In the 1990's, as scientists were conducting the human genome project, there was a belief that knowing the genome would explain all the mysteries of the body. Once we could decode our genome, we could customize medicine for our unique makeup.
This turned out to be a little optimistic.
Genes contain the codes for proteins, and that's all they do. Just knowing the code for a protein doesn't tell you much about that protein, though. Sometimes we are lucky, and we find that a disease is linked to a protein whose function we already knew. Most of the time it doesn't work like that.
Most of the time, a geneticist will study a group of people who have the same traits and look for common elements in their genes. The story of alpha synuclein, the protein that many scientists now believe is closely tied to the pathogenesis (i.e., cause) of Parkinson's, offers a nice illustration of how this happens.
As I wrote earlier, alpha synuclein was discovered in 1994. In 1995, researchers figured out what gene coded for alpha synclein and then, in 1996, a collaboration of NIH researchers with colleagues from the Robert Wood Johnson medical school and Seconda Universita degli Studi di Napoli showed that, in a large Italian family, they could link the family members who developed Parkinson's with a specific genetic location. Soon after, again under the lead of Mihael Polymerapoulos at NIH, the team showed that this was the gene that coded for alpha synuclein.
Even when it was discovered, Polymerapoulos and his colleagues knew that the mutation they had discovered could not explain very much of the Parkinson's disease that neurologists were treating in their clinics - few people would have that specific mutation. However, it didn't have to. Knowing that the gene for alpha synuclein was important meant that it was likely that the protein alpha synuclein was important - but how? In short order the next breakthrough came from the lab of Cambridge's Michel Goedert and his team: Lewy bodies, known to be present in the brains of people with Parkinson's since 1912, were composed of alpha synuclein.
Since then, further research has shed more light on the puzzle. A group of leading neurologists figured out that Parkinson's seemed to be transmitted into transplanted cells. This fueled the development of the prion hypothesis, that Parkinson's disease might be a prion disease. Northwestern's Dimitri Krainc, when he was at Harvard, tracing the clues from another gene associated with Parkinson's, explained a part of this mechanism. Others have provided more important clues.
The importance of alpha synuclein to current research is well documented. What's important about this story is that the genetic research didn't explain a genetic cause for the 15% of the disease that seems to be hereditary. Instead, a mystery that started with one Italian family with a rare genetic defect started us on the path to understand all of Parkinson's disease.
The idea that knowing your genes will explain your health hasn't panned out. Finding a genetic defect that causes Parkinson's isn't important just so that we can make genetic tests. Understanding genetic defects that are linked to disease can identify mechanisms that are important in those diseases. We originally thought that genetic tests would tell us how to personalize medicine for you. Instead we are finding that by understanding what genes are linked to aspects of each individuals health, we can identify ways to help everyone.
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