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Dr Who: The Lazarus Experiment - John C. Kirk — LiveJournal

May. 8th, 2007

01:00 am - Dr Who: The Lazarus Experiment

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From:karne_k
Date:May 8th, 2007 10:28 am (UTC)
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>In a similar way, the copies of our DNA in our cells gradually get degraded,
>and this accounts for things like grey hair and wrinkles.

No offence, but this is very, very, wrong :)

DNA replication is incredibly accurate with errors in the region of 1 in 10^4 to 10^5 base pairs, with the huge majority of these being caught and corrected by a variety of 'proofreading' systems. The final resulting error rate is about 1 base pair (in 3 billion for a human) per cell division. Since a large amount of human DNA is either not apparently in use or inactive, most of these errors have no effect or if they do, they kill the cell concerned. A very, very, small number activate oncagenes and result in cancers.

The primary 'damage' that happens to DNA on replication is telomere shortening. Due to the way DNA replication works (at least in eukaryotes), chunks off the end of the strands are lost or missed out at each copying cycle. The telomeres are sequences of non-coding DNA that act as buffers against this. Once the telomeres 'run out', the next replication cycle starts cutting chunks out of the encoding DNA - which in turn results in a poorly functional or (more likely) dead cell.

It seems likely that loss of telomeres from cells (and hence loss of the cells themselves) as tissue age result in some but not all of the effects of aging. It has also been suggested that telomerase – a telomere repairing enzyme found in eukaryotic germs cells – might be used to reverse some of these effects (assuming you can magically turn it on in all cells). The problem is that telomeres appear to explicitly evolved to limit the number of replication cycles a particular line of cells can go through (before it damages its own genome and dies) with the aim of reducing the effects of DNA replication errors and the resulting oncagenesis (cancer formation).

Hence, the aging process may actually be a symptom of the body being evolved to 'run as long as possible' before oncagenesis. The cellular damage that results is actually self inflicted and solving it (say via stem cell or gene therapy) doesn't actually help much until you can cure cancer.

PS: I'm a chemist not a biologist and the above is simplified for easy of explanation. Anyone reading this who knows more than me and spots errors – please forgive and explain them :)
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From:susannahf
Date:May 8th, 2007 11:00 am (UTC)
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If you believe in the premise of "The Selfish Gene" - which is reasonable but has some flaws, there is also an evolutionary reason for aging.

Assumptions:
1) Organisms exist to perpetuate their genetic information
2) Genes that confer advantage to offspring will dominate

From this you get the conclusion that the most "successful" genes will cause their carrier organisms to be highly fertile and resistant to disease. However, there are limited resources, so you can't be too fertile (otherwise all your offspring will die of starvation), and you shouldn't have infertile organisms (old people) using up resources that could be better spent on fertile or pre-fertile organisms.

So aging can be argued to be a desirable trait from an evolutionary point of view. Once you are no longer capable of passing on your genetic material, you die.

Of course, this is a gross simplification leaving out all sorts of aspects like post-fertile adults providing childcare and education while the fertile adults do the hunting and so on, but the gist still holds.
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From:karne_k
Date:May 8th, 2007 01:19 pm (UTC)
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I'm trying not to side-track the discussion too much, so I'll keep this short :)

>From this you get the conclusion that the most "successful" genes will cause
>their carrier organisms to be highly fertile and resistant to disease.

Not quite. The Selfish Gene says:

1 - genes exists to replicate (and replicate to exists)
2 - genes replicate via the mechanism of animals (plants, bacteria, slime moulds etc.)
3 - the most common genes are those that best help their animal pass on more copies of themselves

The latter means that the 'best' genes are those that best help their animal (i) survive within their ecological niche (or take over another one) and (ii) produce the most offspring *which in turn must survive to breed*.

This implies that diseases that occur after reproduction are irrelevant to evolution (although not the case with primate or other animals with significant levels of 'grandmother' infant care) and that high fertility is only required in situations of high infant mortality. Small numbers of well cared for offspring, whom in turn have an excellent chance of passing on their genes to their own offspring, are actually more valuable from the selfish genes' 'point of view' than large numbers of poorly/not cared for ones, many of whom die. Logically, the former strategy is aided by longer life spans and higher levels of intelligence. Cooperation between related individuals, group living, communication and the development of language also all help. Think pride of lions, troop of baboons or humans societies.

