(From the diaries -- Plutonium Page)
With contributions by DR Tara Smith
One morning, ten years ago, I awoke in a different body. The new body looked superficially like the old. But gone was the healthy 33 year-old, and in its place was a stiff, pale wretch, aching as if I'd been beaten by sticks in my sleep, delirious from fever, with lungs wheezing like a rusty harmonica. The next day I had to be driven to the ER because, in a rare moment of clarity between waves of delirium, I realized I couldn't drive; It was that bad.
After having my vitals checked, I found myself being hustled quickly into a cardio ICU ward! The diagnosis was influenza leading to pneumonia complicated by pericarditis.
But my ordeal was nothing really: Viruses have the potential to produce a hell of lot more than a few miserable days caught in the clutches of a routine flu. In the near future, they may spell our downfall, or light a path to our salvation. A single chance mutation, a dab of knowledge, or a diabolically engineered bug, might be all that's standing between a bright future of indestructible, immortal bodies, and the grim, decaying world of Omega Man.
Primeval Earth, 4 Billion Years Ago: A toxic fog conceals a boiling sea already swarming with exotic microbes. Are early viruses present yet?
Perhaps they started out as errant bits of genetic material left adrift after the bungled replication attempt of a more complex cell. Maybe an ancient bacteria or Archaean came apart at the seams and fragments of it just wouldn't give up the ghost. Or possibly, in long vanished primeval seas simmering above countless volcanoes dotting the ocean with angry red mouths on an ancient water-world unrecognizable as Earth, there was an alien biome of RNA creatures in which viruses already thrived. They may have been with life virtually from the start in some form, or maybe they came much later. But regardless, somewhere, long ago, viruses came to be. And they've been improving their ruthless modus operandi ever since.
We arrogantly think of them as less than stupid, mindless, hapless bits of matter not even fit for the designation as a living thing. But these unassuming, quasi-organisms can bend the most complex animals on earth to their will and play us like a harp for everything we're worth. Viruses cleverly exploit all of the physiological processes we lofty metazoan creatures possess and hold dear, from the exquisite genetic machinery deep in every eukaryotic cell, to our kidneys, liver, blood, lymph glands, or brain: All of it is enlisted by a few strands of ribo-sugar peppered with nucleic acids to do their molecular bidding.
And if you think that's an overstatement of what a virus can do, just a single, sobering example: A vicious SOB by the scientific name of Lyssavirus invades the mammalian body, penetrates selected host cells and turns them into viral factories. The progeny race to the brain, activate the rage centers, inhibit fear protocols, and shut down memory and reasoning with intra-cranial swelling, while simultaneously switching the saliva glands into overdrive and flooding the liquid with hordes of virus. More viral agents lock up the esophageal muscles; swallowing becomes impossible. The end result is a furious, fearless, foaming-at-the-mouth rabid animal that bites anything that moves, thus spreading the virus to the next host via the infected saliva. The lovable family dog, the gentle tabby, even a sweet, innocent human toddler, are transformed into a mindless, snarling, real life, sci-fi zombie craving the taste of flesh, by a single speck of matter so small a million of them would fit on the head of a pin. And this brand of Lyssavirus, AKA rabies, is only one of many deadly bugs. Pretty damn impressive work for something that's not even technically alive.
Actual microscopic images of several primary types of viruses with illustrations above each: Mosaic Virus, Adenoviruses, Influenza virus, and a bacterial phage
Viruses are divided into several broad groups depending on what kind of cells they attack, how they enter the cell, how they replicate, and how they're configured genetically. One of the more interesting is the phage family on the far right which utilize bacteria as hosts. Influenza is one type of virus which attacks animal cells and is further subdivided into Types A, B, and C. Influenza Type A is the source of many flu pandemics and some of these strains are often referred to as "Avian Flu", because they can infect both birds and mammals.
