Viruses: little packages of software with clues to the mystery of life

The Novel Coronavirus SARS-CoV-2, yellow, emerging from the surface of cells, blue/pink, cultured in the lab. Also known as 2019-nCoV, the virus causes COVID-19.

Viruses have been getting rather bad press lately, but where would we be without them? A significant fraction of the human genome, it turns out, is actually of viral origin.

For millions of years the innards of long-vanished viruses have inveigled themselves into the DNA of our ancestors, and scientists are only just beginning to work out the functions of these ancient invaders.

We tend to think of viruses as menacing parasites, but this is a misunderstanding. The vast majority of them have no direct bearing on human health. Most viruses prey on bacteria, when they are known as phages. It’s not known how many types of viruses there are in all but it could be upwards of a million. The Earth is teeming with them; they are in the air, the soil and the sea. The oceans are in effect viral soup. It’s estimated that in total there are ten million trillion trillion phages out there, making them by far the most abundant biological entities.

Some viruses are positively good for our wellbeing. The human gut and other organs host a rich ecosystem of microbial cells, far outnumbering our own cells. Known as our microbiome, it plays a crucial role in maintaining our health. Recently it has been found that there is a corresponding “virome” there too, a whole realm of biological dark matter swarming in, and over, our bodies. What these countless trillions of viruses are doing is still poorly understood, but some seem to be part of the body’s defensive shield against harmful bacteria.

The beneficial effects of certain viruses are being widely explored for therapy. Because they can infect and destroy microbes they could be a vital substitute for antibiotics when bacteria evolve resistance. Others viruses are being used to target cancer cells, with more than 100 clinical trials under way. In a major advance, the US Food and Drug Administration has approved the use of a herpes virus for treatment of advanced melanoma.

As to all that ancient viral DNA now incorporated in our own genomes, scientists are still struggling to learn what it does. Many of the segments are simply harmless fossilised relics, but some have been co-opted to fulfil important functions. One example is in regulating the placenta. Placentas are an evolutionary innovation dating back 130 million years, crucial to mammalian embryo development and live birth. A gene known as Syncytin-1, which controls the separation of foetal and maternal tissue, turns out to be a repurposed gene from a retrovirus — the class of viruses that causes HIV. This useful gene seems to be just the tip of an iceberg, and some developmental biologists suspect a more pervasive role of retroviral genes in placental evolution, and even in the regulation of birth timing.

But it seems that viruses play a much more fundamental role in nature, not merely for the wellbeing of individual organisms but as a key part of the life-support system of the whole planet. Just as there is a human microbiome keeping us healthy, so there is a planetary microbiome helping to maintain the habitability of Earth. And here, too, viruses are key. Being highly mobile, they spread their influence around the world, like little genetic messengers. Because they can convey genes between cells — horizontal gene transfer — viruses form a crucial part of the mechanism of biological evolution. Forest Rohwer and his research group at San Diego State University call viruses the winners in the game of life: “That which controls the microbes — the phages — runs the world.”

Why do viruses exist in the first place? The answer can’t be separated from the profound and still unresolved question: what is life? One popular definition is Life = Chemistry + Information, which roughly corresponds to Life = Hardware + Software. Cells serve as the hardware, while genes — instruction sets digitally coded into segments of DNA — constitute the software. Viewed this way, viruses are essentially little packages of biological software — just a strand of DNA or, its cousin, RNA, encased in a protective coat.

When a virus invades a cell, it is analogous to your computer downloading a new application. It may cause the computer to crash, or it may confer new and useful functionality.

There is an old debate about whether viruses are alive. This question is a bit like asking whether a digital music app like iTunes can play a melody. Software on its own is helpless, but load a file into the right hardware and it can function — and be repeatedly copied.

In the same way, an isolated virus is inert, but inside a customised host cell it can spring into action, co-opting the manufacture of proteins and ordering the cell to churn out a huge number of viral replicas.

What is unclear is when viruses first arose. The origin of life on Earth remains one of the great unsolved problems of science. Did the hardware — cells of some sort — come first, or were informational molecules such as DNA and RNA already in existence?

Researchers are divided, but a popular theory is that there was an “RNA world” predating cellular life. If so, it’s possible that viruses are time capsules from that primordial phase. Indeed, they could have been indispensable participants in the incubation of cellular life itself, four billion years ago, and may carry important molecular clues to its genesis. None of this fascinating science diminishes the fact a handful of viruses make us sick. Life is a constant arms race against an unseen enemy.

Managing the pandemic is obviously the immediate priority, but COVID-19 is not the first global infection and it will not be the last. The biosphere is the original World Wide Web, with viruses and microbes forming a vast network of information exchange on a planetary scale. Sound public health policy depends on a thorough understanding of the bigger picture and the crucial place of viruses in the great story of life on Earth.

Paul Davies is a regents professor at Arizona State University and author of The Demon in the Machine: How Hidden Webs of Information are Solving the Mystery of Life, published by Penguin.