I had lunch with colleagues from the Institute for Advanced Study in Berlin and, in conversation, asked them how they thought life started. They included philosophers, historians, sociologists and lawyers — so what did they suppose? The Big Bang? Certainly not Adam and Eve, they said — disdaining creationism. But their general response was one of perplexity and helplessness. If you are asking this question, one of the Fellows concluded, then the answer must have something to do with viruses. Yes, that is exactly what I think: Viruses were there at the beginning, or at least they contributed from very early on.
The history of medicine has led to a one-sided picture of the viruses, portraying them as causing various diseases. That is indeed how we came to know about them. Most viral diseases are incurable — no treatments are available against them — which contributes to the bad reputation of viruses. For centuries, people were helpless against viral infections. Polio, measles, pox and influenza have destroyed cultures, decided the outcome of wars, ruined cities and depopulated whole landscapes. Viral infections could not be distinguished from bacterial ones, in fact, that is not even necessary, because according to the newest research results pestis bacteria became as deadly as they are by modification through a phage, a virus that resides in bacteria.
There are commemorative “plague columns” in many cities — such as Vienna, where the Pestsäule is today a popular meeting-point. The church of Santa Maria della Salute in Venice reminds us of the Black Death in 1347, and the fear of infections and the gratitude of the survivors, even today. With colorful gondola parades, Venice commemorates the plague every year — even though that city never completely recovered from the high death toll. The Spanish Conquistadores owed their victory over the Mayas in Mexico mainly to measles, which was not known there and was therefore deadly for the local population. The Mayas avenged themselves by giving syphilis to their conquerors, and so to Europe. The outcome of World War One was decided at least in part by the influenza epidemic, with possibly up to 100 million deaths. Since 1981 HIV/AIDS has killed some 37 million people worldwide, and every year two million more become infected.
It has only been for the last 100 years that we have been able to distinguish viruses from bacteria. The easiest way is by their size: viruses are in most cases — we shall hear about exceptions — smaller than bacteria, and at least today they depend on cells for their replication, including mammalian or plant or bacterial cells. Bacteria, in contrast to viruses, can replicate autonomously. Today’s viruses cannot do that, but they may well have been able to do so in the distant past. Both bacteria and viruses can cause diseases. Antibiotics will destroy bacteria but not viruses. If doctors nonetheless prescribe antibiotics for viral infections, then this is to protect the patients against any possible bacterial superinfection. There are very many books about viruses describing them as causes of disease. For many years I taught exactly this to medical students at the Universities of Berlin and Zurich. But that is not what I am writing about here.
No, the opposite needs some attention. Thanks to new technologies, virology has changed completely since the beginning of this century. If viruses were once regarded as enemies of humans and animals, even of all life forms, we now recognize that viruses contributed to the beginning of life and have positively contributed to its development from then on, to this day. In the last ten years or so, our perception of all microbes — viruses as well as bacteria — has changed completely. New methods, new experimental approaches and new, sensitive detection methods have revealed that viruses are by no means only pathogenic germs. Shouldn’t we be surprised that viruses do not spread faster, leading to many more infections, when there are three billion flights worldwide each year, carrying about 300 billion passengers — despite the fact that the air in airplanes is only circulated around and not purified by expensive sterilizing filters. Most viruses and other microorganisms are harmless for their hosts — that is something to remember.
Viruses are everywhere. They are the oldest biological entities on our planet, as will be shown later. And they are also by far the most abundant. We were born as humans into a world which had existed for billions of years before us. We are latecomers, and have populated our planet for less than a few hundred thousand years. Those who were unable to cope with the pre-existing microorganisms died, and the others established a co-existence with them. We do not know how many populations have died out because of diseases — was Neandertal Man one of them? It is important to note: Diseases occur when a balance is disturbed and changes of environmental conditions occur through poor hygiene, traveling, overpopulated cities, disappearing forests, water reservoirs, pollution or close contact with other species that carry viruses unfamiliar to us (zoonosis). Microbes not known to an organism may cause diseases without affecting those who are used to them. Most of our human diseases are self-made — a strong statement! A simple example is that of catching a proverbial “cold” — which means a temperature change allowing some viruses to replicate better than before, leading to diseases such as rhinitis or influenza. “Catching a cold” — summarizes virology in a nutshell! We are normally in a well-balanced equilibrium with our environment, and diseases arise only if the balance gets out of control or conditions are unfamiliar. This gives viruses an opportunity to replicate and make us ill.
The new millennium started with a surprise. Two scientific publications changed our view of the world. One showed that viruses make up half of our genetic material, our genome, all of our genes, and the other revealed to us the dominance of microorganisms in our body and around us. These publications were both based on a new technology which became available toward the end of the last century: sequencing, the determination of the sequences of large genomes such as the human genome. The first of the two papers, in 2001, described the determination of our genes consisting of 3.2 billion building blocks, the nucleotides. This was the result of a gigantic effort, with a multimillion-dollar input. Nobody could have imagined what our genome is predominantly made of. The answer is: viruses. Around half of the human genome consists of viruses — or at least virus-related sequences or truncated viruses, or viral fossils that have inhabited our genome for millions of years. Other organisms may even harbor viral sequences that constitute up to 85% of their genes. Where is the limit? 100% — ? We will discuss that. More surprising is the fact that these virus-like elements can move, they can jump, our genomes are constantly changing. And yet another surprise is that all genomes of all species on our planet are interrelated. We are all relatives at the genetic level: flies and other insects, algae or plankton, worms, even baker’s yeast, bacteria, plants, fungi all the way to humans — and the viruses anyway — because they supplied many of the genes.
The consortium that had set out to compare many genomes in the Human Genome Project (HGP) presented this result, in one of the longest publications I have ever seen in the journal Nature.
Recently, new methods have allowed an estimate of the numbers of viruses on our planet. There are more viruses on Earth than stars in the sky: 1033 viruses, 1031 bacteria, “only” 1025 stars and soon about 1010 humans. We are the invaders in a world of microorganisms, and not the other way round. A gigantic number of microorganisms, bacteria, archaea, viruses and fungi populate our body and dominate in our environment. Bacteria and viruses are present in kilogram amounts in our intestines — yet without causing diseases. On the contrary, they help us to digest various — even essential — nutrients, which we otherwise would not be able to consume. They also cover our skin, mouth, vagina, toes, nails and birth canal, all with site-specific bacterial and viral compositions. This very surprising observation of the ubiquitous presence of microoganisms is the result of a recent large-scale analysis, sequencing of the human microbiome, in the Human Microbiome Project (HMP). In a way it is a follow-up of the Human Genome Project (HGP). “Microbiome” is a new word that means the sequence of all microorganisms combined, without knowledge of the individual ones present in a given sample. “Do them all” is the principle. This second epoch-making paper was published in 2010, and since then the microbiome and its role in the human gut, in nutrition, in health and disease including such urgent issues as obesity and even autism and, surprisingly, depression and even anxiety have attracted much attention. An associated question is that of our food — what is healthy food? Is it the same for Japanese as for Italians? We do not even know! And the viruses come in here, too: Viruses