13 Things That Don't Make Sense (15 page)

That paper forcefully ushered in the age of the archaea as sitting alongside bacteria and eukaryotes like you and me. And
that little parenthesized
at least
left the door open for more. Perhaps there are four branches, not three. Enter, Mimivirus—if it dare.

Despite Woese’s calls for open-mindedness into the future, Mimivirus has not been welcomed with open arms. A virus that threatens
to redraw the biological landscape again was never going to have an easy ride. And so far it hasn’t. The jury is still out
on whether Mimivirus should even be accepted as a form of life. This hedging seems extraordinary when Mimivirus is genetically
more complex than some bacteria—all of which are considered to be alive. Why shouldn’t Mimivirus be welcomed as a member of
life’s club? The only answer seems to be “because it is a virus.” The orthodoxy says that viruses are parasites. Which means,
logically, they can’t have existed until after some other life-forms came into existence.

Logic is a wicked thing, though; it often relies on subtle assumptions. What if, for instance, viruses weren’t always parasites?
What if they evolved before life split into eukaryotes, bacteria, and archaea, but subsequently lost some of their independence?
In that case they would have every right to be called alive—and they might hold clues, as many clues as the other three groups,
about our
Last Universal Common Ancestor
(
LUCA
). Since LUCA is practically the holy grail of biology, it doesn’t do to ignore the possibility, and the claim is not without
foundation. Around half of Mimivirus’s genes are unknown to science; no one has a clue what they encode. Considering how many
genomes we have now sequenced, how many genes we have seen, that is rather surprising. Unless, that is, Mimivirus really is
from another age. So perhaps in a bygone era Mimivirus wasn’t a virus at all, but an independent, free-living organism that
later fell on hard times and resorted to piracy. The 450 hitherto-unseen genes are one hint toward this; they may be relics
of the distant past. But it is the seven genes it shares with every other living thing that provide the most intriguing clue.

Sequence your genome, and you’ll find all kinds of interesting things. But among the genes that make you you, you’ll also
find sixty or so genes—the
universal core genome
—that link you to all of Earth’s life. There are copies of these genes inside every biological cell on the planet, copies
that write a textbook of the history of life on Earth.

We know this because genes, which are arrangements of acid molecules, are littered with mistakes: places where the acids have
been linked up in the wrong order, or where something is missing altogether. This happens occasionally during the construction
of a new copy; DNA is good at replicating itself, but it’s not always perfect. Radiation can also cause mutations. Whatever
the cause, the result is only occasionally disastrous; for the most part, the organism survives without any problem. These
mutations then get passed down the generations and provide a hereditary characteristic. Just as it is possible to use certain
physical attributes—a peculiarly beaked nose, for example—to pick out who is related to whom at a wedding, scientists can
use the genetic mutations to work out the family relations in a group of organisms. If two of them have the same mutations
in their core genes, they will have a common ancestry. By comparing all the various mutations, we are able to place organisms
on an evolutionary tree.

Since Mimivirus has seven of these genes, Jean-Michel Claverie, another of the Marseille researchers, was able to compare
its mutations with the known mutations in the rest of the living world and find its place on the tree. And it was rather a
shocking discovery.

The team’s 2003
Science
paper had shown that analysis of the giant virus’s proteins placed Mimivirus as a “deep branch” in the classification tree
for the NCLDV viruses and left it at that. Less than two years later, they published the follow-up, again in
Science
, and this time they came out all guns blazing. The 2003 paper had taken just one page. Their November 2004 paper was seven
pages long; Mimivirus was proving to be a gold mine. The complexity of its genome means that Mimivirus “significantly challenges
our vision of viruses,” the researchers wrote. They backed up their argument by referring to a 1998 paper that suggested a
line of DNA viruses could have emerged before the three accepted domains of life split. The tree of life, they suggested,
ought now to be redrawn.

Mimivirus, according to Claverie, occupies an entirely new branch, right down near the base of the tree. Its mutations suggest
it evolved before the eukaryotes and their complex, structured cells—the very things it now infects. Most controversially
of all, Mimivirus may even be directly responsible for the development of the well-organized cells that make you what you
are.

