THE BONUS ROUND PRESENTS
Part Three: Dickie's Personal HIV Theory.
The DIME Tourby Dick Remley, every doctor's nightmare:
A PATIENT WITH AN INFORMED OPINION
PART THREE: THE DIME TOUR So, okay: you've read The Nickel Tour and you're still not bored, but you may have a few questions.
First of all: if HIV is not really successfully infecting a lot of new cells all the time, what accounts for the decline in the number of T-cells?
T-CELL DEPLETION - PART ONE: APOPTOSIS
(Uh-oh...Big Words Already)You can SEE T-cells die off. This MUST disprove the principle of The THEORY, right? Well, not necessarily. Remember that the basic principle of The THEORY is that none of the participants (you, your cells or HIV) are doing anything WRONG. All organisms involved are just trying to do the best they can. HIV doesn't know YOU exist. It is simply utilizing the available resources (your cells) the best way it can.
From a Darwinian point of view, this would almost HAVE to happen sooner or later... the virus that does the best job of utilizing resources would have a survival advantage over varieties that do not accomplish that.
HIV reproduces rapidly and in vast numbers. And it makes a lot of mistakes when it replicates. Hence, it mutates very rapidly. This allows it to quickly select for variations that are better adapted to the environment in which it finds itself. A "hungry" virus that eats up every cell around would rapidly run out of its "food" supply. But one that invaded a cell and kept it alive as long as possible would live to produce more offspring like itself, and hence would have a survival advantage.
*THEORY: HIV is really trying to keep the infected cells ALIVE, not kill them.
Okay, so all that makes sense. But you can still SEE T-cells die off. How would The THEORY explain that? Well, remember that your body's CELLS are also doing their best to survive. What makes them different from the HIV virus is that the cells in your body have evolved over millions of years into a life form that lives in colonies. Your body's cells each have a highly specialized function, and require the support of other cells in the colony (a.k.a.: your body) to perform other functions.
In other words: each cell of your body does its own special part to work TOGETHER with others to assure the survival of the whole colony. (Unlike many people, it seems.) When a cell becomes infected, it communicates to the rest of the body that it is "sick". If the other cells of your body can't save the infected cell fast enough, it may "commit suicide" in order to protect the surrounding cells from infection. (Very romantic, eh?) Cellular suicide ("programmed" cell death) is referred to as "apoptosis".
Now the picture begins to come together a bit:
*THEORY: T-cell death in newly infected cells occurs through apoptosis.
Once the HIV virus enters a cell, it would have to move rapidly in order to save the very life of the cell it has infected before the cell "calls for help" and commits suicide. The result is a biological race against time. I assert that this is a race that HIV often loses. In an ironic sense, this would imply that a certain amount of T-cell death might actually be a "good" thing.
Now, from an evolutionary standpoint, this makes perfect sense. HIV would likely have evolved rapidly into a form that keeps the cell alive as long as possible. And your body's cells have evolved to cooperate with other cells in order to preserve the whole organism (namely: YOU) - even to the point of suicide.
The result is an ironic evolutionary twist: to the outside observer, it would be natural to assume that the virus is trying to kill the cell, and that the cell is trying to survive; when, in fact, the virus is trying to SAVE the cell, and the cell is trying to destroy itself. This seems to me to be so likely as to be probable, rather than possible.
But what's the big deal? One way or the other, HIV is causing cell death. We've really just described a mechanism for T-cell depletion that would seem to support currently accepted theories rather than The THEORY, haven't we?
Well, I'm not done yet. Don't be so impatient.
Cells in your body die all the time, and have to be replaced. But if your body just replaced cells on a simple "time clock" basis, producing new cells at a regular pace, you'd end up with either too many or too few cells almost all the time, due to errors and delays in synchronizing the timing.
*THEORY: Cells must somehow signal the body when they die, so that they can be replaced.
If this is true (and there is a large body of scientific evidence that cells do send out chemical signals), then dying infected cells would be replaced by healthy new ones at about the same rate as they die off.
The expected consequence of this would be that T-cell counts would remain at a certain relatively constant level for a very long time, despite the presence of HIV infection. This is a known fact. The average time from infection to death (in the absence of treatment) is about eleven YEARS. Critical decline in numbers of T-cells doesn't really occur until about the last three years of the illness.
But T-cell depletion DOES occur slowly, and then suddenly accelerates. How does The THEORY explain that?
T-CELL DEPLETION - PART TWO: SYNCYTIA
"Syncytia" is a fancy word used to describe cells infected by viruses (including measles, cytomegalovirus, and HIV) that can cause the infected cells to be able to absorb other cells.
Now, you will often see syncytia described as "cell clumps" or "cell clusters". This conjures up images of cells gathered together like bunches of grapes. But, if you ever see pictures of syncytia, what you see appears to be much more like one big cell with a whole bunch of nuclei.
So, why is this important?
Remember that The THEORY requires that HIV must have a mechanism for keeping a cell alive.
*THEORY: By ABSORBING rather than killing other cells, the virus incorporates the nutrients and mechanics of the absorbed cell into the infected cell, thereby increasing the pool of resources available to the virus.
