February 04, 2008
Viruses: The Good, The Bad, And The Ugly
My January was anything but uneventful, though I rarely left my apartment. This month will be remembered by the Kleenex, always to my nose, and all the apologies, after each unguarded sneeze. My body seemed trapped in a sauna and after spending the night lying awake from a hacking cough, I found another wretched soul. Natalie Angier wrote about a New Year’s Eve visitor who “for the next 18 hours would treat the mucosal lining of our stomachs like so much pulp in a pumpkin”. Her family’s violent weight-loss program helped them lose 10 pounds, to maybe meet one of their resolutions.
Their crash-diet came thanks to a virus, a norovirus (named after a bunch of sick kids in Norwalk, Ohio in 1968). It’s more commonly called the “stomach flu” and targets the digestive system. I also had the flu, the influenza virus, which targets the lungs, not the guts. Along with the rhino and the common cold (corona viruses), January felt like a train wreck for most of us, or more aptly put, a hit-and-run.
The culprits are tiny guys, so small that thousands can sit on the period at the end of this sentence. Viruses very likely appeared about four billion years ago, though they’re are not given ‘living’ status, since they are not much more than DNA or RNA wrapped in a protective shell, without the tools for reproducing themselves or turning their genetic information into useful proteins. Viruses are fragile, entirely dependent on a host organism for survival. So they need us. And use us… whether we like it or not.
So, how do they do it? When a virus infects a host cell, the cell becomes its factory. It hijacks the cell’s machinery, turning the cell away from its usual tasks to now solely replicate the virus's genetic material and protein coat. So effectively does the virus take over the cell, with so many viral copies produced, that the cell eventually bursts under the pressure of the viral young, setting them free to infect other cells and continue the cycle.
Viruses have a kind of docking device, used to infiltrate a particular cell. Rhinoviruses dock onto receptors projecting from the cells of our nasal passages. Coxsackie virus B attaches to a surface protein called CAR, using it to invade cells in the pancreas. Hepatitis viruses are set up to infiltrate receptors on liver cells. Their specificity is from competition for a niche in a virus-packed world. As Phillip A. Sharp of the Center for Cancer Research at M.I.T. put it, “every virus has to have a scheme.”
By the way, we’re also out-numbered. Recent estimates indicate that the total number of viruses exceeds the total number of cells in every other life form - including bacteria - by a factor of ten.
Before we plan on avoiding contact with other people, and showering with chemical disinfectants there are a number of ways to fight viruses. A vaccine can prime the immune system to attack them as soon as they invade the body. If a virus manages to establish itself, a doctor may be able to prescribe a drug to slow down its spread. If all else fails, a patient may be quarantined in order to head off an epidemic.
We even have disease detectives to solve the case. They are NOT microbe detectives as I’m told by my good friend Tracy, who was a disease detective. In the early 1950s the Centers for Disease Control formed a special unit, called the Epidemic Intelligence Service, or EIS. These detectives are dispatched on two-year active assignment, paid by the CDC, in various local and state health departments, in order to combat the causes of major epidemics. Tracy tracked tuberculosis outbreaks in many regions, the last place New York City.
Some scientists are now exploring other ways to wipe out disease. Carl Zimmer wrote (NYT, 3/27/07) that they are using decoys to lure them to their death. Viruses invade a cell by latching onto certain proteins on its surface. But unlike most other cells, red blood cells can’t be infected. Since red blood cells develop in bone marrow they lose their DNA. If a virus ends up inside a red blood cell, there are no genes it can hijack to replicate itself, a dead end.
Dr. Robert W. Finberg, at the University of Massachusetts Medical School, and his colleagues, decided to do just that. They would bait their virus traps (red blood cells) with a surface protein, engineering mice to produce this protein on their red blood cells. The normal mice all died within a week of the viral infection. The engineered mice tended to live longer.
It showed some promise, but didn’t reveal exactly why they failed to eradicate the virus. Dr Paul E. Turner, an evolutionary biologist, tested what threshold was needed for these traps to force the viruses into extinction. His team mixed normal bacteria with different levels of mutant traps and then infected them with viruses. After letting the viruses replicate, they discovered there was indeed a trap threshold above which the virus population could not survive.
Scientists are using what was learned with bacteria to study HIV, the virus that causes AIDS. While now purely speculative, they hope that someday it might be possible to give HIV patients transfusions of engineered blood cells. Ultimate success would depend on the details of HIV infection. At some points in an HIV infection, a single milliliter of blood can contain as many as 10 million viruses, which would require allot of traps. It is also possible that viruses will mutate in such a way that they avoid the viral traps. The results are exciting, but still in the early stages.
Less along the lines of a ‘Viral Terminator”, but with possibly equally effective results, Dr. Paul Ewald also believes that the rules of evolutionary biology can change the course of infectious disease. http://www.theatlantic.com/issues/99feb/germs.htm
In his interview with Judith Hooper of the Atlantic Monthly, he argues that the notion of “commensalism”, which dominated medical thought for decades, is wrong. This idea was that the pathogen-host relationship inevitably evolved toward peaceful benign coexistence, because it is in the germ's interest to keep its host alive. But Dr. Ewald counters that the Darwinian struggle of people and germs is not necessarily so benign. It can go either way, toward mildness or toward virulence.