Our cells really are wondrous machinations of nanotechnology. One of the more interesting processes in the millions that goes on in the sequestered realm of microbiology is mediated by little molecular runners called Messenger RNA (mRNA). Say the inside of the cell membrane needs a little repairing. In that case, mRNA go into the nucleus, pick up the recipe and a sample for making sections of new membrane, and then take the sample to the damage location and start manufacturing those sections where needed. It's a complicated process and made all the more amazing as each mRNA can carry it out several times a second. Your mRNA is humming around in there on a scale that makes a high speed Swiss Watch look both crude and boring. Viral agents such as influenza pull off a disguise using mRNA posing as the native stuff, among other deceptive processes.
The basic Type A flu looks like a spiky ovoid enclosing eight strands of instructions in the form of RNA. The latest Flu you keep hearing about is one of these and it is a real horror show. That nasty bugger is designated as H5N1; which I will henceforth refer to as "Bird Flu" in caps with the understanding that there are many strains of avian flu besides H5N1. But all these flu bugs I'm talking about going forward work more or less the same way, all belong to the same family, and they all look pretty much the same under a microscope: A little spiky ellipsoid or ball with eight strands of RNA and some other genetic material inside.
To learn more about H5N1, visit the Flu Wiki. The Flu Wiki is there for you to explore and add to your knowledge about bird flu. Click here if you are just getting started. If you want to know what your local or national authorities are planning to do to deal with an influenza pandemic, visit the national preparedness plans section (just go to your country's page).
There's a lot of ways viruses get past the outer defenses of a cell. Bacterial Phages, which look like a cross between a 'squid' out of the movie The Matrix and a miniature offshore oil rig, settle down on the bacterial surface and drill right in through the defensive exterior. But the run of the mill influenza that attacks animal cells, including the flu strain that knocked me on my ass in 1994, use a more subtle, deceptive process known by the tongue twisting polysyllabic "Receptor Mediated Endocytosis" or RME. But the bullet points aren't that difficult to follow and I promise it won't be too complicated ... because I don't understand the complex details either!
Here's a basic cell above, with a cell wall and a nucleus containing all the genes and replicative machinery needed to run that cell and reproduce when the time is right. It's minding its own business, doing its thing, perhaps this one is an endothelial cell lining a blood vessel inside the throat or nasal membrane. ... UH-OH! Here comes a marauding influenza virus! The little itty-bitty blue ball on the right, with one thing on its tiny little ... err ...mind: Making babies! (Note-not to scale)
The outside of the flu microbe has various protruding structures, or spikes. Some of these spikes are 'keys' for an existing lock on the cell's surface. The lock guards a portal that's supposed to provide entry only to those substances on the approved cellular guest list. One of many factors which affect how contagious (Or not) a given flu strain may be is how well fashioned those keys are for a given cell found in a given species. If the keys are well crafted, they pick the lock easily. Right now, Bird Flu doesn't have a very good set of 'keys' with which to pick the locks found on human cells, whereas the seasonal flu we're all susceptible to have exactly the right keys. Anyway, once it does 'dock', once it sticks a key into the lock and the key roughly fits, the cell relents, the cell wall folds in, eventually forming a little bubble encapsulating the virus called a vesicle. The vesicle then breaks off and goes merrily on its way further inward until it finds what it's looking for.
Flu virus on the surface of the cell penetrates the interior inside a bubble, called a vesicle, which eventually breaks off and travels further in. When the vesicle reaches the nuclear membrane, it opens up and delivers its deadly, viral cargo to wreak havoc on the cell
Near the nucleus the bubble opens up and the inner viral RNA strands turn into viral messenger RNA which carry a very different 'message'. Recall that legit mRNA reads and transmits instructions from the nucleus to the outer reaches in a healthy cell. The viral mRNA breaks into two enemy divisions: One sets off for the cell membrane and starts building an escape vehicle and a hatch to drive it through, the other heads deep into the nucleus to make multiple copies of the original eight strands of the inner virus. The newly minted strands then stream from the nucleus hooking up into a neat little octet as they travel to the escape hatch; the site where the other enemy division of viral mRNA has built an egress point in the membrane and a sort of body shop using the material from the membrane itself to coat the departing virus. At the escape hatch the packet of eight RNA strands is encapsulated in its viral coat, spikes and all. And the assembled virus leaves the cell for new reproductive adventures. The infected cell will keep making new viruses like this until all the genetic material is used up or the cell falls apart from the onslaught. It's pretty slick really if a little grisly ... And incidentally, I just condensed about a million gigs of information, which takes researchers half their lives studying just to get up to speed, into a few hopelessly simplistic sentences.
