An engineering approach to defeating aging: issues of mindset and of mobilisation

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An engineering approach to defeating aging
issues of mindset and of mobilisation Aubrey de
Grey Department of Genetics, University of
Cambridge
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Biogerontologists
Peer review, short-termism
Media
Ballot box
Voters, shareholders
Government, industry
How can this logjam be broken???
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Solution 1 by a concerted attack on many
mutually-reinforcing but comfortable
fallacies Theres no evidence that aging can be
appreciably altered Theres so much in biology
that we dont remotely understand Aging is
good, it gives life its meaning Its more
important to compress morbidity The population
crisis would be unmanageable Replacing brain
cells would endanger continuance of identity We
must say nothing to cause optimism until we
succeed in mice Tyrants will reign forever
treatments will only be for the rich Science
only moves on when the old guard retire Well
be seen as charlatans failure will rebound as
loss of funding
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• Theres no evidence that aging can be
  appreciably altered
• Evidence from lucky guesses/potions indeed not.
• But did the Wright brothers have evidence that
  their plane would fly? Not from balloons or
  birds, since it neither floated nor flapped...
• This is a simple error -- applying the rules of
  science to something other than a scientific
  hypothesis (in this case, the feasibility of a
  technological venture). Why is it so pervasive?
  My take mindset. Only highly curiosity-driven
  (as opposed to goal-directed) people choose a
  career in basic science.

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Theres so much in biology that we dont
remotely understand Wrong answer Maybe, but
not for long Right answer Yes, and this will
long remain so, BUT how complete need our
understanding be? How fully must one understand
how a horse works, to get it to carry one in the
direction one wants? Not very fully at all.
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Evolution is smarter than you are
(Crick) Wrong answer 1 Maybe, but not for
long Wrong answer 2 Yes, but we can copy it.
Flaw humans are evolutions best non-agers, or
nearly (depending on the metric) Right answer
Yes, but it has (a) different tools, and (b)
different objectives. Examples (details in
tomorrows talk) To engineer mitochondria to be
better at importing very hydrophobic proteins we
are studying algae to engineer lysosomes to be
better at degrading recalcitrant aggregates we
are studying soil bacteria. Neither of these
organisms is known for its longevity.
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• Aging is good, it gives life its meaning
• To each his own....
• 2) Show me the data
• 3) This is an article of faith, we must live
  with it

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• Its more important to compress morbidity
• No it isnt. Poll after poll -- and also
  peoples actual behaviour -- shows that,
  ultimately, life is more valued even than health.
• Even if it were, this is of no interest, because
  compressing morbidity in affluent societies seems
  (from both demography and biology) to be
  impossible.
• What is possible, however, is to compress
  frailspan as a proportion of healthspan by
  increasing healthspan. Only in that way will we
  avoid the global nursing home scenario of
  Fukuyama -- without this, the falling birth rate
  will soon begin to increase the proportion of
  people who are in age-related frailty.

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What Congress was and wasnt told
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Healthy people dont die tomorrow
Cumulative days in hospital
Age at death
Himsworth and Goldacre 1999, BMJ 3191338-1339
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The population crisis would be
unmanageable Actually the birth rate is way
below replacement levels in all affluent
societies. Population is falling in all of
Western Europe it is rising in the USA only
because of immigration. Will children continue
to become less popular as wealth increases? No
one knows.
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Replacing brain cells would endanger continuance
of identity Replacing atoms and molecules
doesnt seem to do so -- our cells are doing this
continuously. Why should replacement of a few
cells at a time (also continuously, from stem
cells) be any different? It isnt causing
Parkinsons patients concern....
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• We must say nothing to cause optimism until we
  succeed in mice
• On the contrary -- by then it will probably be
  too late to avert global strife.
• The day it is reported that a two-year-old mouse
  has been rejuvenated by a year by means that are
  accepted (by experts) to be feasibly translatable
  to humans, society at large will realise that the
  defeat of aging is no longer science fiction.
  Their apathy will turn overnight into
  determination to accelerate that advance, but
  also to ensure that they have access to it as
  soon as possible and that they survive until that
  time. This will translate AT ONCE into
• - Near-universal unwillingness to take dangerous
  but socially vital jobs
• Raised expenditure on healthcare, at the expense
  of other goods/services
• Political need to maximise national wealth at
  the expense of other nations
• Biogerontologists thus have a critical social
  duty to prepare policy-makers in time -- NOW!

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Tyrants will reign forever life-extension will
only be for the rich Only if we let it be so.
Given enough advance warning (and conviction that
the warning is for real), policy-makers can and
will formulate the necessary economic and
political reorganisation to avert such problems.
This has happened time and time again throughout
history (constitutions rewritten, minimal health
care institutionalised, etc.) -- though usually
in the aftermath of a major crisis rather than in
advance of it....
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Science only moves on when the old guard
retire Science moves on when the money moves
on. The old guard tend to control the money (via
peer review), but that need not be so. Besides,
some vocal pessimists favour debate This book
... includes discussion of the ethical dilemmas
posed by the possibility of manipulating aging
and delaying death. If we succeed in slowing
aging, we will be confronted with many extremely
difficult decisions, and I believe strongly that
we all need to start considering the consequences
NOW. Hayflick, How and Why We Age (1994)
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Failure will rebound as loss of funding Its
true that this happened to artificial
intelligence research also (less conspicuously)
in other fields. BUT THERE IS A NOTABLE
DIFFERENCE Lack of AI doesnt (overtly) kill
people. Progress against cancer has fallen
hugely short of predictions at the beginning of
the war on cancer, but its funding has not
suffered in the slightest.
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Well be seen as charlatans We do and will
indeed face this risk. But we also risk being
responsible for the deaths of over 100,000 people
every day that ENS is not developed, if we fail
to speak and act to bring it about as soon as
possible. I know which risk I prefer to take.
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Solution 2 the American (and my) way Lets roll
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Proposal an Institute of Biomedical
Gerontology Remit to promote, co-ordinate and
fund the focused development of technologies such
as those I discussed. Motivation Ultimately,
the present sluggishness of progress results from
a vacuum between the basic scientists
(knowledgeable but curiosity-driven) and the
supplement-suckers (goal-directed but
oversimplistic). The key need is to make the
most of those few (so far) people with both the
expertise and the will. This is not absurdly
expensive -- as noted, the balance will be tipped
by progress in mice.