THE BONUS ROUND PRESENTSDickie's Personal HIV Theory.
The FULL MONTY - Chapter 2
by Dick Remley, every doctor's nightmare:
A PATIENT WITH AN INFORMED OPINION
THE FULL MONTY
CHAPTER TWO: THE EXPERIMENT
Remember how I've been promising you that this stuff is going to get real technical eventually? Well, this is the last chapter in which I am NOT going to get all that fancy. In the chapter following this one, I'm going to get as technical as I both need to be and know how to be. So, listen up:
First, let's recap where we are at:
According to the CAT (Currently Accepted Theories), HIV disease is caused by the HIV virus producing gazillions of viral offspring that gradually overwhelm the immune system by killing off T-cells. The slow decline to AIDS is explained by the body's apparent inability to replace the T-cells as quickly as they are destroyed.
The problem I have with that idea is that it appears to be describing a delicate state of equilibrium that is reached between the virus and the human body. Yet, as we have observed, that state of equilibrium seems extremely difficult to perturb. Very significant increases in viral load during illnesses don't seem to tip the scale in favor of the virus. Similarly, decreases in viral load don't seem to give the body much of an edge, either, unless the viral load is reduced to almost negligible amounts.
Most attempts to explain these phenomena do so in a vacuum. That is to say, they advance an explanation in one part of the CAT that contradicts another part of it. If declines in T-cell counts are caused by the rapid kill-off of T-cells by the virus, then disease progression ought to be rapid in most cases - and it is not. If the slow decline in T-cell counts is accounted for by rapid T-cell replacement, then giving the body even a slight edge ought to allow the body to overcome the disease - and it does not. How can it be that, in the vast majority of cases, T-cell replacement and the decline in T-cell counts reach some state of equilibrium? Given the wide range of viral load counts that patients exhibit, shouldn't that be the exception, rather than the rule?
There appears to be something wrong with the CAT. (Furballs, perhaps?)
All sorts of elaborate schemes have been advanced to explain these apparent difficulties. Elaborate schemes in science make me nervous. Fairly predictive models to describe the motions of the planets with the Earth as the center of the universe were advanced many centuries ago. The tip-off that these models were incorrect is that they all relied on very elaborate mechanisms. The answer, of course, turned out to be relatively simple: the Earth is not the center of the solar system - the sun is.
Not that elaborate explanations can NEVER be right - they just tend to make me nervous.
The THEORY, however, advances a relatively simple explanation: Dead T-cells are replaced. Absorbed T-cells are not.
Now, it is possible that the replacement of dead T-cells requires a complex bodily mechanism akin to taking a physical inventory. (I can sense many of you in the retail trade shuddering already.) However, it is well known that the cells of the human immune system use a biochemical process to communicate with one another, and with the body as a whole. Certain chemicals are released by cells at the sites of infection. These chemicals are various in number, and can turn the inflammatory response on, stimulate production of other cells, etc. They are generally known as "cytokines" (which means "that which moves between cells" ). Some examples of cytokines are: Tumor Necrosis Factor (TNF), the Interleukins ( IL-1, IL-2, IL-12, etc.) and the Interferons. Since cytokines present a known biological model for cellular production and communication, why bother to introduce complex mechanisms until we've checked out the obvious one?
As far as I know, no cytokine that performs the signaling function that The THEORY requires has yet been identified. But does it even exist? Could we attempt to prove its existence experimentally? What form might such an experiment take?
Well, I have some ideas about that. (What, you thought I wouldn't?)
If dead T-cells are required to stimulate production of new T-cells, then why not introduce a lot of dead T-cells into an HIV-infected individual's bloodstream and see what happens? Now you could try to do this by killing off a person's T-cells while they are still inside his body, but there is a real danger of complications arising out of this method. Besides, just try and suggest the attempting of such a procedure to a doctor. I have. They tend to either run from the room screaming, or subtly ask you if anyone has ever suggested that you might like to try some anti-psychotic medication. I'm exaggerating, of course; but they REALLY don't want to do that. And not without legitimate concerns.
However, there is another way:
Over a period of time, draw a supply of blood from an HIV-infected patient who has relatively low CD-4 counts. Draw a sufficient quantity of blood to roughly equal the volume of blood in his body. (This is the reason for drawing the blood over a period of time.) Store the blood until you have about the right amount. Separate out the CD-4 cells. (There are existing techniques for doing this.) Or, separate out the CD-4 cells BEFORE storage. It shouldn't really matter because of the next step: Kill the CD-4 cells. Infuse them back into the patient.