The problem with Bird Flu is that it's seriously virulent, with a high mortality rate. This little critter is a Flu on roids, flu with an attitude; it's packin heat. Right now, Bird Flu is limited to being transmitted from birds to people. There are only a handful of cases where the virus jumped from person to person and all involved family members of infected individuals where intimate contact increased the odds of transmission. But this state of affairs is almost certainly short-lived.
To understand why it's so frighteningly easy for a bird flu to mutate into a more contagious strain, suppose two strains of flu are attacking the same cell at the same time: Any regular old flu like the kind that goes around every year and the uber Bird Flu. These viruses are in the same family of bugs. Both contain eight RNA chains which are produced from the infected genetic material in the host cell and both form up and exit the cell in exactly the same way. Both are perfectly at home wearing the other's exterior coating. Your body defends itself by producing antibodies which bind to the flu bug and shut it down. Once the immune system has learned to manufacture a specific antibody, it 'remembers' that configuration in the event the same bug turns up in the future. That's how vaccinations work; they use a weakened or dead bug to teach the immune system what specific configuration to look out for.
What might happen in the event someone or something is infected with both strains, is a new virus emerges from the cell which is a hybrid of the two: Just by putting the strands from each virus together by mistake, just a little mix-up on the way to the escape hatch, just a little assembly required, and we have a hybrid. Lots of permutations from each strain might be tried out in that swing'n viral orgy when both strains are madly replicating away. IF one of those combos happens to combine the characteristics which make the regular flu so contagious with the Bird Flu carrying the potent wallop ... then you have an easily transmitted human flu with super-duper bird flu potency and mortality that your immune system does not recognize from its molecular memory bank! Hooray!
see link
The Type A recombinant process in pictures: At the upper right two strains of flu, "blue" and "yellow", invade the same host cell. On the left, a single hybrid emerges. For an in depth description of the process, check out the source for the pic here
This kind of mix and match process of that packet of eight strands leading to a mutation facilitating the spread of H5N1 is statistically unlikely on a case by case, cell by cell basis: But, given millions of infected cells in millions of hosts, it's inevitable given enough time. A similar process involving RNA swapping (Or point mutations, not covered in this essay) happens every year to existing humdrum influenza, which is why last year's flu shot doesn't work very well on this year's flu fashion. It only takes the existence of both types of flu in one person, or any host for that matter, in the same cell, at the same time. Sometimes this process turns existing, relatively innocuous strains, into a more lethal variant. But Bird Flu doesn't need any such luck; it's a killer already.
What would greatly increase the odds of a Bird Flu/Regular Flu hybrid forming like this would be if Bird Flu were present in a country or region with a huge population, like oh, say, Asia; and became endemic in a population of birds which have an unusually high incidence of contact with humans, such as oh, say chickens or ducks; and then a typical flu outbreak rolled around, like oh, say, they do every fall and winter: Then the odds that tons of people would have both types of flu present doing the RNA square dance, swinging their genetic partners round and round until they do-si-do a little too much and become mixed up, increases dramatically and so does this possible, dire outcome. And just for shits and grins, lets hedge our bets. Lets increase the odds further by throwing five-billion other domesticated denizens right in the same small pen with ten-billion chickens and ducks tended by 2 billion people. Lets make it an animal that is already highly susceptible to both strains.
Now we don't even need the hybrid to cook up inside a human or a bird, it'll hatch more readily inside one of Charlotte's barnyard animal friends: Wilbur could be the biological launching pad. Now that would be Some Pig!
