[quote name='samoth' timestamp='1310044954' post='4832257']
The magical anti-aging treatments mentioned in his article are science fiction at best, unrealistic otherwise.

The magical anti-aging treatments already have prototypes that are working on mice.[/quote]Look, breeding a knockout mouse that lives for 4-5 years is one thing. Gene theapy on a living human, especially as a routine maintenance thing at your local doctor, and within the next 20 years, is another thing, it's bullshit.

For gene therapy to happen at all, you would have to know the genome. We don't. Sure enough there is a lot of research, and every now and then someone finds a bread crumb. Sure, every major pharma company has a million genes patented, including some human ones. Blah, so what.

It's all good for nothing, because it neglects a fundamental property of life: Everything in nature/life/biochemy/biology serves more than a single purpose. Pharmacologists learned this lesson the hard way (or rather, did not learn it, but made the same mistake again and again). Interfering with one pathway always influences another two or three. This is true on all scales from entire ecosystems down to the molecular scale.

As a very easy and well-known example, take aspirin, a veneralble and well-known drug. It had been used for headache for over a hundred years before it was discovered that it affects platelet aggregation as a side effect. You can see this as a nice property, because it reduces the risk of a coronary incident, be that as it may. At the same time, it causes ulcers in the stomach and the duodenum, and in case you give it to a young baby, you'll have the nasty surprise of the Botalli duct not closing as it should. Why does this happen? Because the affected enzyme (cyclooxygenase) has at least half a dozen different functions at different times in different parts of the body. The very same thing is true for serotypes and genes. Several HLA genotypes are known to be affect half a dozen of different, and sometimes unrelated diseases each (positively or negatively). Another example would the an interleukin gene (I forgot which one). There exists a mutation which presumably renders the individuals (at least partly) resistant to HIV infection. Sounds like a good thing to do in gene therapy as standard procedure! Unluckily, the same variant causes a high incidence of Crohn's disease and MS.

The only way to safely rule out these prospective and yet unknown negative effects of modifying genes would be to do try each modification separately on a few thousand people (not knowing whether it may kill them or cause severe defects) and monitor them for at least 50 years. After this, one would have to try combinations of several modifications on another few thousand people and monitor them for some decades. All without being sure what damage you possibly do to them. And now tell me an ethical way of doing it. Oh, and did we say we want it within the next 20 years?

If you change the genome of a cell, chances that the surface markers change are high (more likely than not). If the surface markers of some subset of your cells change, you may quickly find yourself in a situation somewhere in between a more or less severe graft vs host reaction and instant death by anaphylactic shock. It all depends a bit on what marker changes, how tolerant your immune system is and on how lucky you are (this is actually a good thing, it is one of the natural mechanisms that protect us from cancer). It just isn't quite so cool if your immune system attacks your liver or your brain. Did Mr. de Grey suggest stimulating the immune system on top?

The only two solutions around this problem would be
a) combining the process with immunosuppression and radiotherapy, followed by bone marrow transplantation
b) making all modifications very acutely timed at the same time, in all cells
Good luck with solution a), my prayers are with you. And solution b) ... well... here's where sci-fi really starts.

For solution b) you would need either nanobots or a retrovirus. Except nanobots are ridiculous. Sure enough, it is possible to build machines at nanometer scale, but the smallest memory chip and the smallest processor that could possibly store enough information and have enough computional power to do a task remotely similar to "complex manipulations of nucleid acids inside a living cell, fully autonomously and failsafe" is a dozen orders of magnitude larger than "nano" and needs a power source that is also a dozen orders of magnitude larger than anything you could realistically inject into a human. Not even the most advanced robots built by the NASA (carefully assembled unique machines) can be considered 100% autonomous and failsafe. They do kind of ok roving over uneven terrain and picking up some rocks, but you surely would not want them to play with the DNA in your heart muscle, your white blood cells, or your central nervous system.

