Chasing the immortal strand: evidence for nature's way of protecting the breast genome

It is often noted that fashion goes in cycles; keep those old clothes in the wardrobe long enough and they will enjoy a renaissance eventually! It seems that this is also true of many great ideas in science. In a previous issue, Bussard and colleagues [1] reacquaint us with John Cairns' immortal strand hypothesis, postulated some 35 years ago [2]. Cairns' hypothesis still remains relatively unknown to the majority of cancer researchers, perhaps in part due to the more esoteric nature of his proposal, and the difficulty of proving it.Cairns published his hypothesis around the time that Knudson was popularizing Nordling's [3] concepts of multiple mutations being required for the genesis of cancer, through his own careful analysis of inherited retinoblastoma [4]. The notion of natural selection of cells carrying mutations that give a favourable survival advantage is now well established in cancer biology. However, Cairns recognized a problem with this concept: given the very large number of cell divisions in tissues like the skin, gut and bone marrow, he thought it surprising that there should be as little cancer as there is, if mutations arise at the rate that was estimated to be the case. Why was this so?Cairns focused his attention on the concept of adult stem cells that were understood to be responsible for the replenishment of rapidly dividing tissues, and to reside within cellular hierarchies in various tissues, such as the haematopoietic system. It was hypothesized that stem cells undergo asymmetric division, giving rise to two progeny: one destined to remain as an undifferentiated stem cell (self renewal) and one that could go on and divide again to give rise to progeny that expand in number and undergo differentiation. Various mechanisms whereby asymmetric division may occur have been elaborated in a recent review by Knoblich [5].The concept of a cancer stem cell is also enjoying a resurgence, having essentially been proposed by Julius Cohnheim in 1867 [6] whe