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The feasibility and desirability of indefinite youth: recent advances from unexpected quarters Aubrey de Grey Department of Genetics, University of Cambridge Email: email@example.com Website: http://www.gen.cam.ac.uk. Structure of this talk Feasibility the “seven deadly things”
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The feasibility and desirability of indefinite youth: recent advances from unexpected quarters
Aubrey de Grey
Department of Genetics, University of Cambridge
What is your big idea?
Metabolism (the hugely messy network of homeostatic processes that keep us alive)
Pathology (the hugely messy network of antihomeostatic processes that kill us)
This is not controversial -- indeed, it is why most biogerontologists think there’s little hope of curing aging for ages
Aging is indisputably a side-effect of essential biochemical and cellular processes
Its functional effect (loss of performance) is delayed
Putting it another way:
Being alive must have immediate side-effects, since metabolically active molecules are short-lived
Those effects must accumulate, and have a threshold level below which they are harmless
Metabolism ongoingly causes damage
Damage only eventually causes pathology
This turns out to be very useful
Gerontology Engineering Geriatrics
Metabolism Damage Pathology
Claim: only the “engineering” approach can achieve substantial extension of human healthspan any time soon
That’s all a bit abstract and theoretical, innit?
Yes, but that’s just an analogy: why believe it?
The seven deadly things
How do you know this list is complete?
de Grey 2000, Trends in Biotechnology 18:394-399
Gearing 1986: one small protein relocated in yeast
Nagley 1988: shown to be functional
Galanis 1991: a second small protein relocated in yeast
Lander/Lodish 1990: suggestion of therapeutic potential
Zullo 2000 (after 9 years): one big protein in rodent cells
Manfredi 2001 (after 6 years): same one in human cells
Guy 2002 (after 1 year): a different one in human cells
1990: Chlamydomonas reinhardtii mito. genome sequenced
SIX of the “dirty baker’s dozen” missing!
Feb 1998: NONE cloned; AdG starts complaining about this
July 1998: King/Gonzalez-Halphen collaboration begins
~2001: C. reinhardtii COX2, COX3, ATP6, ND4L cloned
2002: C.r. ATP6 found to work unaltered in human cells
1991: Vigna radiata COX2 cloned
2002: importability found to depend on TWO a.a. changes
Derive 13 cell lines, each mutant for just one protein
Develop constructs that rescue respiration in these cells
Combine all 13, seek respiration without any mtDNA
Assay competence in mice using germline transformation
Assay competence in mice using somatic gene therapy
--- to get to here should take 6-8 years ---
6) Test in humans as for mitochondriopathies
- Lysosomal junk causes atherosclerosis, macular degeneration and most -- if not all -- forms of neurodegeneration
- It accumulates because we lack enzymes to break it down
- Such enzymes seem to exist in some soil bacteria!
- As with plant mitochondrial genes, these can in principle be exploited therapeutically
Convincing the world that aging is bad:
futile until we really rejuvenate mice?
breaking the global trance
Consider some standard excuses for condemning 100,000 people to death, every day, forever:
“Wouldn’t it be crushingly boring?”
“How would we pay the pensions?”
“What about starving African children?”
“Dictators would rule forever!”
Claim: nobody is really that dumb
-- they MUST be in a trance
Who's Afraid of Life Extension?
Harry R. Moody, Institute for Human Values in Aging International Longevity Center-USA
When I began to prepare to write this article, I was clear and confident about my direction. Anti-aging technologies, I was sure, are a snare and a delusion … It is a line of thought I have held for many years …
But the more I thought about my skepticism and hostility to life-extension technology, the more uneasy I became. Gradually, as I reflected on my uneasiness, I found it more and more difficult to rationalize my strong rejection of life extension.
… within mainstream gerontology, anti-aging medicine is widely viewed with hostility and skepticism (an incipient form of “gerontological correctness”?). But we are entitled to wonder: Are the arguments against anti-aging medicine valid, or are the opponents of anti-aging medicine (including me) simply gerontological Luddites?
If one lifelong opponent can wake HIMSELF up, there is hope yet…
“Offensive.” “Grotesque.” “Revolting.” “Repugnant.” “Repulsive." These are the words most commonly heard regarding the prospect of human cloning. .... Even Dolly's creator has said he "would find it offensive" to clone a human being.
Revulsion is not an argument; and some of yesterday's repugnances are today calmly accepted -- though, one must add, not always for the better. In crucial cases, however, repugnance is the emotional expression of deep wisdom, beyond reason's power fully to articulate.
Would anybody's failure to give full rational justification for his or her revulsion at these practices make that revulsion ethically suspect? Not at all. On the contrary, we are suspicious of those who think that they can rationalize away our horror
Leon Kass, 1997, “The Wisdom of Repugnance”
Leon Kass said it
Our wisdom about aging is precisely a wisdom of repugnance -- well, mine is…
Repugnance can go down as well as up
- Business:promoting “anti-aging” products
- Policy:“open-mindedness” -- anyone can buy a stall at the expo right next to the meeting, sell magnetic water or whatever, and they do
- Interpretation:profit first, efficacy second
- Resulting reputation:oiliest of the snakes
“Anti-aging medicine does not currently exist, in the sense in which the term ‘medicine’ is generally used. Medicine is biomedical technology that, at least for most recipients, effectively treats the primary symptoms of the condition against which it is claimed to act. The primary symptom of aging is indisputably death, and no existing product appreciably delays death from aging.”
And what happened?
The anti-A4M movement (Olshansky, Hayflick) is backfiring, because everyone who sells anything downplays its flaws - hence their criticism is not considered fair
The “A4M community” are in much less of a pro-aging trance than most people
They are numerous and their customers quite affluent
They want their business to last long-term
Points to be carefully noted:
1) Fundamentalists (very numerous, very powerful) do, in the end, follow the doctrine as it evolves
2) God deprecates hastening death, however good the afterlife is claimed to be
3) God also deprecates apathy
The most invulnerable to the life-extension crusade is “Yes, we should cure aging ASAP, but I don’t feel like it”
Little known fact: Len Hayflick looks after his health
Phenomena not to be ignored:
- Death penalty abolished throughout Europe
- Vietnam war rather less popular than WWII
- Britain banned gun ownership after one mass murder
- No war in Western Europe for 59 years - not seen since Roman times
- Canada (and Norway, etc)