BIOLOGICALLY
speaking, we eukaryote organisms are very impressive. Our cells have complex structure; somewhere along the evolutionary line
the scraggy mess of the primordial cell turned into something with neat compartments and a nucleus that kept all our genetic
information in one tidy package. The thing is, nobody knows how a cell first equipped itself with the extraordinary innovation
that is a nucleus.

It was Franz Bauer, a celebrated biological artist (officially, “Botanick Painter to His Majesty”), who first described the
nucleus in 1802, but in 1831 Robert Brown, the Scot who first observed Brownian motion, gave it the name that stuck. Since
that time, biologists have come to appreciate just how astonishing the cell nucleus is; the complexity of its structure is
matched only by the complexity of the tasks it carries out. Its DNA replication mechanisms, which create cellular life with
consummate skill and ease, are the envy of every synthetic biologist.

The biologists do have a few ideas about how such a beautiful thing could have evolved. One respected possibility is that
a merger between bacteria and archaea could have led to the formation of a nucleus; an archaeum trapped inside a bacterium
provides the right kinds of conditions. This is fine, except that we also have evidence that cells with something like nuclei
evolved before bacteria and archaea.

There are various other options; biologists can meet up and discuss them endlessly. It’s just that they seem unable to decide
which one is right. One of the few things they
can
decide on, though, is which, among all the options, is the long shot, the far-fetched idea that is allowed into the meeting
only if it displays a badge marked
controversial
. Which idea is this? The virus, of course.

The champion for the virus idea for the origin of the nucleus is a Sydney-based microbiologist called Philip Bell. In 2001
Bell came up with a rather surprising hypothesis. What if a virus infected one of the scraggy, disorganized prokaryote cells
and did something unexpected? What if, instead of just using the cell’s molecular machinery to replicate itself and then move
on, the virus actually took the reins? This new axis of evil, something somewhere between a bacterium and a virus, would have
had abilities nothing else could match. And so, in evolutionary terms, it would have had a promising future. It would be able
to engulf other organisms that had to make do with simple chemicals as food. Once it had engulfed them, the viral apparatus
could simply take exactly what it needed from them.

There is circumstantial evidence that a virus—specifically, a DNA virus, Bell believes—could have been the first nucleus.
Both are packaged DNA encased in a protein coating. In some relatively simple organisms, such as red algae, the nucleus can
move between cells in a way that seems to reflect viral infection. Both package their DNA in linear chromosomes, while bacterial
chromosomes are circular. The viral DNA strands even have primitive forms of
telomeres
, protective buffer zones at the end of the chromosome that are present in eukaryote chromosomes. (Their loss is thought to
be linked to the process of aging—providing a link between viruses and the anomaly known as death, which we will explore in
the next chapter.)

There are more similarities, but none is a smoking gun. Nevertheless, Bell has repeatedly stated that a DNA virus infecting
a primitive archaeum could lead to something like a eukaryotic nucleus. The only flaw in that argument has always been that
viruses are so unimpressive, so small, and so genetically uncomplicated. We know that cell nuclei are complex and impressive—how
could a virus produce something like that?

For ten years, Bell searched for a virus that would be up to the task of becoming a nucleus. With the discovery of Mimivirus,
he thinks he’s found it; Mimivirus, he says, is the missing link. It’s still a highly controversial view, however, because
viruses have just not made it into the mainstream of evolutionary thinking. They were never considered alive, so how could
they be part of the story of life? After all, viruses need something to host them, something to piggyback on. They are just
replicons
, bags of chemicals whose only purpose is to replicate themselves. And so the debate goes on. For the moment, for most biologists,
Mimivirus remains an intriguing anomaly but nothing more.

A few biologists, though, insist their colleagues are in denial. Luis Villarreal, the director of the University of California,
Irvine’s Center for Virus Research, for example, sees viruses as “the world’s leading source of genetic innovation” and thinks
they are most probably the root of life on Earth. Much of the human genome, he points out, is viral in origin, so it is not
a big stretch to imagine that LUCA, our Last Universal Common Ancestor, was some kind of virus.

