Wednesday, August 26, 2009

Latest breakthrough cannot eliminate all forms of cancer and diabetes

Cell mitochondria - highly enlarged - with their own DNA - able in some cases to transmit disease

Hereditary diseases, including cancer and diabetes, could be eradicated before birth, scream the headlines.
It hinges on new techniques for fixing faulty DNA.But not just any old DNA.

How can cancer and diabetes be prevented, given that those diseases, while having a genetic component, are not simple inborn errors of metabolism, but multifactorial - influenced by environment as well as genetics?

One has to read quite deep into the article to see the reasons for the apparent contradiction.

It's to do with mitochondria - those sausage-shaped subcellular organelles of which the typical human cell has a thousand or two (see graphic). Mitochondria play a key role in supplying the cell with energy, by providing a package of enzymes and electron-carriers that convert the energy of foodstuffs to ATP - the universal energy currency of living cells-  using molecular oxygen to release energy.

Remarkably, mitochondria have their own DNA. It's only a tiny proportion of the cell's total DNA, but certain diseases are due to defective mitochondrial DNA, as distinct from the predominant DNA in the cell's nucleus. The new technique prevents faulty mitochondria, with  defective DNA, passing on their defect to a fertilized human embryo, basically by transplanting the nucleus with its "good" DNA, leaving the bad mitochondrial DNA behind, and substituting "good" mitochondrial DNA.

So the technique only works for those variants of cancer and diabetes that are due to defective mitochondrial DNA.  Headlines that suggest that all cancer, or all diabetes, can be eliminated, are clearly misleading.

How come mitochondria have their own DNA? There is now an impressive amount of evidence that mitochondria are ancient bacteria that were somehow engulfed in early cells, and not only managed to survive, but set up a productive partnership. The host cell protected the bacteria, and the latter returned the favour by providing a highly efficient means of oxidising foodstuffs. Prior to the so-called endosymbiotic partnership, the host cells had to rely on glycolysis - the biochemistry of anaerobic fermentation in, for example, brewing and yogurt production, or anaerobic muscle metabolism, which provides a little energy without oxygen, which is not only far less efficient than aerobic metabolism, but generates potentially toxic endproducts (alcohol, lactic acid etc). The end-product of aerobic metabolism is gaseous CO2 - non-toxic because it is easily got rid of.

One curious feature of mitochondria is that is only the mother's mitochondrial DNA that is passed on to offspring.  Male gametes (spermatozoa) have mitochondria, but they are selectively destroyed in the ovum at fertilization. Mitochondrial DNA has proved of great utility in tracing human lineage back to one original  female ("Eve") in Africa, by avoiding the complication of all that invasive male DNA!

Further reading:  New Scientist article

  The Times  

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