Extreme Lifeforms: Nothing to Sneeze At
Summary (Apr 02, 2003): With more than 3500 viruses classified, a great mystery still remains as to whether they are alive at all. For examples like polio and rhinovirus, they present the only known examples of self-replication without using DNA for code storage. But with a relentless sense of survival, the kingdom of viruses can outproduce their host cells a thousand-fold while using a million times fewer bits of code.

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Extreme Lifeforms:

Nothing to Sneeze At

by Astrobiology Magazine staffwriter

Fifty years ago today in 1953, the journal Nature published a paper from Francis Crick and James Watson, entitled "Molecular Structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid". In their terse description, they drew the first double helix structure for DNA. Only a few years earlier, Watson had received his doctorate from Indiana University while working on a group of remarkable viruses that infect bacteria called the phages. At that time, great interest surrounded how they worked, and if they were alive.

The border between the stuff of life, whether molecular or biological, was about to become considerably more fuzzy.

That same year, two University of Chicago scientists, Stanley Miller and Harold Urey, demonstrated that 13 of the 21 amino acids necessary for life could be made in a glass flask. Placing water in an acidic atmosphere, sparking a lightning discharge into simple organic molecules like ammonia surprised everyone by producing some of biology's essential building blocks. Indeed the formation of life had begun to take on a distinctly molecular character, as Charles Darwin had foreseen as his classical warm pond of organic soup: (... some warm little pond, with all sorts of ammonia and phosphoric salts, light, heat, electricity etc..." ).

Holding together this tapestry of 'how a molecule becomes an organism' is one of the great mysteries still remaining in biology, and a central consideration for detecting or predicting how life might take hold elsewhere beyond Earth: Are the same viruses of the sort that James Watson first worked on fifty years ago truly 'living', or just a complex but highly efficient ordering of inanimate molecules?

The Broad Case For Life

Viruses are the smallest, simplest form of life on earth. They cannot reproduce without a host. No virus can duplicate itself outside another cell. It needs to hijack a host to survive--a true parasite in the wild.

Virus-like particles isolated from the extreme environment of Yellowstone National Park, hot springs

They are the smallest of all candidates that might define the universe of Earth's living things--if indeed they are alive at all, and if they assume the defining characteristics of all metabolizing organisms: to be self-replicating, feed, then die.

Around 1700, when the Dutch lens-maker, Antony van Leeuwenhoek, first turned the best microscopes of his time on 'snow-water', he found many 'wee animalcules' at 300 times visual magnifying power. He wrote: "The whole stuff seemed to me to be alive. But notwithstanding, the number of these animalcules was so extraordinarilly great that it would take a thousand million of some of them to make up the bulk of a coarse sand-grain."

Unlike what Leeuwenhoek first saw as animalcules, viruses are not cells, but they do nevertheless require cells. Viruses are just an assembly of nucleic acids wrapped by a protein coat (or 'capsid'). When frozen, their readiness to crystallize in highly ordered patterns was taken as a key cross-over between the purely chemical and the biological. Once crystallized, a virus can remain dormant and inert for years. But any sense that such viruses are somehow inactive or sluggish is not warranted. When matched with a compatible host cell, a single viral nucleic acid can spawn hundreds or thousands of copies of itself.

As a replicating machine, a typical virus can outproduce its living host cell by 100-fold.

So the question remains, as to whether this 'self-replication' is of any importance to the definition of life itself. Indeed in 1944 when the renowned physicist Erwin Shrödinger published his book, "What is Life?", he pointed out the central problem of how life must reproduce itself faithfully to survive. This need for inter-generational reliability can seem at first glance to be quite a challenge for such a simple and compact structure as a virus.

For instance, when compared to a computer file, the simplest of plant viruses (called viroids) contains a miniscule 240 'bits' of information to sustain their circular chromosome. By contrast, this simplicity is 10 million times less complex than the human information base (3 billion bits). Written out as a linear series of one-letter abbreviations, the code or nucleotide sequence for a single virus would take a whole page of text. The code for a human being would take five hundred thousand pages.

Century of Struggle and Discovery

The Latin name itself for virus means 'poison'. From the Far East, the global outbreak of a new pneumonia virus (severe acute respiratory syndrome, or Sars) or the African HIV epidemic are just the most current examples of what historically has devastated entire civilizations. Most notably, when European Spaniards first encountered the Amerindians, a raging smallpox epidemic decimated the indigineous culture in 1520. In the last century, the 1918 influenza A pandemic claimed between 20 and 40 million lives. Today, the names of viruses alone elicit strong visceral reactions: rabies, polio, smallpox, measles, flu, herpes, hepatitis, West Nile, and AIDS.

