Posted by Thermus aquaticus on Feb 17, 2002 at 19:42
(129.59.237.200)
Re: Dolly, the Sheep, Put Down due to Disease (Mike Kremer)
*Prehaps all living cells "are aware of their age"?
So that if you clone from six year old sheep cells
The resultant cloned sheep is six years old from birth?
Now why are Cancer cells virtually immortal?
(Tough question for- Thermus aquaticus)
Tough? Nah! :)
Dolly was cloned from the mammary cell of a 2 year old sheep. It was shown that telomere length was not restored by the process of nuclear transfer. (It was an open question whether or not the adult somatic donor nucleus would initiate telomerase expression when “reprogrammed” to the zygote stage. Apparently not.) So, at the cellular level, Dolly’s cells were already 2 years old from the start of embryonic development. Thus, her cellular age was 2 years older than her developmental age. But, as mentioned in my post below, telomere length does not normally reduce to the point where genomic instability occurs within the course of a single mammalian lifetime. So this 2 year discrepancy and slightly reduced telomere length is very unlikely to have caused Dolly any harm.
It will be interesting to hear the post-mortem result. Dolly’s arthritis was never direct evidence of a cloning-related abnormality, although it was suspicious. Now her death due to a lung disease, although again not direct evidence of a cloning-related abnormality, is very suspicious. Not that it is a great surprise. Virtually no cloned vertebrates of any type escape developmental abnormalities (many of them severe) as a result of cloning by nuclear transfer. This is why the cloning of humans should be illegal.
Good-bye Dolly.
(Dolly and her lamb Bonny)
*Prehaps all living cells "are aware of their age"?
Nearly all eukaryotic cells are aware of their age. Prokaryotic cells (ie. bacteria), on the other hand, are immortal. In a sense, the bacteria that are alive today are the same bacteria that were here 4 billion years ago. They never died, merely divided by binary fission to produce clones of themselves and evolved as they went. One of the major traits that distinguish prokaryotic from eukaryotic cells is senescence (ie. programmed cell death). Unlike bacteria, vertebrate cells are programmed to die (the only exception being the various tissue specific stem cells). In order to achieve this, cells need to know how old they are. They keep a careful track of their age via a number of different mechanisms, none of which I am particularly familiar with. One of the mechanisms, as already mentioned, is telomere length. Cells will only divide a certain number of times before they commit suicide. This number is known as the Hayflick Limit, which various from organism to organism.
Now why are Cancer cells virtually immortal?
This is a way complex a question! They have escaped the programmed senescence, and can keep on dividing way past their Hayflick Limit. For a cell to become cancerous, it has to acquire a whole range of different mutations. Cells don’t become cancerous overnight; it takes a long time, a great deal of luck (or bad luck as the case may be) for a cell to acquire all the necessary mutations. This is why cancer is predominantly a disease of the elderly. The hallmark of a cancer cell is its uncontrolled proliferation. Normally, a cell has a very tight control on its division so that it divides only at the right time and place. A large number of genes play critical roles in controlling cell division. When cell division goes wrong, there are a number of mechanisms that make the cell commit suicide rather than risk passing on defective genes. Thus, a cell needs to acquire a variety of mutations to overcome all these control mechanisms so that it can be immortal and divide uncontrollably. Then the cell needs to acquire telomerase activity to restore its telomere lengths. Then it needs to acquire the ability to “de-differentiate”. Then it needs to acquire the ability to stimulate blood vessel growth to feed the new growing tumor. Then it needs to acquire the ability to avoid the immune system that is trying to kill it. Then, for metastatic cancers, it needs to acquire the ability to delaminate from its site of origin, enter the bloodstream, travel to a new site in the body and migrate out of the bloodstream into the new tissue.
It’s a lot of “ifs” and “maybes”, but there are a lot of people and a lot of cells in the world, so this series of mutational coincidences happens quite a lot. And when it happens, these “super cells” are often very hard to remove from the body.
(I have generalized greatly in this post, but hopefully you get the idea.)