Teachers usually start with something that their students know, and then move onwards into the unknown. So let us start with disease.
Make lists of infectious and non-infectious diseases of humans. Kwashiorkor, stroke and scurvy are non-infectious; flu and strep throat are. Maybe have some indicator of the likelihood each kid will die of each disease in the U.S. and in the world. (TB is #1 world infectious killer, infant diarrhea is #2.)
Here is a little "starter" list:
| DISEASES | |
|---|---|
| NON-INFECTIOUS | INFECTIOUS (*=viral) |
| any of the vitamin deficiency syndromes | strep throat |
| probably most cancers | common cold* |
| most heart attacks and strokes | influenza* |
| black lung (coal, smoking) | diphtheria |
| radiation sickness | typhoid fever |
| hayfever | tuberculosis |
| genetic problems like pku, cycle-cell anemia | mumps* |
| alcohol poisoning | chickenpox* |
| trauma injury | dysentery |
| ordinary poisoning | gonorrhea |
| syphillis | |
| HIV (a cancer virus)* | |
| polio* | |
| measles* | |
Now that you've gotten them to consider that their lives may be at stake in this matter (yes, I know, kids think they will live forever - but appeal to their reason). Return to the list of infectious diseases and subdivide that into those caused by viruses and those not by viruses. They will see that most of the diseases they catch these days are viral.
How do doctors treat non-viral infectious diseases? Antibiotics usually. What about the viral diseases? There are VERY FEW chemotherapeutic agents known today, and they don't work very well. E.g.: AZT (oncoviruses such as HIV) and adamantadine (flu).
How do we hope that AZT works? Well, we have to know a bit about how viruses operate. And that opens the door onto virology for you.
Near the end you can discuss how VPHM is trying to make its "megabucks" by using a virus of a virus that cannot harm you if the second virus is not around. Since that "satellite" virus does have the machinery to get its genetic material into our human cells, what if we were to replace its genetic material with some DNA from a human? And what if that DNA were the non-mutant or "right" type - say for normal hemoglobin? That would mean that a person with cycle-cell anemia would get a dose of good genes and perhaps cure the disease. And if those "fixed" satellite viruses were to infect both egg and sperm cells, even the children of those previously sick people would be "cured".
INTRODUCTION TO VIROLOGY
Viruses MUST grow inside of rapidly metabolizing cells.
When a virus infects a cell only its genetic material plus one or two proteins get into the cell.
Simple cells that do not phagocytize require complex viruses with "injection" machinery to get their genetic material etc into the host cell. Thus viruses that infect bacteria seem to be mechanically more complex than those gooey, amorphous ones that infect - say - us humans.
Cells that can phaogocytize merely engulf the virus and take it in. Inside, the virus is unwrapped releasing the genetic material.
Viruses are like stealthy usurpers: they sneak in and change the cell into be a virus factory. This can be done by the virus's producing inhibitors that turn off some or all of the host genes, or sometimes the viruses make DNases that chew up the host's DNA.
In essence, a virally infected cell is in many ways converted to being a "virus cell" rather than a plant cell or an animal cell. The cell becomes governed by viral genes, and all the cell's original equipment now is used to make viruses. Often this kills the host cell; however, many times our human cells can abort the infection and we get well again (see next episode in this thriller).
DEFENSES AGAINST VIRAL INFECTION
The cell envelope. Viruses must attach to cells before they can inject their genetic material into the cells, or get themselves phagocytized. If the cell has the wrong sorts of envelope molecules, it cannot be infected. There are zillions of different plant and animal and fungal and bacterial viruses floating around in our environment. Most cannot attach to our human cells. Thus we don't come down with asters yellows disease, or beechtree curly leaf disease! Furthermore, in both simple (bacterial) and complex (animal, plant) hosts, there are a great many varieties of cell envelopes. Your heart cells have a different envelope than does your liver or brain or skin. Thus many viral diseases can attack only one organ or tissue.
Restriction endonucleases. (These are a type of endo-DNase that have extremely specific sequences of DNA they look for, and, when found, snip the DNA.) A host cell makes a variety of these "restrictases" - and, of course, there are no susceptible target sequences in the host's own DNA. However, if a foreign DNA comes in, it is likely - purely by chance- to possess one of those "restriction sites." Thus the cell tries to restrict its contents to having only its own DNA. The name 'restriction endonuclease' was used long before it became a tool of genetic engineering. Restrictases are probably the front line of cell's crew that inactivates viral genetic material that has penetrated into the innards of the cell.
Interferon. If a virus can attach and then get into an animal cell, and escapes the restrictases, another system comes into operation that interfers with the virus's multiplication.
Antibodies. In the case of animals from sharks upwards, the immune system makes antibodies that latch onto viruses and foul their attachment sites to that they cannot stick to susceptible cells. The problem with antibodies is that they are useful only against slow viral diseases. For the body to make enough of just the right antibody to fight a viral infection takes 3 to 5 days. (Of course, immunization by taking preventative shots works a different way - it pre-primes the body for future attack.)
Miscellaneous. It is interesting that milk and serum albumin can both inactivate large numbers of viruses. Almost no research has gone on in this regard. Probably the proteins and lipids just foul the virus's attachment gear.
PREVENTION OF VIRAL DISEASES
So far the best method known is prevention by means of vaccines. Here stories of Jenner (smallpox) and Pasteur (rabies) can be told.
