Tuesday, 4 February 2014

Monkey Business: what does it all mean?

I am sure many of you read or heard about the new technological breakthrough that enables scientists to create apes with specific genetic modifications. As the Guardian put it:

         Genetically modified monkeys created with cut-and-paste DNA

So what is "cut and paste DNA" and how does this differ from the experiments to clone Dolly the sheep? The phenomenon that has been harnessed for modifying monkeys is called CRISPR which stands for Clustered Regularly Interspaced Short Palindromic Repeats. So what does this mean? It is a genetically programmed system found in most bacteria that allows specific DNA sequences (genes) to be inserted at a specific location in a chromosome, this means that a gene for a particular disease can be engineered into an organism that is very similar to humans. This allows us to test drugs in a better controlled setting. There will be those who consider this a dangerous step and those who see it as a major breakthrough. We looked at the history of model organisms in an earlier blog, so how does this development compare? What are your own views?
The problem with the use of model organisms or cultured human cells in the evaluation of new drugs lies in the differences between species and not the similarities. While there may be some drugs that target functions that are common to mice and men, there are some diseases that are organism specific. This is particularly true for pathologies associated with the nervous system and in particular the brain. Clearly, any unnecessary use of animals is to be avoided, but if we are to rely on data from animal experiments, we must be sure that we do not repeat the mistakes of the past: recall that thalidomide was successfully tested on rats and rabbits and given the all-clear. Any advances in developing a deeper and robust understanding of human pharmacology is to be welcomed.

How did Dolly the sheep get cloned. In Dolly's case, the nucleus of a set of breast cells grown in culture was carefully removed and the egg cell, reprogrammed with nuclear DNA. Shortly after, it was clear that this approach worked, but did epigenetics cause the cells to lose their DNA: Maybe we may never know? Dolly grew past pregnancy, but ended up with major chromosomal defects, caused in part by a loss of epigenetic signals and abnormal activities of the chromosome maintenance enzyme: telomerase, which prematurely aged Dolly. 

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