But of course there is still the retrovirus, oh joy. Retrovirii are great, except that they are very variant by their very nature and that many retrovirii are cancerogenous (in fact, at least in theory all of them can be). Admittedly, their stochastic self-assembling process is stunning, but this is definitively not something you want to rely on as a "failsafe" thing for modifying all cells in your body in a synchronized, timed manner.
Yes, there is research going on about injecting retrovirii that are conditioned to the particular surface markers of a tumor, but destroying the target tissue is a different story, and the therapy is only for the desperate, too.
Besides, not all tissues in the body have the same surface markers, so to change the genome in all tissues, you would need a vast number of different retrovirii. The immune system can somehow tell which cells belong to the body and which ones don't, regardless of certain different combinations. Alas, what can you say, the immune system is more intelligent than we are.

So, to summarize, we don't remotely know enough, and we don't remotely have the technical means, but Mr de Grey sees it happen as "routine maintenance" within the next 20 years.

For gene therapy to happen at all, you would have to know the genome. We don't. Sure enough there is a lot of research, and every now and then someone finds a bread crumb. Sure, every major pharma company has a million genes patented, including some human ones. Blah, so what.

they already do gene therapy on humans and they've already cured a patient of HIV using a combination of that and stem cell transplants.

It's all good for nothing, because it neglects a fundamental property of life: Everything in nature/life/biochemy/biology serves more than a single purpose. Pharmacologists learned this lesson the hard way (or rather, did not learn it, but made the same mistake again and again). Interfering with one pathway always influences another two or three. This is true on all scales from entire ecosystems down to the molecular scale.[/quote]
Why does it neglect that property?

[color="#1C2837"]The only way to safely rule out these prospective and yet unknown negative effects of modifying genes would be to do try each modification separately on a few thousand people (not knowing whether it may kill them or cause severe defects) and monitor them for at least 50 years. After this, one would have to try combinations of several modifications on another few thousand people and monitor them for some decades. All without being sure what damage you possibly do to them. And now tell me an ethical way of doing it. Oh, and did we say we want it within the next 20 years?[/quote]
[color="#1C2837"]why would you have to monitor them for at least 50 years? Success or failure of the procedures should be easily found within a year of the termination of the therapies. You don't need to wait until someone dies to tell if their body is growing younger rather than older, and any major side effects should be detectable even if not yet manifested shortly after (<5 years). Either way the claim was that they'd be able to in 25 years, not that it would be readily available in 25 years. I don't think that's an
[color="#1C2837"]enormous stretch. We already have the technology and scientific knowledge to implement most of his 7 treatments it's just a matter of doing the footwork on them.

[color="#1C2837"]

[color="#1C2837"]If you change the genome of a cell, chances that the surface markers change are high (more likely than not). If the surface markers of some subset of your cells change, you may quickly find yourself in a situation somewhere in between a more or less severe graft vs host reaction and instant death by anaphylactic shock. It all depends a bit on what marker changes, how tolerant your immune system is and on how lucky you are (this is actually a good thing, it is one of the natural mechanisms that protect us from cancer). It just isn't quite so cool if your immune system attacks your liver or your brain. Did Mr. de Grey suggest stimulating the immune system on top?[/quote]
[color="#1C2837"]you could also CURE IMMUNODEFICIENCY

[color="#1C2837"]The only two solutions around this problem would be[color="#1C2837"]a) combining the process with immunosuppression and radiotherapy, followed by bone marrow transplantation
b) making all modifications very acutely timed at the same time, in all cells
[color="#1C2837"]Good luck with solution a), my prayers are with you. And solution b) ... well... here's where sci-fi really starts.[/quote]
[color="#1c2837"]They already have a solution for the problem. It was found in May 2006.


[color="#1c2837"]

[color="#1C2837"]So, to summarize, we don't remotely know enough, and we don't remotely have the technical means, but Mr de Grey sees it happen as "routine maintenance" within the next 20 years.[color="#1C2837"][/quote]to summarize. I don't believe you are fully aware of what we have the technical means to do as far as gene therapy and stem cell research go. One troubling point that may affect it would be stem cell legislation, but I don't know if the SENS stuff can use bone marrow or blood stem cells instead of embryonic.


[color="#1c2837"]But feel free to focus on the negative possibilities of aging longer while ignoring the possibilities that would become available just having great minds useful lives extended by just 10 years let alone 900. I would love to see the argument that we would not have expanded our collective knowledge-base tremendously were minds like Tesla and Einstein still alive today.