> However, there are limited resources, so you can't be too fertile

Efficient use of limited external resources isn't really an evolutionary issue per se, its effect is minimal unless an animals' breeding is so extreme that they use up all the resources in their niche before their offspring themselves can breed. The selfish gene isn't able to see the long term picture (please ignore my anthropomorphic terminology!), otherwise we'd not see the common cycle of 'boom-bust' in animal populations.

Dragging myself back to the point. I'm sure aging does have an evolutionary aspect, but I suspect that it's more a case of (i) how much internal energy/resources should be put into this individual breeding now vs living longer? and not (ii) when should this individual die off to allow their offspring access to its external resources?

As always, there are some special cases – spider mothers using their own bodies to feed their young, being one I can think of. In general though, the most powerful evolutionary forces are the simple ones – the ones that work directly on individuals and directly effect their breeding success.
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From:johnckirk
Date:May 8th, 2007 02:58 pm (UTC)
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I remember a line from a Spider-Man comic, where the High Evolutionary said that "cloning stagnates the evolutionary process". So, from the point of view of improving the species through natural selection, I'd agree that you don't want immortality for everyone. (I think it was one of the Dawkins books which said that evolution relies on non-random death.)

Thinking about genetic algorithms, the idea is that you start out with a pool of possible solutions, and then use them to generate new ones. However, unlike biological organisms, the old solutions don't automatically die out - they get compared to the offspring, and then the best subset from both generations combined gets to live on. So, there's no real concept of age: you may wind up with an original solution still intact after 70 generations, and it's just assessed on its own merits.
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From:karne_k
Date:May 8th, 2007 03:57 pm (UTC)
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[posted again, sorry John please nuke the anon post - I hate LJ sometimes! :) ]

Evolution is neither good for the species (which is an arbitrary descriptive label used by humans because we can understand it better than 'semi-closed subset of the available gene space') nor any individual in it. It fact it's not good for anyone; it's a natural process that occurs whenever you take information and process it in a 'genetic' fashion. You can see evolution occurring in e.g. software viruses and antivirus systems. The concept of the rightness of the 'March of Evolution' is a religious idea as much as any other. Humans have used evolution as a tool for millennia, whether it be for animal husbandry or microchip design - seeing it as anything else is silly :)

>However, unlike biological organisms, the old solutions don't >automatically die out

Don't relate a genetic algorithm's solution to an individual. A better relationship is between each separate test that you run on that solution (to check its efficacy) and an individual. You'll probably run hundreds if not thousands of tests (in order to get statistical strictness) and the same applies in nature. Old gene solution certainly don't die out - not at the time scale you're thinking of and mixing between the old and the new is very common. Indeed, the concept of generations of solutions in genetic algorithms is artificial (and imposed simply to make things easier for us humans); evolution in nature is a lot less quantised than that.

As in your example, if you take a culled population of say 1000 rabbits of a particular genotype and you put them through 70 generations (oo.. say a 50 years) in environment that they've evolved to match and if that environment doesn't change, then I'd fully expect the rabbits at the end to be very similar to the ones you started with. Unless they’ve evolved to avoid your culling technique, of course.

You'll also have one hell of a rabbit skin carpet...

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From:johnckirk
Date:May 8th, 2007 02:39 pm (UTC)
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Ah, thanks for the clarification :)

So, if you could use this telomerase stuff, you should still have enough good copies of your DNA (in an old person's body), without needing a sample from your younger self?
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From:karne_k
Date:May 8th, 2007 03:32 pm (UTC)
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Telomerase can be used to repair telomers, since the 'buffer' DNA that makes them up is meaningless, almost any non-cancer cell in the body would be sufficient recover a 'clean' DNA sample. Or you could get it from stem cells from bone marrow or the gonads or something and not bother with the telomerase.

The Dr Who science in this episode was utter junk btw :)
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From:shuripentu
Date:May 8th, 2007 10:05 pm (UTC)
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I haven't watched this episode, but if it was anything like the first episode, you have to hang your lab coat at the door to enjoy it. :)

Moral of the story: Just as the "first aid" on TV is a load of hogwash, so is the "science" on TV. And in books. And indeed on the news most of the time.

Which reminds me, I promised someone I'd explain to them why the "science" in Angels and Demons is a great big steaming pile of ocelot poo...
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