That's why it matters if it's endemic among the commercial bird and swine populations throughout Asia. This is why it matters if an ordinary flu, one that's a little more contagious than normal, makes the autumn rounds. That's why, even if it doesn't happen this year, it's coming soon anyway, like a train on a track; all those individual elements are now in place. THAT's why some of us science geeks are so worried. Well, that and the fact that the most powerful country of all time happens to be largely under the thumb of what many consider to be the most whacked out, greedy, ruthless, incompetent set of opportunistic crooks ever. A cabal who are beholden to adoring, anti-science fundamentalist lunatics. Add in that some of said lunatics are fervently praying for the end of the world and all too happy to speed it up anyway they can, and things start looking pretty grim.
I don't want to go scaring people needlessly: But this kind of mutation is likely, some say inevitable. True, it hasn't happened yet and it may turn out we have more resistance to it than we think. And even if we don't, and even if you get sicker than shit, odds are if you're a reasonably healthy person with access to half-ass medical care to treat secondary infections and other complications, then even if you do come down with a sever case, you will probably recover in a few days. And you'll never get this specific bug again.
The danger of catastrophically massive fatalities in numbers beyond living memory is in the developing, third-world shitholes where the thronging masses do not have that kind of access to modern medical care, and may have immuno-compromised systems already due to HIV, malnutrition, or dehydration/unclean water. Or they're old or young or suffer from some other mitigating factor. If we get a flu hybrid that combines easy transmission with the virulence of H5N1, then ... yeah, it's going to kill a ton of people in those places, hundreds of millions, and there's no way in hell those nations have the resources to stop it from ripping through the population like the Grim Reaper. What then? Well since Halloween is near, lets go ahead and cut the BS and talk about a scary scenario or two. Purely in the spirit of the season you understand ...
Picture India, Pakistan, China, Taiwan, Indonesia, Latin America, with half their population sicker than hell and one in twenty dropping dead: Millions upon millions of corpses piling up. Each nation run by slightly paranoid, corrupt, in some cases senile leaders, with their finger on the nuclear button. Each convinced that the other guy purposely infected them, or at the very least didn't make much of an effort to stop the infection from spreading. A nation under that kind of assault would be too beset with their own problems to be much of an ally to the US. China's economy would contract and keep contracting for as long as it took them to get back up to speed; which could take years. They'd certainly be unable or unwilling to keep absorbing our paper IOUs in the interim. They might even have to start liquidating them. That would spell the end of massive deficit financing and, possibly, the beginning of an interest rate rise that would make the 70s look like the Golden Debt Era. And it can get worse, much worse ...
The dollar collapses, world economies unravel like cheap yarn, global currencies fail, no one can get paid; no labor for the factories and farms. Think of agriculture failing, crops rotting in the fields, domesticated animals dying by the megaton, water and electrical utilities failing; the whole global economy seizing up adding to the hysteria and desperation. Now imagine game theorists quietly informing their respective patrons that it's really safer to whack the shit out of the other country with biological, chemical, or nuclear weapons, before they get any bright ideas about going after you and your resources; or the infected, starving, pissed off refugees start streaming across your border by the millions. Throw in fundamentalist mythology based on various end of the world prophecies heavy on the pestilence and plague references, all mixed up in long standing blood feuds between preexisting enemies. Now throw in other plagues waiting in the wings: Imagine three billion people as prey, a giant pile of meat, where illnesses like Bubonic Plague, Typhus, cholera, TB, and other curses never went completely away now having that mass of humanity to feed of off. All weakened by flu, starvation, and a breakdown in basic hygiene and utilities. That my friends is definitely a worst case scenario. It's also a recipe for disaster that reaches considerably beyond a mere flu pandemic. Happy Halloween.
You might think from that gloom and doom outlook that scientists have a poor attitude towards viruses. But that's not the whole story. Viruses are indispensable in understanding biology. Endogenous Retorviruses (ERVs), a sort of genetic scar, and transposed sequences from say, dogs to cats, help clear up questions of ancestry and common descent. Some cells use what may be a domesticated army of viruses. The mRNA mentioned above, or what are called plasmids, may both be relatives of viruses which retain the ability to transpose whole genetic sequences around a cell and even swap out sections in the central genome.
