Microscopic image of SARS-CoV-2, the virus that causes covid-19 (highlighted in blue).
Microscopic image of SARS-CoV-2, the virus that causes covid-19 (highlighted in blue).
Image: CDC

As the world struggles to contain covid-19, we’re reminded of the ways viruses aren’t like other organisms. In fact, these tenacious microbes defy traditional notions of life itself.

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Fewer things are scarier than an unrelenting invisible enemy, but such is our predicament in the ongoing battle against SARS-CoV-2, the virus that causes covid-19. This ain’t our first rodeo, of course, as humanity has already dealt with its fair share of viral pandemics throughout history. Viruses, fair to say, are an indelible part of the human condition.

Viruses have an eerie quality to them, exhibiting characteristics incompatible with traditional definitions of life. Key to this debate is scientists’ inability to agree on a standard definition of life and what it means for something to be alive.

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Back in 1944, for example, physicist Erwin Schrödinger took a kick at the can, saying life is anything that resists entropy, that is, things capable of avoiding disorder and decay into equilibrium. A piece of matter becomes alive when it “goes on ‘doing something,’ moving, exchanging material with its environment, and so forth, and that for a much longer period than we would expect an inanimate piece of matter to ‘keep going’ under similar circumstances,” wrote Schrödinger in his book What Is Life?

It was a neat idea, but somewhat of an overreach, given that Schrödinger was clearly trying to squeeze out a definition by applying the Second Law of Thermodynamics to living systems.

Illustration of the novel coronavirus.
Illustration of the novel coronavirus.
Image: CDC

In 2010, biologists Peter Macklem and Andrew Seely defined life as a “self-contained, self-regulating, self-organizing, self-reproducing, interconnected, open thermodynamic network of component parts which performs work, existing in a complex regime which combines stability and adaptability in the phase transition between order and chaos, as a plant, animal, fungus, or microbe.”

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Um, that’s a mouthful and certainly confusing. A “phase transition between order and chaos,” sound more like a Tool lyric than science, to be honest.

To help astrobiologists identify extraterrestrial life should they ever encounter it, NASA developed its own definition for life, which is short and sweet: “a self-sustaining chemical system capable of Darwinian evolution.” Nice, but perhaps too simplistic.

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I could go on, but as the BBC pointed out in 2017, there are over 100 definitions of life, and they’re probably all wrong.

Indeed, as Nigel Brown, the former president of the UK’s Microbiology Society, told Gizmodo, there’s “no agreed definition of life that covers every aspect of living organisms.” For example, a typical criteria for life is that it be able to reproduce, but “a crystal seeding a liquid can reproduce itself,” he said, adding that “things like growth, a life cycle, metabolism, response to stimuli,” and other characteristics deemed necessary for life “vary between different organisms.”

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The vexing thing about viruses is that they exhibit both distinctly lifelike and un-lifelike attributes. At the same time, scientists can’t even agree as to where a virus, as a “living” entity, begins or ends, saying a distinction can be made between a “virion” and a “virus;” the former describes the inert particle itself, and it becomes a virus only once it infects living cells.

This is a fascinating point, requiring us to describe viruses and how they work.

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A Lego model of a bacteriophage, a type of virus that infects bacteria.
A Lego model of a bacteriophage, a type of virus that infects bacteria.
Image: Pascal (Wikimedia Commons)

Viruses can be construed as organized packages filled with proteins and genetic material, whether RNA or DNA. Like fish out of water, these microbes cannot do what they do in extracellular environments, that is, places without access to biological cells.

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Indeed, viruses need cells to survive—and it’s not because they feed on cells like some kind of microscopic carnivore. Rather, viruses hijack cells, appropriating and reconfiguring them into machines that spit out more viruses. In addition, viruses alter the the host organism itself, triggering a panoply of symptoms—like sneezing, coughing, congestion, or diarrhea—which confers mobility to the virus, allowing it to infect new hosts.