Imagine that you’re a disease organism, such as the common cold. You’d want to multiply inside your host as fast as you can. However, if you produce too many copies of yourself, you'll risk killing or immobilizing your host before you can spread. The average airborne respiratory virus would ideally want its host well enough to go to work and sneeze on people (like I did)… This is BAD.
But what if the germ doesn’t need host mobility to spread. If it can use a vector, another organism, such as a mosquito, for it to travel from person to person, it can then afford to become very harmful. That is why insect-borne diseases such as yellow fever and malaria are so horrid. Cholera uses another vector to transmit. It goes by way of fecal matter shed into the water supply... This is UGLY.
His team showed that cholera strains are virulent in Guatemala, where the water is bad, and mild in Chile, where water quality is good. Moreover, strains of the cholera agent found in Texas produced such small amounts of toxin that rarely anyone who gets infected will come down with cholera. On this, he said, “If you can make an organism very mild, it works like a natural vaccine against the virulent strains. That's the most preventive of preventive medicine: when you can change the organism so it doesn't make you sick."
Dr. Ewald has also taken the laws of evolutionary theory, and applying them to a new theory: that diseases believed to be caused by genetic or environmental factors, such as certain forms of heart disease, cancer, and mental illness, are in many cases actually caused by infections. The ordinary stomach ulcer is the best recent example of a common ailment for which an infectious agent turns out to be responsible.
The medical establishment had earlier thought that peptic ulcers were caused by: environmental factors, smoking, diet, certain drugs such as aspirin, or stress. Not infection. So for years, ulcer patients ate bland food and swore off stress. But in 1984, Marshal and Warren indicated that maybe an infection explained the ulcers. It was ignored, until Marshall reportedly “personally ingested a batch of the spiral bacteria and came down with painful gastritis”. There is now little doubt that Helicobacter pylori causes inflammation of the stomach lining. 20% of those infected produce an ulcer. Many can be cured in less than a month with antibiotics.
Ewald takes Darwin’s laws to mean the evolutionary success of an organism relative to competing organisms. Genetic traits that may be unfavorable to an organism's survival or reproduction do not persist in the gene pool for very long. Natural selection, by its very definition, weeds them out in short order. By this logic, the genes that spell out that disease or trait will be passed on to fewer and fewer individuals in future generations. Therefore, in considering common illnesses are unlikely to have a genetic cause. He says "When diseases have been present in human populations for many generations and still have a substantial negative impact on people's fitness, "they are likely to have infectious causes." This may offer a new way to think about the causes of our most baffling illnesses, that we have previously considered tied to genetic or environmental factors.
With news about AIDS, Ebola, the Avian Flu and SARs, it’s hard to imagine anything good could come out of the viral world. But while viruses are the pirates of the cellular sea, there may be a few Peter Pans also around. Scientists are starting discover the extent of viral diversity, which may one day radically shift how we think of our uninvited guests.
Hamish Clarke wrote that viruses, which are cheap, quick to produce, and easy to modify, “filled out the toolboxes of many a biologist” for years. Martha Chase and Alfred Hershey used viruses in 1952 to help establish that DNA, rather than protein, forms the basis of heredity. Their success launched its new career. Their ability to entwine themselves with the host's genome has made viruses an important factor in the field of gene therapy. The notion of going into a person's cells and correcting genetic 'typos' earlier seemed unlikely. But now researchers are planning to swap the virus' harmful genes for a corrected version of the patient's defective genes and use the virus' unique abilities to insert the gene into patient's genome. Like a Hollywood movie, the scientists are essentially hijacking the hijackers.
Patients may feel uncomfortable with the thought of being injected with a virus to cure a disease. But, according to Paul Osten, from Northwestern University in Chicago, the risks are low and decreasing. He wrote that "The viral vectors … are in most cases stripped down to the most basic elements that are required for gene delivery, and thus in no possible way pose any risk with respect to the original disease."
We always hear about their assault on humans, but viruses don't just attack animal cells. A large number of viruses actually target bacteria, including the bacteria, called bacteriophages (phages for short), that infect humans. Targeted bacterial killing may be an alternative to antibiotics. Sounds like another Hollywood thriller, but it’s very real. In August of 2006, the U.S. Food and Drug Administration (FDA) approved a bacteriophage food spray designed to reduce the amount of illness-causing bacteria on ready-to-eat meals.
Viruses were known to do allot to control other parasites. But they are now recognized to be an integral part of every ecosystem and can't be ignored. Microbiologist Nick Colman said "We usually only hear about viruses in the context of human disease. But most viruses are actually not harmful, and in fact have played an important part in evolution and in maintaining healthy ecosystems." Andrew Holmes, a microbiologist from the University of Sydney, thinks that people should know that viruses “have the potential to cause very rapid biological change through epidemic disease, but that is exceedingly rare”. He pointed out that this same process is an important part of correcting imbalances that occur in nature, such as explosions of algae that choke sea life and disrupt food chains. He notes that, "such viruses are the means by which the ecosystem corrects itself."
It's now February, and my nose still runs and my head feels like a football. Still my role as reluctant host has become little more clear, and my thoughts for these uninvited guests a little more understanding (though I still dont want them around.
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