In fact, plasmids, viruses, or some version thereof, probably played a critical role in larger reshuffling regimens of whole genes and entire chromosomes which eventually gave rise to a new kind of reproduction that sent evolution on a billion year trek, from one-celled critters to human beings: Sex. ... I can hear some of you prick up your ears and realize: My goodness, a world without viruses would have been horrible!
Viruses have a unique ability to sneak past cell walls, penetrate the nuclear membrane, and locate specific sequences of DNA. There they delicately snip out an unwanted segment, and/or insert a new sequences at a precise location. That's what viruses do, although they usually work against us when they're doing it. But by recruiting them to provide a benefit, disabling an unwanted gene or activating, even creating, a desirable one, we can perform nano surgery on the cell without ever breaking the membrane, much less the skin. This application, called Gene Therapy, holds a degree of promise that is almost incomprehensible in scope. We might turn off cancer cells, eliminate genetic disease after birth, or convert blue-green algae into a factory which turns sunlight and CO2 directly into gasoline, just for dreamy starters.
We're also learning to selectively breed viruses for specific tasks, and in some cases we're now experimenting with engineering them directly. (IDC fans note the term: Selection. Evolutionary biology is absolutely critical in understanding viruses in general and flu specifically. If we relied on Intelligent Design solely to manufacture flu vaccine or anti-viral drugs, create new applications for viruses, and understand how new strains develop and spread ... we wouldn't have any of that. Instead we'd all be staring at dead and dying people and animals exclaiming "Wow! Them viruses sure do look complicated").
Such designer quasi-organisms can already collect conductant such as gold or silver and deposit them as a microfine wire. The same might eventually be done with other substances under more controlled conditions, producing self assembling microcircuitry or computer chips which repair themselves. We might be able to make viruses that mine the earth for gold, iron, and other useful materials, or even asteroids. We might construct critters that thrive on deep deposits of tar and turn it into light sweet crude oil that can be pumped to the surface. In the not too distant future, we might have viruses that live only on cancer cells, designed from a cultured biopsy by a new kind of doctor; the micro-viro-oncologist, specifically for your cancer and yours alone. Now of course, all these applications could be used to manufacture some pretty vicious weaponry ...
Left: An organic nano-device of the future, engineered from a bacterial phage, sets up shop on the exterior of a human cell and prepares to go about its business. Right: A designer virus penetrates a cell to rework the genome. But are these critters delivering essential therapy or up to no good?
Living computers and bio-machines; designer bugs that eat cancer for breakfast or rebuild your entire body; nano critters combing through the crust and mantle of our planet extracting valuable items; interstellar viral armies remaking whole worlds? Or pandemics out of control; germ warfare; the subjugation of mankind to diabolical bugs that reprogram our minds to serve who knows what; finally, microbial vestiges of a forgotten conflict feasting on man and animal alike in the final twilight of our species? It's all mostly science-fiction for now, yes.
And yet it's plausible in the near future based on what we already know or can reasonably predict for these amazing devices, meticulously refined by nature, we call viruses. The parts are all already there, they have been for uncounted millennia. We've finally found the Rosetta Stone in the form of molecular biology that will translate the blueprints and teach us how to enhanced existing strains or craft new ones. The future of biotech is in our hands, good or bad. We can lay the world to waste, create a genetically engineered slave race, or deliver salvation. I'm hopeful for the latter while watchful for the worst. It's one or the other, sooner or later: It's just a matter of time, training the next generation of scientists, reading the instructions, getting to work, and some assembly required.
Epilogue: If you found this article educational, please consider going over to Aetiology, owned and operated by CO-contributor to the Panda's Thumb and The Center for Emerging Infectious Disease, Prof. Tara Smith to say howdy or thanks. Tara donated her valuable time to review my initial draft and gently offered corrections to several blunders therein. All for the benefit of Dkos Readers. In addition kudos to our own PlutoniumPage and DemFromCT for providing resources making this piece possible. Any remaining errors or omissions are solely my own.