In some cases, these symptoms cause the death of the host, which really isn’t the intention of the virus. All the virus wants to do is replicate, and if it involves the death of the host, so be it.

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Given these strange features, it’s clear why some scientists might not want to slot viruses into the realm of the living: They can’t autonomously reproduce on their own, they need to appropriate foreign biological material to replicate, and they have no metabolism.

For these and other reasons, Amesh Adalja, an assistant professor at Johns Hopkins Bloomberg School of Public Health, doesn’t believe viruses are alive.

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Depiction of the measles virus.
Depiction of the measles virus.
Image: CDC

“I think of life as a self-generated and self-sustaining process,” Adalja told Gizmodo. “When you use that definition, viruses fall out because they are unable to be self-sustaining, unlike, for example, a bacterial cell. Though viruses possess genetic material, they are, in essence, inert until in contact with a host cell in which host cell contents act upon the virus.”

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Brown says viruses are not lifelike in that they’re basically “gift-wrapped nucleic acid,” namely genetic material surrounded by a protein coat, sometimes with a membrane stolen from the host. This coat “consists of proteins encoded in the viral nucleic acid, but synthesized using the host’s systems,” Brown told Gizmodo.

At the same time, Brown said, viruses are lifelike in that “they have their own genetic material and reproduce themselves by usurping their host’s metabolic capacity to produce a new generation of virus particles, which go through the next life-cycle of reproduction,” he told Gizmodo. “They also evolve by mutation.”

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This is very much the case for RNA viruses, like the influenza virus, which mutates rapidly, forcing us to deploy new flu vaccines each year, he said. Troublingly, the SARS-CoV-2 virus is also RNA-based, which likely means it’s susceptible to mutation.

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Three years ago, a paper published in Science Advances argued that viruses are indeed a form of life. Evolutionary biologist Gustavo Caetano-Anollés and his colleagues presented evidence showing that viruses most likely originated from early RNA-containing cells. The researchers compared the protein folds of thousands of viruses with many different cells in order to track the evolutionary history of the virus through time. Viruses, the authors concluded, are more related to cells than previously believed, with viruses and cells sharing a common ancestor.

What’s more, they argued that a virus by itself is not actually the whole virus. Rather, the “true ‘self’ of a virus is the intracellular virus factory of infected cells,” and not the viral particle itself, the virion, the authors wrote. That’s kind of profound when you think about it.

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Writing seven years earlier, biologist Patrick Forterre made the same argument:

It has been recognized that viruses have played (and still play) a major innovative role in the evolution of cellular organisms. New definitions of viruses have been proposed and their position in the universal tree of life is actively discussed. Viruses are no more confused with their virions, but can be viewed as complex living entities that transform the infected cell into a novel organism—the virus—producing virions.

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Viruses, according to this school of thought, are therefore capable of self-replication—they just go about it differently. Brown, on the other hand, doesn’t buy it, as he explained in a 2016 Microbiology Society article:

If a virus is alive, should we not also consider a DNA molecule to be alive? Plasmids can transfer as conjugative [connected] molecules, or be passively transferred, between cells, and they may carry genes obtained from the host. They are simply DNA molecules, although they may be essential for the host’s survival in certain environments. What about prions? The argument reductio ad absurdum is that any biologically produced mineral that can act as a crystallisation seed for further mineralisation (hence meeting the criterion of reproducibility) might also be classified as living!

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It’s a fair point, and reductio ad absurdum seems a pertinent complaint. Who’s to say, for example, that a virus under this view doesn’t also extend to the entire host organism itself, as the viruses can directly affect physiological behavior?

The question of whether viruses are alive or not, while a fascinating exercise, is likely to have little scientific bearing, but Adalja told Gizmodo that an important question remains in evolutionary biology about how viruses arose and whether they were “once forms of life that devolved to viruses” or the very progenitors of life itself, he said. As for Brown, he said the life/not-life debate is largely semantic and philosophical.

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Alive or not, there’s no argument that viruses affect the living—and that’s what really matters.

George is a senior staff reporter at Gizmodo.

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