Are viruses even alive? 1- What is life?

Virus
A T7 virion, seen through cryo-electron tomography. Image from Hu et al., 2013

Virus literally translates to slime or poison in latin, a sufficient word to define these organisms. It is but a highly simplistic depiction of  a much more complex entity.  The current coronavirus pandemic is defining everyone’s life. There are thousands of articles and videos talking about coronaviruses, and we encourage anyone to get informed only from experts (epidemiologists, biomedical researchers, virologists, doctors…).

At On Elephants and Bacteria, we specialize in talking about the Tree of Life (see Strangers in the Animal Tree), and here comes a critical question: Where do viruses place in the Tree of Life? The question is highly problematic, specially considering that, as we know, viruses may not even be alive.

And there you may think: how can viruses not be alive? The fact is, that defining life is not as easy as one may think, and viruses do not follow the rules that all other living organisms do.

What is life?

1200px-Prague-golem-reproduction
Golems, in the jewish tradition, are animated anthropomorphic sculptures of clay. Fiction has toyed with the limits of being alive. Image from here.

The question, thus, is: what is life? And the answer would be simple: anyone would point out to humans, birds, trees (most surely), mushrooms (probably), lichens (what?)… the concept of life is widely entrenched in our subconscious, but when asked what makes something “alive”, not everyone is able to explain it, not even scientists.

Aristotle first recognized in De Anima(On the Soul) the uniqueness of humans, animals and plants, and discussed how the three were beings shaped by a soul. This is the first definition of life, but the concept of  a soul has been wacky at best, and so far has not found a place in our scientific understanding of life.

Defining life in scientific terms has been a troubling issue, and multiple authors, even non-biologists, have presented their own different, but similar views. As we explore the weirdness of the tree of life, look beyond Earth through the speculative lenses of astrobiology and face the advancement of robotics, the definition of life becomes more and more challenging.

As biologists, though, we can look at living beings and find some patterns, golden rules that any living being follows.

1) Life uses metabolism

1200px-Metabolic_Metro_Map.svg
Metabolism involves capturing external energy and transforming it into thousands of kinds of molecular structures that have multiple functions in an organisms’ body.  Image from here

In order to function, all living beings use a source of external energy that is latter transformed into molecular structures that build and power the organism. This, in a very simple way, is metabolism. Animals and fungi obtain energy by eating other organisms (plants, animals…), plants or algae obtain their power from light and water and bacteria use energy from a plethora of different sources, even including rare ones such as sulphur or iron.  

However. It is possible to have a certain metabolism without being “alive”. Metabolism is, at the end, a highly complex, multi-step chemical reaction involving organic molecules. In Oparin’s experiment, for example, simple molecules (methane, water, ammonium) were transformed into complex organic molecules only through electric discharges. This is believed to be the origin of organic molecules on Earth, and also a certain type of proto-metabolism. Similarly, multiple complex organic molecules are found in space, including polycyclic aromatic hydrocarbons, structures normally found in petroleum and tobacco, indicating that organic molecules can be formed in the absence of life.

Even living beings do not always use metabolism. Some bacteria, for example, can enter a state of cryptobiosis, in which they transform themselves into endospores, structures that remain dormant, without using any metabolism, and only become “alive”, when external conditions improve, and they restore their metabolism.

2) Life is self-replicating

agent_smiths_rev_1050_591_81_s_c1
Self replication may seem a strange sci-fi concept, but actually all life has the potential to do it! Of course, as sexual organisms we cannot make exact copies of ourselves, sadly. Image: Photogram of the movie: The Matrix  Reloaded (C) Warner Bros Pictures.

All life has genetic material (DNA) that contains the “instructions” to build, grow and operate an organism. DNA can be duplicated, and therefore, it is possible to create copies of living beings. Seeds, puppies, spores… they are all testimonies that life can self replicate. As sexual organisms, our replication involves though, a partner. So, although we cannot completely create copies of ourselves, at least half of our genes will be able to go to the next generation. We are a minority, though, and most life can just willingly self replicate, something that no rock, air molecule or drop of water could ever achieve.

However:  Crystals are structures that to a certain degree could also be said to be able to replicate. Through the process of crystallization, a crystal can grow by recruiting new atoms. These atoms are not only incorporated into the crystal’s structure, but also mirror the original crystal shape. Although this is far from self-replicating, we will see later other structures, lying between being or not alive that also show some degrees of self-replication. 

3) Life has an identity

250px-092Gastly
Life has an identity. Liquids, gases or energy have no “identity”, and therefore Pokémon like Ghastly are impossible. Image from here

Living organisms can be separated from their medium. In fact, all living beings are enclosed (minimum) into a cell membrane, a layer of lipids that separates the exterior from the interior. No living organisms is just a coherent group of molecules in a liquid or gas and sci-fi concepts such as organisms made out of energy (e.g. electrical…) do not fit in our current understanding of living beings.  

However: Some processes which are exclusively known from living organisms can also happen without an identity. Although metabolism occurs only within a cell, it happens inside a medium (water+other structures) not very different from that exterior to the cell.  The technique known as PCR , for example, allows for the formation and duplication of DNA strands in a vial without any need for a cellular structure. 