If the number of LIVE CD-4 cells in the patient rises to about double what he started with - congratulations!: you've demonstrated a connection!
It doesn't sound that difficult to me. Nor particularly expensive by scientific research standards. And, it has the added benefit of not requiring that the mechanism for any T-cell increase be known, whether it is complex or not. It simply proves that such a mechanism exists.
Now, I don't do this sort of thing for a living, so I don't really know all the practical details, but I'm going to suggest the one problem I can imagine, and leave the rest open for discussion by someone who knows about these things.
The problem could involve a possible inflammatory response. What if the cytokines in the cells induce a massive inflammatory cascade? (As if your body thought all your blood was being destroyed and had a violent response to it.) It could get ugly. Or worse.
However, this fear might be unfounded. As I said, I just don't know. I suppose this question could be answered by experimenting first on animal models (such as SCID mice) and adjusting the rate of infusion, if necessary; although that would significantly increase the cost of the experiment. I'd personally be willing to volunteer in place of the animals, though.
Now some issues involving the details:
The reason for using the patient's own blood instead of blood from donors is that we don't really know what the mechanism is, if it exists. The process could turn out to be host specific (meaning that the exact chemicals involved are unique from person to person, and might not be transferable to another patient). Using the patient's own blood avoids the problem of having to confront this issue later, if the results are negative.
The reason for using such a large quantity of blood from a patient with a relatively low CD-4 count, is that you want the result to be definitive. You don't want to get a modest increase in a relatively normal patient. That could give rise to the argument that an affirmative result was just a matter of chance. If we're going to do this thing, let's at least try to do it right.
In killing off the CD-4's in the blood drawn, the method chosen to kill them must be one that doesn't also destroy a potential chemical messenger. (This chemical would almost certainly be peptide-based.) It is a little beyond the scope of my knowledge to be able to say which would be the best method of accomplishing this. It would be very simple and inexpensive, at any rate. You just don't want to reduce the cells to an incomprehensible slag of simple atoms.
The rest of the details are pretty easy to figure out: you'd want to check the patient's baseline CD-4 count as close to the time of the infusion as possible; you'd probably want to do multiple, frequent CD-4 counts on the patient prior to the experiment to check for natural variability of results; etc. That sort of thing ought to be fairly standard experimental procedure.
I'm going to spend the rest of this dissertation explaining the details of HOW I think the process described in The THEORY might be taking place, rather than WHY I think it might be happening. So, in the next chapter, I'm going to embarrass myself by attempting to explain these processes in a very technical way.
But, you might want to stay tuned... because I am also going to go way out on a limb and tell you exactly WHERE in the cell I think we should look for this mysterious chemical "messenger".
A DISCLAIMER FROM STEVE SCHALCHLIN: Dickie is my friend in Los Angeles who was infected with HIV in 1981. He's been through more near death experiences than anyone I know, including a recent two month delirium where his liver was failing and he was dying. But through a careful balance of some drugs that alternatively dehydrate and then rehydrate him, he is alive yet again.
Dickie, after he got sick, began reading books on microbiology. And when we met earlier this year, he used to sit for hours and just explain for me microbiology and all the sites on the cells and what proteins do, etc. He kept telling me about his theory about the immune system. He had it well thought out and, as far as he could tell, it -- THE THEORY -- can account for all the phenomena that has occurred so far in the strange tale of HIV.
This does not mean he is right. His theory is untested. It is ONLY theory. It came to him as he read book after book on microbiology, so it could be a naive theory or it could be one of a billion theories. So why have I invited him to be a Bonus Round site?
Because when he's hot on the trail of new information and when ideas are popping in his head; when he's making new discoveries through the books and published studies, I see him come back to life the same way Jimmy saw my songs bringing me back to life.
There are scientists who read my page, you know. Even if his theory doesn't pan out, I will learn a lot about my own body and about the thing that almost killed me. (cue song: "at least i know what's killing me").
Dickie is not a doctor nor does he work in the medical field.
He's a Patient. *cue the mannix theme*
So, the reader should note that THIS IS ONLY A THEORY we are using as a jumping off point to ask questions and learn more about HIV and the immune system.
WE ARE NOT SUGGESTING ANY PATIENT TRY ANY METHOD OF TREATMENT WHICH MIGHT BE SUGGESTED OR INFERRED. WE ARE NOT RESPONSIBLE FOR YOU IF YOU DO SOMETHING STUPID -- LIKE TRY ANY TREATMENT WITHOUT THE FULL CONSENT OF A LICENSED MEDICAL DOCTOR.
Tell us what you think. -- The Bonus Round Management. :-)
© 1998 by Richard Remley
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