However when a viral disease is actively going on and the person is sick, there is little that can be done for most viral diseases. As mentioned earlier, while many antibacterial agents (antibiotics) are known, There are very few antiviral agents: adamantadine, AZT, and a few others.
ANTI-VIRAL CHEMOTHERAPY
Thus there is a great need to develop more antiviral agents.
In order to combat viral diseases, we need to know how to kill them. Of course, we know that heat will "kill" a virus, but we'd lose the patient also! We need to find chemicals that foul the virus's workings and no anything in our normal cells. Hence, it is imperative that we know how different types of viruses attack our cells and how they make more of themselves.
We need to know what class of virus it is. Here is David Baltimore's scheme, which is based upon defining mRNA as "+":
+/- dsDNA virus
+ ssDNA virus
- ssDNA virus
+/- ds RNA virus
+ ssRNA virus
- ssRNA virus
In our cells, we need to know where the infection takes place. It could be in the cytoplasm, the nucleus, the mitochondria, or, in plants, even the chloroplasts.
PLASMIDS
When a virus gets its genetic material into a cell, one of the first things that most do is make a dsDNA circle of it. And is not just a plain circle, but rather one with a couple of extra twists in it. It is still a mystery as to why there must be no more nor no less than TWO twists. This is called a "supercoil", and is illustrated at the left:
It is from this that most of the mRNA's are made, and from this that the new copies of genetic material are made also. This is called the rfDNA (replicative form-DNA).
Interestingly, plasmids also have this form at some point in their existence. While some plasmids like to insert themselves into the chromosome as "episomes" (what's an epi-phyte or an epi-dermis?), these still have a phase in which they are by themselves in the cytoplasm - and they are circular double=helices.
How these circular helices get from cell to cell depends on whether they are viral or plasmid. If they are viral they code for extracellular packaging layers so that they can float through the environment and attach to another appropriate cell.
If it is plasmid DNA, then there are genes coding for cellular equipment that can be used in sort of a sexual way to duplicate the plasmid DNA and then send one copy through a tube into a cell that doesn't have that particular type of plasmid. Obviously, the plasmid DNA must also code for some surface components of the host cell so that other donors of this plasmid don't try to "mate" with this cell.
While most viruses make their cells "sick" or even kill them, plasmids rarely do harm to their host cells. Usually they multiply up to some small number (called the "copy number") and stop reproducing. They usually confer some sort of benefit to their hosts - new metabolic capacities, or changing the surfaces of the hosts so that fewer types of viruses can infect them.
ENVIRONMENTAL VIROLOGY
Evolutionary Leaps - Part One
In the science laboratory, usually large concentrations of viruses are employed to infect few host cells. Thus most cells get infected with 3 or more viruses.
Out in nature where individual types of viruses and their special hosts live, there are few of either. Infection is a rare event, and thus hosts usually get infected by only one virus, which has probably been waiting for a long time out there to chance upon a host. During all this time, damage occurs to the viruses. So that when an infection occurs, it might not be a "productive" infection. The host merely acquires some viral genetic material that is damaged in some critical way so that the virus cannot multiply. That damaged DNA consists of many genes - and most are probably still in working order. IF one of these just happens to have so valuable genetic property that will allow the cell to survive better, well, then the cell has benefitted - a leap in evolution of sorts.
Similarly populations of cells that contain a range of plasmids can spread those plasmid genes from cell to cell. Interestingly , the specificity of recipient is not always highly determined. A plasmid may get injected into a related species, which will then be able to evolve that plasmid into its own (getting the correct front and rear DNA sequences in place), and then might pass it on to another related species.
Thus we can see that in the Shrub of Life, there is not only lateral fusion of branches - cyanobacteria fusing with plant cells and archebacteria fusing with any eukaryotic cells, but that wafting all throughout the branches of the Shrub are viruses and plasmids that are moving small and large blocks of genes around.
JUMPING GENES! (Transposons)
Evolutionary Leaps - Part Two
We have seen how viruses and plasmids can move genes around within the branches of the Shrub of Life. But let us suppose that somewhere along this convoluted pathway by which some block of genes are moving around, it comes to a cell that contains a transposon. That transposon often can pick up a neighboring host gene and jump with it into either a plasmid or a virus genome. And that plasmid or virus containing the transposon then is moved to a new closely related cell type, where the transposon and its associated gene, jump off (damaging the viral or plasmid DNA, but nevertheless getting inserted into the new host's chromosome - conferring it with a new gene).
Whether that gene or block of genes is used immediately or not, determines the rate of this step of evolution. Most of us carry large amounts of unused DNA - just waiting for some future eon to be found useful and cause a leap in evolution.
APPLIED VIROLOGY
The BIOTECHNOLOGY INDUSTRY
Near the end you can discuss how Viropharma (VPHM), for example, is trying to make its "megabucks" by using a virus of a virus that cannot harm you if the second virus is not around. Since that "satellite" virus does have the machinery to get its genetic material into our human cells, what if we were to replace its genetic material with some DNA from a human? And what if that DNA were the non-mutant or "right" type - say for normal hemoglobin? That would mean that a person with cycle-cell anemia would get a dose of good genes and perhaps cure the disease. And if those "fixed" satellite viruses were to infect both egg and sperm cells, even the children of those previously sick people would be "cured".
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