Map of life expectancy at birth from Global Education Project.

Sunday, February 13, 2005

Weird science?

A big issue nowadays with the foundations and clinical care institutes is Health Literacy. The short version of what this means is, "Do people know what the heck their doctors are talking about?"

No, they don't, and that includes people who have lots of education and are good at finance, gardening, cooking, child rearing, chess, music, architecture, 16th Century Chinese literature, and automobile mechanics. What most of us don't know squat about, for some reason, is biology. What we ourselves are. I'd like to lay out a few basic facts which are highly relevant to commonplace medical problems, and then go on to the specific example of HIV which happens to be how this discussion started. Then I'd like to invite readers to let us know if they learned anything, or if it was all completely familiar to them.

First of all, we are made of eukaryotic cells. Those are cells with a nucleus, and they have other important features such as mitochondria, and ribosomes. All multicellular organisms -- animals and plants -- are eukaryotes, but bacteria are not. All cells, including bacteria, are enclosed in a waterproof membrane. In eukaryotes, the cell's DNA is located in the nucleus.

DNA is an extremely long molecule that is analagous to a strip of old-fashioned magnetic tape once used to store computer programs. DNA is a long chain of codes corresponding to various molecules called amino acids, which when strung together in their own long chains form molecules called proteins. Proteins have an astonishing variety of properties. Some of them serve as structural elements of the body, others control various chemical reactions, others have essential roles in protecting the body against intruders, etc. Shorter strings of amino acids may serve as signalling molecules between cells and organs of the body. The activity of these various proteins and signalling molecules controls our development from fertilized egg to adult, and our biochemical functioning, including our feelings and thoughts.

Sections of DNA, called genes, contain the code strings defining various proteins and signalling molecules. Some proteins actually control the reading of genes to produce new protein molecules. Others repair damaged DNA. A molecule called messenger RNA is "transcribed" from DNA and then carries the instructions from the nucleus out into the cells ribosomes, where other molecules called tranfer RNA go out and get the required amino acid from the intracellular fluid and assemble them into the correct chains. Complex interactions and feedback loops among the external environment, the internal environment of the cell, and the various proteins and signalling molecules, determine which pieces of DNA will be read and when. All our cells have the same DNA, but different types of cells have different segments of DNA permanently turned off.

Viruses are not really alive. They cannot eat, or grow, or move. They just float around in our bloodstreams. They consist of some genetic material in a little protein package. Most of them consist of DNA, but HIV is actually RNA.

Cell membranes keep the good stuff inside the cell, and keep bad stuff out, but they have to be able to take in what they need and secrete what they're supposed to, so they have protein structures called receptors embedded in their membranes that act like gateways, letting in what needs to come in. When HIV happens to bump into a receptor called CD4, on a certain kind of white blood cell called a T-lymphocyte, its protein coat has the key, and HIV's RNA gets into the cell. Their, part of its RNA synthesizes an enzyme called Reverse Transcriptase, which runs the genetic system in reverse and makes DNA based on code contained in HIV's RNA. When this DNA is read, in turn, it makes the rest of the protein and RNA components of HIV. Some of HIV's proteins actually consists of different pieces cut out of the same chain of amino acids, so another HIV protein, called a protease enzyme, cuts the chains into the correct pieces. Then all the pieces assemble into new virus particles. When there are enough of them, the cell disgorges them. Eventually, its machinery hijacked to make HIV, the cell dies. It is the destruction of these cells that causes the characteristic immunodeficiency of HIV disease.

Whoo. Still with me? Here's where evolution comes in. The process of making DNA from HIV's RNA, and vice versa, doesn't always go perfectly. Sometimes one or more of those amino acids in the various chains is replaced by a different one. Sometimes this doesn't matter much, sometimes it makes the new HIV non-infectious, or less infectious. In the latter case, the progeny of that altered version will die out.

Now suppose we are taking a drug to control HIV. Most of them work by either stopping the action of reverse transcriptase, or stopping the action of protease. Now suppose we take the drugs all the time, on time, so there is always a good level of them in our bloodstream. HIV will scarcely be able to replicate at all, and our disease will be controlled. (Unfortunately, it will not be eradicated -- it will be there lurking in the DNA of some of our cells.)

Suppose we forget a dose one day. The virus will start to replicate. Then we take the next dose. If we're unlucky, somewhere among the millions of virus particles that got made while we were goofing off will be one that happens to have a mutation that makes its reverse transcriptase or protease work even in the presence of the drug. That one virus particle will keep replicating even though we are now taking our medicine again, and in a very short time, it will have billions and then trillions of descendants. We will now be infected with a drug resistant strain of HIV.

That process is called mutation and natural selection, i.e. evolution. It's how we got to be here in the first place to figure all this out.

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