Читать книгу Viruses: More Friends Than Foes (Revised Edition) - Karin Moelling - Страница 27

The word “virus” often provokes disgust: “Ugh, keep that out of here” — or “Watch out, they’re contagious, they make you ill”! Yet here comes a book about the opposite: Viruses are better than their reputation. Much better. This is a surprising reverse side of the viruses, which will be the topic of this book. Viruses as friends, not foes!

Everything in virology is new. Unnoticed, a paradigm shift has taken place: the focus is no longer upon diseases, but rather on the positive side of viruses: viruses as drivers of evolution, viruses leading to innovation, viruses at the origin of life — or at least their presence from the very beginning. Throughout evolution viruses have been our “bodybuilders” or gene modulators. What is a virus? Where do viruses come from? Are they alive or not? Why and when do they make us ill? Whether you, the reader, want to continue swimming in the sea — whether babies’ dummies from the Far East may cause cancer and should be avoided — whether you should stop enjoying salad because of the many plant viruses — these are questions that you can decide upon for yourself after having read this book.

While reading it, you will learn something about life — the innermost parts of your cells and your genes; you will find out how viruses contribute to our adaptation to environmental conditions; you will be confronted with the question of whether they may contribute to human free will; you will discover the extent to which we are related to bacteria and worms, and how sex can be replaced by viruses; you will find out that viruses “invented” all immune systems and supplied cells with antiviral defense mechanisms. This is much easier to understand than you may expect, and it reflects my own thinking. What part do viruses play in cancer development and gene therapy? Do “jumping genes”, which are “locked-in viruses”, create geniuses? Do you know that viruses can “see”? Almost they do, the color blue! You will read about efforts to save chestnut trees, about where stripes on tulips and the white patterns on blue balcony petunias come from (viruses of course) and how viruses caused the first financial crisis, known as “tulipomania”. Finally, one-third of mankind may want to know how to control body mass or obesity. (By viruses? Yes, indeed.) The viruses have contributed, and are still contributing, to all of these. And now, let’s start by reading about the success story of the viruses.

HIV particles aligned at the cell surface, electron microscopic picture.

In 2009, Darwin’s bicentennial year, 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 also exist in astronomical numbers in the oceans, every salad dish is full of viruses — and they cannot be washed off, as they are inside the cells; yet they are harmless. Viruses are everywhere, and so are bacteria and probably also all other microorganisms — and this is not in the context of diseases. All this knowledge is new; it goes back to the beginning of our century, and we owe it to the new technology, the sequencing of genes — which has become millions of times cheaper and faster within the past ten years.

Humans are a superorganism, a complete ecosystem. Healthy humans comprise 10¹³ cells which are authentically human, our “self”, and in addition we host about 10¹⁴ bacteria and, in addition, at least ten to a hundred times more viruses. Our genome, consisting of about 20,000 to 22,000 genes is augmented by more than several millions of genes, 350 times higher than the number of our genuinely human cells. The microorganisms reside in our guts and populate our skin — we may ask whether they should be removed by a daily shower — I would say no! They are useful and protect us from foreign ones.

Viral and bacterial sequences have even entered our genomes. This seems unbelievable. How much is left of us as humans? The challenge of explaining this to as many people as possible was the reason for me to write this book.

Bacteria have been called our second genome. This is generally accepted. We shall have to add the viruses as our third genome. And then there are also millions of fungi. Are they our fourth genome? And what about the archaea? Yes, they certainly contribute as well.

This ecosystem is not characterized by a constant war — not by killing, but rather by a ping-pong game, by a well-balanced co-existence, by co-evolution. The “war” vocabulary has to be abandoned. Things only get dangerous when we destroy the balance. In most cases humans cause diseases themselves. Viruses and bacteria behave opportunistically. They take advantage of unusual situations, of weaknesses of their hosts. This description is as far as I would go; the “war” vocabulary I do not accept.

Another novelty has been the discovery of giant viruses, the mimiviruses, the biggest viruses ever encountered, bigger than many bacteria. These viruses can even play host to smaller viruses. They also have some properties in which they resemble bacteria. They were detected “mimicking” bacteria, which gave them their name “mimiviruses”. Thus the borderline between viruses and cells is not a sharp one, and the world of viruses and bacteria is a continuum. All known definitions of viruses have become obsolete. How are we to define a virus? What about the transition between living and non-living matter?