Sunday, November 14, 2010



Back in the 1950s I saw a movie called The Fly. Vincent Price played a scientist experimenting with teleportation (pre Star Wars no less) but as he moves himself a fly accompanies him and he emerges in two scrambled chimeras, his body with a fly head and forearm and the bulk of the fly’s body with his human head. It was a great science fiction classic and scared the wits out of those seeing it. Vincent Price was a master at horror pictures. Recently I read an item from a Belgian team at Antwerp and Louvain Universities. They isolated the normal and three different mutant forms of a gene associated with a neurological and muscular wasting disease. It is called the Charcot-Marie-Tooth syndrome [CMT]. There are mutant forms located on chromosomes 1, 16, and 17 as well as on the human X. Most are dominant mutations. Children with CMT begin to show muscle wasting in their lower limbs when they are approaching age 13. It is progressive and can cause lots of problems, including loss of sensation and progressive paralysis. In most the fatty sheath along nerve cells degenerates so nerve impulses cannot be transmitted. Some die early but others live into their 80s with the disease. There is no cure or treatment.

The Belgian group identified one of the genes involved for CMT as a near universal gene found in all cells from bacteria to humans. It is a gene associated with protein synthesis called YARS. The normal human YARS has no effect when inserted into fruit fly sperm or eggs. But any of the three mutant forms inserted had dramatic effects in the flies inheriting that defective YARS gene. They could not fly, they had difficulty moving about, and their nerves showed signs of the same deterioration of the fatty sheaths around the nerves. One could argue that the fruit flies were expressing CMT disease.

This is valuable because animal models are usually done with mammals, which are expensive to maintain and slow breeding. Fruit flies, by contrast, can be grown by the thousands in a matter of a couple of weeks. This will allow the Belgian scientists to study ways in which the YARS gene interferes with nerve sheath formation and maintenance. It may someday lead to drugs that might prevent that deterioration.

What strikes me as interesting is our perception of flies and science seen in 1958 and seen slightly more than a half century later. In 1958 it was pure speculation about what we share in common with flies. Very little was known about the biochemical functions or developmental functions of the genes in fruit flies. Today virtually every gene in fruit flies has been assigned a biochemical function and the sequence of every gene in fruit flies is known. A half-century of progress in molecular biology is making it possible to study human diseases in fruit flies. I do not doubt that counterpart genes in fruit flies will be found for Huntington disease and Alzheimer syndrome and that will add to our knowledge of how genes associated with the nervous system function when they are introduced into fruit flies and used to study the disease process at a molecular level. It may not be as exciting as a B rated horror picture, but to the families involved it will be a cause for hope.

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