The discovery of Mimivirus, with all its unexpected, unviral properties, has only served to cement Villarreal’s view, and
we have only just scratched the surface; there are probably plenty more giant viruses out there. In the last few years Craig
Venter, the human genome pioneer, has been going back to life’s roots, sailing the Earth’s oceans, sampling the water every
couple of hundred miles, and then sequencing the DNA in the bucket. Circumnavigating the globe in a one-hundred-foot boat
called
Sorcerer II
is a wild way to do biology, and it has produced suitably stunning results. In the Sargasso Sea off Bermuda, Venter’s team
found more than eighteen hundred new species and more than 1.2 million new genes; so far, the trip has given us a tenfold
hike in the number of known genes. And every bucketful of seawater—if you can call a two-hundred-liter container a bucket—contained
millions of viruses never before seen by humans.

AS
we have already hinted, the importance of getting to grips with viruses, rather than ignoring them, goes further than an abstract
understanding of the tree of life. Viruses in general, and Mimivirus in particular, may hold the key to longer life, a key
that seems rooted in their power to infect and commandeer a cell’s machinery.

After Mimi was first identified in the Marseille laboratory, the researchers carried out various tests to determine the kinds
of organisms it would infect. They ruled out human beings. Wrongly, it turns out. In fact, it is likely that a good many of
us have antibodies to Mimivirus in our immune systems. When a research team in Canada examined a few hundred pneumonia patients,
around 10 percent of them had antibodies to the virus; Mimivirus—or something like it—certainly used to infect humans. We
already knew that many human incidences of pneumonia are due to unidentified microbes, and a study in France had shown that
injecting mice with Mimivirus resulted in something like pneumonia. The final answer came when a technician in the Marseille
lab came down with a fairly ordinary bout of pneumonia in December 2004. He was given a standard blood screening, which showed
he had become infected with Mimivirus. The Marseille lab now operates with a slightly higher level of safety procedures,
known officially as Biosafety Level 2.

Infection by viruses is almost universally seen as a problem. However, there are cases where it is potentially lifesaving.
In 1988 Patrick Lee, then a professor on the medical faculty of the University of Calgary, announced in
Science
that a virus that is relatively harmless to humans can kill cancer cells. It is called a
reovirus
, and it seems to be drawn to cells showing abnormalities in a cell growth–regulating gene called
Ras
. Since most cancer cells have mutated Ras genes, it seems a plausible mechanism for fighting cancer without damaging normal
cells.

Reovirus is currently being tested in clinical trials. The list of cancer cells it will kill is impressive—cancers of the
breast, prostate, colon, ovary, and brain, and lymphoma and melanoma—but its power is not yet fully proven, and Lee and his
colleagues are having to work hard to identify exactly what biological processes are involved in the viral action and reaction.
The interesting thing is, the wider fight against cancer, an attempt to understand exactly the same issues, is now becoming
closely linked with the fight against aging—and that is, in turn, causing us to reassess our understanding of just how eukaryote
cells work. The prokaryotes don’t age, so researchers are now going back to studying the detailed differences between eukaryotes
and prokaryotes—which means revisiting the time when the tree of life started to branch. Since viruses like Mimi are now intimately
involved in the debate over this era, it is just possible that Mimivirus has a deeper significance than anyone ever imagined.
The origin of aging and death is linked to the emergence of the eukaryotes. And so is Mimivirus—especially if it really was,
as a growing number of researchers now believe, the origin of the cell nucleus, the defining trait of the eukaryote cell.
If there is a possibility that viruses can selectively infect and kill cancer cells, as Patrick Lee’s initial findings show,
perhaps that is because they go back to a time before the emergence of organisms whose cellular mechanisms go awry and cause
them to age and die. It’s an interesting speculation. However, as we will see in the next chapter, the possible role of a
giant virus is just a small part of the anomaly we know as death.