4) Life evolves

evolution
All living beings are different, show variation, and variation can be selected. With that, organisms change through time, they evolve, although the result can only be seen through long periods of time. Image from Digimon Tri.

As far as we know, all living beings evolve. Living organisms are not identical, but show variation across their individuals. Thus. some individual are able to survive better, longer and have more offspring than others, carrying those unique variations into the next generations. Slowly, variations accumulate, changing species over time; evolution. No species on Earth show no variation across its individuals and therefore, all living beings evolve. 

However: evolution is but a passive force. If there is no change in the environment, and all individuals have the same probability of surviving and reproducing, evolution may happen incredibly slowly. Multiple species (sometimes termed “living fossils”) have not experienced any major changes in their morphology or ecology for millions of years. 


These are some of the main points that can define life, although additional ones could be considered, including homeostasis (self-regulation), response to exterior stimuli… among others.  In fact, a brief search through the literature reveals a plethora of definitions for life, from chemical, to mathematical, to through the lenses of information theory! The points presented before come from the mind of a biologist, and different researchers may have different views! Additionally we should mention that this definition of life is based on common traits of creatures living on Earth, and may not be adequate to define any potential extra-terrestrial life.

Viruses and/in the definition of life

Now that we know which characteristics tie all living things, why are viruses not part of this definition?

First and foremost, we should understand how do viruses operate: 

OSC_Microbio_06_02_hiv
The life cycle of a virus (in this case HIV). Image from here

Viruses are, when not in an organism, lethargic, they do not move, feed or reproduce and are no more different than any organic molecule left on the floor (a banana peel, f.ex). It is only when a virus enters a living organism (a bacteria, animal, plant…) that starts to show some living attributes.

(1) First, the virus has to enter the cell. Viruses have protein sequences that can bind to specific receptor sites in their host’s cell. In eukaryotes, the virus hijacks the host’s defence mechanism in order to get “swallowed” and enter the cell. Alternatively, if the virus is coated in a membrane, it can fuse with the host’s (not very different from two soap bubbles merging), enabling the virus content to enter the cell. In prokaryotes, however, it is only the genetic material, which enters the cell. Overall, this is a passive process, and the virus does not generally take any action (generally). 

(2-3) The virus pours its contents into the cell. The contents include its genetic code (DNA or RNA), as well, as (in some cases) enzymatic machinery (reverse transcriptases, DNA polymerases…) that allow for the genetic code of the virus to be transformed into a DNA strand ready to be integrated into the host’s DNA.

(4-5) The host cell, while reading its DNA, also reads the virus’ DNA. The virus DNA codes not only for the proteins that will create its body, but also for copies of its genetic material as well as enzymatic machinery needed to be packed. All of these are exclusively created by the host. 

(6) All the newly produced viral materials are assembled and moved to the cells’ surface. In some cases, these assembled structures are excreted out of the cell through membrane envelopes. In most cases, though, viruses form and accumulate inside the cell, incrementing internal pressure until finally bursting out of it. 

(7) The viruses are now out of the cell, ready to infect a new host. 

Viruses do not do much by themselves. Without a host, viruses would not even be able to reproduce. This is but a simplification of their nature, though. Viruses are complex entities,  and hints of “aliveness” are spread throughout their life cycle. How do viruses dwell in the definition of life, then? Let’s take a look: 


Just by looking at the life cycle of a virus, it is clear that virus hardly follow many of the aforementioned rules to “be alive”.  However, viruses are more complex than they seem at first glance, and it is possible that many of their traits place in a blurred line between life and death. Furthermore, viruses are not the only ones in this strange place. Prions, virioids, and even artificial life, they are all participants in a race to be alive.

Stay tuned for next week, where we go through the complexity of viruses and their competitors, and we finally find the answer to Are viruses even alive? 

Thanks for reading.

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References

https://viralzone.expasy.org/

Bedau, M. A. (2003). Artificial life: organization, adaptation and complexity from the bottom up. Trends in cognitive sciences, 7(11), 505-512.

Carter, J., Saunders, V., & Saunders, V. A. (2007). Virology: principles and applications. John Wiley & Sons.

Kassanis, B. (1962). Properties and behaviour of a virus depending for its multiplication on another. Microbiology, 27(3), 477-488.

Koonin, E. V., & Starokadomskyy, P. (2016). Are viruses alive? The replicator paradigm sheds decisive light on an old but misguided question. Studies in history and philosophy of science part C: Studies in history and philosophy of biological and biomedical sciences, 59, 125-134.

Macklem, Peter T., and Andrew Seely. “Towards a definition of life.” Perspectives in Biology and Medicine 53, no. 3 (2010): 330-340.

Mougari, S., Bekliz, M., Abrahao, J., Di Pinto, F., Levasseur, A., & La Scola, B. (2019). Guarani virophage, a new sputnik-like isolate from a Brazilian Lake. Frontiers in Microbiology, 10, 1003.

Murant, A. F., & Mayo, M. A. (1982). Satellites of plant viruses. Annual Review of Phytopathology, 20(1), 49-68.

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