The collection labs have identified thousands (approx. 3500) so far.

Behind all these questions resides a large and in some cases promising body of research, including new vaccines, the global eradication of smallpox (since October 1977, after a 2000 year human scourge), and even how viral causes may be intertwined with the twentieth century's greatest killer, cancer itself.

How It Works

The basic modus operandi of a virus is to take over another organism's cellular machinery. The virus thus ties its fate intimately with the internal --and not external-- ecosystem of another species. Indeed a small virus (0.045 micron, or 45 billionths of a meter) has to hijack a big chunk of the host cell's DNA. So oversized is the match that the host DNA can be wrapped about a thousand times around the viral circumference. Its survival relies on spooling the host DNA around its outer coat like a tightly wrapped ribbon. In this way the virus is akin to the tiny mouse that spooks an elephant.

But it is the rapid evolution of this DNA packing that enables its serpentine infection to spread, since the outer coat quickly begins to resemble the host material more than its own naked protein core. This 'inside-out' innovation helps explain how viruses can claim to rule both the plant and animal kingdoms.

Viruses have another key qualification to be called 'living', if their rapid evolution and mutation are part of that criteria. Unlike any other living organism, the storage of viral genetic codes can be carried forward by RNA (ribonucleic acid), and not DNA. While not able to infect or grow without a cellular host, RNA viruses like polio and the (common-cold-causing) rhinoviruses are thus the only reproducing forms of life not employing DNA for their all important code storage.

Since the first virus was isolated one-hundred and eleven years ago (1892, by Russian Dimitrii Ivanovsky), the number of questions centering on their transmission and lifecycle seem to have ballooned: how do viruses move from host-to-host, how does the host's immune system try to check their replication, and even more simply, what do they look like? Among the two major viral classes, they are either rod-shaped or have a quasi-spherical shape termed an icosahedron. Similar to a miniature soccer ball, the icosahedron is composed of 5-sided and 6-sided faces (pentamers and hexamers). The appearance of their outer protein coat in the form of identical subunits gives them a factory-built appearance. Few other living shapes in nature have the kind of remarkable regularity of a viral encapsulate.

Computerised image of the foot-and-mouth virus, the second virus discovered after the initial Russian observations of tobacco mosaic virus. Credit: Oxford Univ.

Are Viruses Living, or Just Living With Us?

The problem with this question is how one defines life.

Viruses do seemingly have 'a plan', thus satisfying the earliest definitions for life offered by Aristotle. Viruses do furthermore offer a surprising and radical set of Darwinian choices; indeed high mutation rates are often credited with their robust survival strategies. A clean separation of viruses from the continuum of biochemistry seems unlikely. There is evidence that human DNA has many viral vestiges, thus elevating the virus kingdom to much more than some kind of biological passenger status. From generation to generation, viruses have introduced new genetic information into their victims and hosts.

The debate on defining life rarely has reached scientific consensus, despite volumes written cataloguing the various qualifications for being 'alive'. Of note however, the presence of similar molecules like DNA and RNA, even in the simplest life forms like viruses, is often suggestive of a single origin event--or at least, a whittling away of inferior encoding molecules from a multitude of less fit alternatives.

Although the only living candidate to store its key replicative information in RNA, viruses depend critically on adapting to the same code and cellular signals that govern their living hosts. Divergence into bizarre or out-of-family biochemistry would quickly prove fatal to any experiments that might widen to entirely new lifeforms, since the virus is ultimately just a parasite. That is the co-dependence of the simplest terrestrial experiment with its most complex manifestations.

The scientific community can agree on the important role that viruses have proven historically in the selection of future generations. If viruses are not alive, they certainly live with us.

What's Next

NASA's Astrobiology Institute has recently initiated a Working Group specifically devoted to studying the role of viruses and primordial life.

Of note, recent research on such diseases as foot-and-mouth disease and mad-cow disease have linked their causes to an even more primitive ancestor than a virus. The causative agent is called a prion, which lacks DNA altogether but has a virus-like coat of proteins. Prions may thus constitute the most primitive form of life, or the original common molecular ancestor of a self-replicating, feeding and dying system.

Related Web Pages

Defining Life
Life from Scratch?
Viking and the Biology Experiments
Entropy and Evolution
What is Life?
Miller-Urey Experiment: Amino Acids from Scratch
The Envelope of Life? Please



Note: Extreme Life: [2003-04-02]

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Wednesday, April 02, 2003