Saturday, December 25, 2010

Life Lines 97 -- Saboteurs of the Cell

It is not easy to think very small. We like to think of small as something about the size of a dust mote, a speck barely visible to our eye. That’s big compared to almost any cell of our body. Thousands of cells can fit on the head of a pin. Without a microscope those cells would be invisible to our eyes. Yet a single cell is immense compared to a virus. Most viruses cannot be seen by microscopes that readily reveal bacteria. Viruses are organisms that are hundreds to millions of times smaller than any of our cells.

We know of viruses as germs, and we lump all organisms that cause disease under that term. Until the 1940s it wasn’t clear what viruses were. Some did not think they were organisms. Some thought they pre-exist in cells and are just jarred loose from their slumber inside the cell. A few could not distinguish between viruses and genes. Several things changed our views about viruses and much of that work was worked out more than 70 years ago on Long Island at Cold Spring Harbor. Max Delbruck, who left Nazi Germany to study genetics began using bacterial viruses in 1938 at Cal Tech. He got together with other scientists at Cold Spring Harbor and worked out some of the first experiments to show that bacterial viruses were more complicated than genes, that they had a life cycle, and that the bacteria on which they fed underwent mutations making them resistant to infection. A new instrument, installed at Cold Spring Harbor, the electron microscope, revealed the viruses as lollipop-shaped organisms that attached to bacterial walls by their stems.

Most bacterial viruses are big as viruses go. They contain 100 or more genes. Most of the genes that make us sick are much smaller such as those causing polio, flu, measles, or mumps. On average they contain about 10 to 15 genes. Human immunodeficiency virus, which causes AIDS, is also small but it is more complex in structure and function. Viruses can be crystallized because they are just molecules of nucleic acid and protein. They have no metabolism of their own and they subvert the cell by taking over its metabolism. They are like smuggled tapes inserted into a tape recorder.

We know the story of small David slaying the giant Goliath. A virus is much more tiny than the cell it infects. As the infected cell releases hundreds of new viruses, the viruses spread and in a day’s infection staggering quantities of virus can be produced. If they overwhelm the immune system, the virus infection can kill. This happens with such terrifying diseases as yellow fever or small pox. The 1919 variety of flu was another killer, turning young adults overnight from health to drowning corpses, the lung’s air sacs bursting and filling up with blood. Fortunately most viruses are not that lethal.

It is difficult to kill viruses once they are in the cell. Most of the things that damage the viral genes also damage human genes; most of the substances that damage the virus proteins also damage human proteins. This is why most virus diseases are prevented by vaccinations. It took many years to make safe vaccines against polio. It should not surprise us that the prevention of AIDS by vaccine may still be several years away.

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