague — Eckard Wimmer from Stony Brook in the USA — studies one of the smallest human virus particles, the one that causes polio, which contains 3,326,552 carbon atoms, 492,288 hydrogen atoms, 1,131,196 oxygen atoms, 98,245 nitrogen atoms, 7501 phosphorus atoms and 2340 sulphur atoms. Because it is possible to set out this molecular-style description, he designates the virus as a chemical, at least as long as it resides outside of the cell. Inside the cell it is not really only a chemical any longer, since it replicates itself and multiplies. Such a separation into two life forms is quite unique. Are then humans also only chemicals? That cannot be the answer.
It was just 120 years ago that viruses were first transmitted experimentally, causing diseases. The filtrate of sick tobacco leaves was transferred to healthy ones, which in turn became infected. The discoverer was the Russian botanist Dmitri Ivanovsky in 1892. However, he always believed that he was looking at something related to bacteria. It was therefore the Dutch microbiologist Martinus Beijerinck who is credited with the discovery of viruses, even though he himself acknowledged Ivanovsky’s work. Beijerinck coined the word “virus” to distinguish them from the larger bacteria, which cannot pass through the filters, the so-called Cham-berland filters, where only the small viruses run through. In animals, Friedrich Loeffler and Paul Frosch discovered almost at the same time — in 1898 — a transmissible small agent causing foot-and-mouth disease in cattle. The virus infects cows and is extremely contagious, and for that reason the first research institute for studying this virus was founded on a peninsula in the Baltic Sea. However, the wind was enough to spread the virus even from there. This research institute, named after the two aforementioned pioneers the LFI, is the biggest of its kind in Europe. Its reopening a few years ago attracted so many curious people that finally nobody could get there because of the traffic jam. The sterilization chambers (autoclaves) there are big enough to disinfect cadavers of whole cows.
Until recently it was taken for granted that all viruses are small, are nanoparticles, can only be detected in the electron microscope, cannot be kept back by filters, and contain either RNA or DNA often within symmetrical protein structures such as icosahedra; they do not replicate by themselves, they are parasites, they need cells within which to replicate, they cannot perform protein synthesis and they need energy from the cell. They are mostly specialized to living in certain hosts, and are sometimes covered by a coat that can be derived from the host cell and which often also carries receptors for binding to specific host cells. They are pathogens, cause diseases, are dangerous, steal their genes from the host, betray and abuse their host cells for the benefit of their own progeny, use disguises and hide in Trojan horses. In short: Viruses are enemies.
In recent years we have found out that almost all of this is wrong. Viruses are not only small; they can be bigger than many bacteria. Viruses themselves can be hosts of viruses, can be much bigger than nanoparticles — or even much smaller; in fact, they are not always particles! They can have sizes varying by a factor of 10,000 — a very broad range — they have very different morphologies, about a dozen different types of genomes, and a variety of totally different replication strategies. The number of genes that a virus can have reaches from zero (!) to 2500 — for comparison, humans have 20,000, only ten times more. “Zero genes” are present in viroids — though these are not generally accepted to be viruses. There are viruses that consist only of nucleic acids, without proteins, or (the other way round) only proteins without nucleic acids. The latter are the prions, which are often not considered as viruses either, but I would like to include them as well. There are viruses that have only foreign genes and none of their own, such as the very exotic plant viruses, poly-DNA-viruses (or polydnaviruses PDVs), a fact that may tell us something about evolution. Then there are the endogenous viruses, which never leave their host cell, and the rudimentary viruses that jump around in our genomes. These two types of virus do not have coats and are therefore locked-in viruses, unable to move between cells.
Viruses are mobile (genetic) elements — is that perhaps a useful definition? Viruses need energy, yes, but not necessarily from a host cell. Chemical energy will do, and that can come from around the black smokers, where life may have started and where no sunshine ever reaches. Viruses need niches, compartments, clay as catalysts — Darwin’s warm little pond — so that the concentration of components can be high. Such a first kind of containment could have been lipid bags, and one can ask whether this was an early virus or an early cell. There was initially no sharp boundary between viruses and cells — rather, they together make up a continuum. Especially the newly discovered giant viruses break taboos, because they are almost bacteria; they even have a hallmark normally only assumed to exist in bacteria: components for protein synthesis. This is often used as a definition of life, the ability to synthesize proteins. Thus these “almost-bacteria” represent a transition between viruses and bacteria, between lifeless and living. The discovery of giant viruses has revolutionized our view of viruses and has shifted viruses more towards “life” than had previously been assumed. A minimalistic definition of viruses includes their inability to perform protein synthesis, which is regarded as a hallmark of life. But the giant viruses can “almost” synthesize proteins — after all!
Viruses are found wherever life is. Viruses can take up and deliver genes, can mutate, recombine, insert, delete, or mix genes. Their replication is error-prone and therefore innovative for the virus and the host. Tumor viruses can pick up genes from the cell and mutate them during replication, which can increase their oncogenicity. But the opposite is also true: they can deliver genes to the cell, supplying new features, sometimes beneficial and sometimes detrimental. They can bring oncogenes into a cell and cause cancer, or they can introduce genes to cure cancer. More genes go into cells than come out. Viruses do not cause “wars” or lead to “crossing swords” or “arms races”; these negative descriptions are inadequate. They play ping-pong with their host. Horizontal gene transfer, between microorganisms and all other living hosts have led to complicated genomes. This is how our genome became such a colorful mixture of genes from very different other organisms and other genes. Every organism has a complex number of genes taken over from many other organisms, most frequently in fact from viruses. The viruses have by far the largest repertoire of genes, the largest sequence space available on earth — most of it is not even used. Viruses have a higher variety of genes than cells have, supporting the assertion that viruses were first on the scene, earlier than cells (more about that later).
How far back do we know about viruses? Let’s go backwards. 35 years ago HIV started to invade the human population, so far causing more than 37 million deaths. 100 years ago the influenza pandemic during World War I killed perhaps up to 100 million people. Measles killed the Mayas after being imported from Europe by the conquistadores. During the Middle Ages plague bacteria killed one-third of all Europeans, about 25 million people. Some 600 years earlier, in 542, the “Plague of Justinian” devastated Rome and spread as a pandemic around the Mediterranean Sea to Constantinople, at its height killing 6000 people there each day. Thucydides described an unknown disease in Athens during the Peloponnesian War in about 400 B.C. which could have been caused by Ebola, pox, measles or other viruses, or pesti bacteria. An Egyptian Pharaoh must have suffered from polio virus 3500 years ago as can be judged from a crippled leg