Think of it like going out and buying a second car, and using the parts from it to repair your first car. The more cars you buy, the more parts you have to keep the original car running.
What would be the consequences of such a mechanism to the human body as a whole?
Well, remember that we have theorized that dead T-cells would signal the body to replace them.
BUT: if the cells are absorbed rather than killed, then there are no dead cells to send the replacement signal. Absorbed cells would not be replaced. Over time, the population of individual cells would decline in number.
However, we don't really see a large number of syncytia until the late stages of the disease. The percentage of syncytial HIV-infected cells in the bloodstream appears to be fairly low until the later stages of infection. So, if we don't see them in the bloodstream, where are they?
T-CELL DEPLETION - PART THREE:
HIV MEETS TV-LAND: "MY LITTLE MARGINATION"Giant syncytial cells don't work as well as normally sized cells.
It is one of the functions of white blood cells (of which T-cells are a part) to be able to squeeze through the walls of capillaries and such in order to be able to reach sites of infection and inflammation. A giant cell just wouldn't be able to squeeze through the membranes very well. In fact, as it grew in size, a syncytial cell (more properly called a "syncytium") would approach the point at which it couldn't squeeze through at all. But, before that, it would likely reach a point where it would be able to squeeze partway through, and then get stuck.
The process by which blood cells get stuck in surrounding tissues and therefore no longer circulate through the bloodstream is called "margination".
I will use the term "margination" in a somewhat broad sense in this section. When I use the term here, I mean it to refer to any process by which blood cells cease to circulate and become stuck to or imbedded in surrounding tissues. Some white cells and T-cells might do this by a process different from the one described above.
*THEORY: HIV infected cells that have become syncytia marginate into surrounding tissues and get "caught".
Margination can cause inflammation of the tissue in which the cells are caught. The function of white cells is to migrate to sites of infection and inflammation in order to control disease processes. Inflammation attracts white cells. An HIV-infected syncytium absorbs other white cells, becoming larger. Larger cells would tend to marginate.
Hmm... notice a pattern here? Now we can see a kind of process at work:
HIV would cause a successfully infected cell to absorb other cells. At first, this would hinder movement of the HIV syncytium only slightly, and the cell would be less functional, so its chances of coming into direct contact with another T-cell is only just so-so, and disease progression is slow.
But, over time, the infected cell would gradually grow in size until it marginated, causing inflammation and attracting other T-cells to it. After a certain critical point is reached, disease progression would become rapid. Kind of like a dying star in space growing in mass continually: eventually it forms a "black hole", and everything nearby gets sucked into it. The cells getting absorbed into an HIV syncytial "black hole" would never be replaced, and the immune system would collapse.
SUMMARY
Congratulations! You made it to the point where we can now summarize the basic concepts, and put the whole THEORY together for the first time! (That really wasn't so bad, was it?)
If you will notice, throughout THE DIME TOUR, we have encountered certain "bullet points" marked by the word "*THEORY" in capital letters. If we pull all these concepts together, along with a basic concept or two presented in THE NICKEL TOUR, we should get a summary of The THEORY in simplified form:
THE THEORY
HIV is trying to keep cells ALIVE - not kill them.
HIV does not really move very well from one cell to another through the bloodstream, and must produce a vast number of offspring in an attempt to accomplish that task.
Once the human body mounts a defense against HIV, the virus's ability to move from cell to cell is even more severely curtailed.
Many of the newly infected cells will kill themselves through apoptosis.
The T-cells that die signal the body to produce more T-cells to replace them.
Cells that have been successfully infected by HIV become syncytia and absorb other cells, rather than killing them.
The absorbed cells send no signal to the body, and so are not replaced.
HIV syncytia marginate into the surrounding tissues, causing inflammation.
Inflammation draws other T-cells to the marginated syncytia, where they are absorbed by them.
This process repeats itself until enough cells have been absorbed to cause the immune system to collapse.
WHAT'S THE BIG DEAL?
The big deal is that The THEORY suggests certain diagnostic and therapeutic options that are contradictory to most of our current approaches to investigating and treating HIV.
It also predicts that the newly developed treatments will likely never eradicate the virus, since virtually none of them kill off infected cells. This would require HIV patients to continue treatment with high levels of expensive and toxic medications forever, placing a strain on both the body of the patient, and the price of healthcare. Like it or not, this IS the scenario that is currently playing itself out.
WE NEED TO FIND BETTER AND CHEAPER TREATMENT OPTIONS.
To that end, we need to keep an open mind and investigate all leads. Otherwise, we risk trapping ourselves in a scientific cul-de-sac that results in the development of expensive therapies that are only partially successful.
For those of you who have stuck around this far: the basic THEORY has been described in this section and THE NICKEL TOUR. Virtually all of what you really need to know has already been presented. It is my intention to present one more segment, called The FULL MONTY. It will deal primarily with the implications, consequences and additional questions that The THEORY raises in light of more detailed scientific investigation. (Things might get ugly.) It will touch upon such complex and hard-to-understand things as cytokines, inflammatory responses and Howard, The Aspirin Guy. (Sorry, Howard: I couldn't resist.)
So, if any of you feel you'd like to leave now.... well, you've been warned.
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 (deceased)