There is a good analogy for the mouse longevity prototype which I forgot to mention. This is akin to ants which lift 20 times their body weight. Some people say this is comparable to us lifting a car with one hand. It is not. Similarly, when a beetle drops from 60 cm chair, some people say this is like us falling from a 12-story building. It is not. You cannot "upscale" things in such a naive manner.
For an animal that has a normal programmed lifespan of 2 years, the usual causes of human death simply don't exist. Thus, it may be possible to cheat on its "programmed death", but that does not scale to humans. I would be positively impressed if someone presented to me a 120 year old mouse, but until that happens it is meaningless.

The HeLa (Henrietta Lacks) cell line is immortal. What does it mean for extending your life, or mine? Nothing. It just means the cells are malfunctioning as they refuse to die as they should (which cynically was the cause of Mrs. Lacks death).

they've already cured a patient of HIV using a combination of that and stem cell transplants[/quote]
Good news for the approx. 30,000 people who still die from AIDS every year. Having said that, you probably refer to Hütter, Nowak, Mossner et al. NEJM Feb 12, 2009. This particular experiment, a patient suffering from both HIV and AML was given stem cells of a 100% HLA-compatible donor that was homocygote CCR5(32)-deficient.

Wow, that's a combination like winning the lotto jackpot. Cudos to Mr. Hütter for finding the impossible.
But otherwise, in the context of "living forever", it's not impressive or meaningful at all, and "cured HIV infection" is a misinterpretation.

CD4-deficient or CCR5-deficient cells will obviously not be infected with (the currently known phenotypes of) HIV, because these are the biochemical preconditions for the virus entering the cell. They have other problems of their own, though (this is a common thing in nature, many not-immediately-lethal defects give an evolutionary advantage in some niche, take sicklecell anemia as an example). It is a lucky combination that the patient suffered from AML, too. So effectively they replaced his entire collective of lymphocytes with a new, unconditioned one, and thanks to the very special conditions this did not kill the patient.
So, this is not curing a HIV infection, but no occurrence of HIV infection on cells which are not susceptible to HIV infection.
Which, admittedly, is still cool because it worked, but... still nothing special in respect of our topic. Unless you can pull the jackpot every time on demand, it means nothing for you and for me.

Why does it neglect that property?[/quote]
Because the assumption is "great, we know what this gene does, so it's ok to tamper with it, we are the best", and the truth is more like "we believe that we know one thing (of maybe 5 or 10 things) that this gene does". Tampering/botching with someone's health and life in such a drastic, dangerous, and final way, not knowing what will come out is unethical and also illegal in most countries. Josef Mengele was hunted for less and only escaped being tried and hung in Nürnberg because he believeably feigned his own death before making off to south america.

why would you have to monitor them for at least 50 years? Success or failure of the procedures should be easily found within a year of the termination of the therapies.[/quote]

1. Many heretidary diseases only manifest after 10-30, sometimes 50 years. Onkogenic effects (including in particular retrovirii) often manifests after several years, sometimes decades. Tampering with someone's DNA therefore means you must monitor them for at least that long.
2. Before applying a modification that enhances your lifespan, you must find it. Many treatments in medicine cure a symptom or even the disease, but do not make the patient live longer on the average. You can find many well-known examples for this in cardiology (which is a very well researched field). Therefore, any modification that you make, even if it seems to make sense and appears to have a positive effect, is not certain to really bring you closer to your goal.
   The only way of knowing whether modifying a gene will increase the lifespan is to try with a sufficiently large group (without knowing what happens!), wait until everybody has died, and compare the results to a placebo group. Or, you would have to build a huge genotype database, and sort specimen into two groups differing by one genotype. For this, you would need huge sample sizes (in the billions) to rule out other accidentially favourable/unfavourable genetic combinations and environmental effects. You would then have to track the deaths of all these and compare the groups. Good luck with the logistics, privacy laws, and acceptance in the population.

you could also CURE IMMUNODEFICIENCY[/quote]
Oh the joy. An article in USA Today which starts with the words "seems to", referring to a study without giving a concrete reference ("this thursday" on an unknown date).
The actual NEJM article that this refers to (January 29, 2009) is an overview containing lot of blah blah about how great gene therapy works without providing any hard data. There also exists an interview from Jan 28 in which some vague data is given.

The results of this study are that 8 of 10 patients were currently not under treatment and none of them had died within the follow-up time. Mind the wording, precisely.
Great news, except it is neither a particularly intersting story, nor trustworthy, nor relevant.

• The gene therapy is limited to a single tissue (white blood cells)
• The therapy was done "before the age of 2 in every case", i.e. none of the babies was older than a year
• Of course you would not expect the immunologic problems that I pointed out in my earlier post, since
  a) the immune system is heavily impaired (the very reason for the therapy) -- this is the same special precondition as in the HIV+AML case
  b) the immune system of newborns is still in a "shapeable" state
  c) memory cells and humoral defense as we have them are nonexistent yet
  d) leukozytes are conceptually the least troublesome special case

• The follow up is well within a timespan that the children would likely live without treatment anyway (2-8 years, mean 4 years)
• The follow up is not within a timespan to safely exclude leukemia or other negative effects
• Given such the particularly small study size (10 specimen) and the very select collective with an extreme compliance (parents of a mortally ill child), a consistent follow up is possible, likely, and expected. You probably have not worked with parents that have a terminally ill child before, or you would know. They will not miss follow-up as long as they are breathing.
• A factual follow-up ranging from 2 to 8 years strongly suggests that the data is "optimized" for a positive outcome (i.e. following up on the child that lives for 8 years, and not following up on the ones that die after slightly over 2 years).

The only interesting (stunning, frightening) thing about this study is that someone actually managed to convince an European (Italian) ehtics commision to allow such experiments on newborns.

There is a good analogy for the mouse longevity prototype which I forgot to mention. This is akin to ants which lift 20 times their body weight. Some people say this is comparable to us lifting a car with one hand. It is not. Similarly, when a beetle drops from 60 cm chair, some people say this is like us falling from a 12-story building. It is not. You cannot "upscale" things in such a naive manner.

That's not even relatively similar. Increasing the lifespan of another mammal significantly is totally relevant to increasing the lifespan of humans. Your metaphor doesn't even use the same branches of science for it's two cases; one is a physics problem and one is a biology problem.

I'm really dumbfounded how you are now arguing against the validity of using mice for drug trials.

Good news for the approx. 30,000 people who still die from AIDS every year. Having said that, you probably refer to Hütter, Nowak, Mossner et al. NEJM Feb 12, 2009. This particular experiment, a patient suffering from both HIV and AML was given stem cells of a 100% HLA-compatible donor that was homocygote CCR5(32)-deficient.

Wow, that's a combination like winning the lotto jackpot. Cudos to Mr. Hütter for finding the impossible.[/quote]
I would be ecstatic if I had HIV and even one person was cured of it. Maybe I'm just not satisfied with rolling over and dying.

And it's like winning the lottery of the lottery had a 1:10-20 chance of winning. 5-14% of europeans have CCR5-32. That aside, there is an enormous difference between someone being cured with difficulty and nobody ever being cured ever. I would take the former every time.

the book you wrote for one sentence questions
[/quote]

You're right; we should never strive to better the human condition ever as that might cause us to actually be capable of solving problems that currently exist and lord knows I'd rather be stuck in an overpolluted tirdhole where nothing interesting ever happens beside the occasional wardrobe malfunction of a ditzy heiress. STRIVE FOR MEDIOCRITY WOOOOOOOOOOO.

I'd love to see the resume of a 900+ year old living today.


...

1140 - 1160 AD : Leech Collector
Responsibilities:
- Collected leeches for medicinal purposes
- Blood letting
- Selling leeches to doctors


In all seriousness, I don't think dying is bad if the process of getting there does not involve suffering. I think medicine research should concentrate on eliminating the suffering aspect, not death.

If people could live to 1000, they would be incredible valuable after say 200 years of experience. I doubt he would be a leech collector at 700 years old.. More likely "Village elder co-leader of the Clan McCloud".. Probably less than 1% will ever live long enough to even reach 500 years old.. that is if people could live 1000 years.

-ddn

If people could live to 1000, they would be incredible valuable after say 200 years of experience. I doubt he would be a leech collector at 700 years old.. More likely "Village elder co-leader of the Clan McCloud".. Probably less than 1% will ever live long enough to even reach 500 years old.. that is if people could live 1000 years.

-ddn

I'd be interested to see how accidental death and murder would affect the average life expectancy when people live longer than 200 years.