Extending life - on an ever-expanding timetable?

If you happened to see the umpteenth repeat of BBC 4's (peculiar but rather good) comedy/science crossover show It's Only a Theory the other night, you'll have seen the unforgettable figure of the epically-bearded Dr Aubrey de Grey expounding his provocative proposition that the first 1000-year-old human being has probably already been born, due to supposedly imminent breakthroughs in regenerative medicine.  I think the first time I heard of de Grey was a number of years ago when he briefly appeared on an episode of Horizon about the prospects for expanding human lifespan.  I have to say - perhaps due to the way he was edited - he came across on that occasion as rather deranged, comparing the thousands of daily deaths from aging to 9/11, and angrily demanding that something be done to stop the "carnage".  So it was interesting to see him given the time to make his case in a much more measured and logical way.  He doesn't actually claim that the technology that might enable people to live for centuries is just around the corner, but he does suggest that it will be possible within a few decades to extend healthy lifespan by approximately thirty years, and - crucially - that this will buy enough time for further breakthroughs in rejuvenation techniques to be made, which in turn will buy yet more time, and so on.  He calls this process "longevity escape velocity", and it's upon this that he bases his conviction that people currently alive might go on to live unimaginably long lives.

I was sufficiently intrigued by all this a few months ago that I decided to read up on the general subject and see just how far to the fringe de Grey's views actually are within the scientific community.  The answer was slightly surprising.  While (as you might expect) his particular blueprint for the rapid conquest of aging is well beyond the bounds of mainstream thinking, there does seem to be a genuine sense that some kind of breakthrough is forthcoming, with leading experts talking confidently of a more modest seven year increase in healthy lifespan in the foreseeable future.  For the avoidance of doubt, this would not be achieved by the conventional means of tackling specific illnesses, but by genuinely contriving a way in which someone who is, say, chronologically 60 years old, could be biologically a few years younger than that.  So does this mean that the only difference between de Grey and the mainstream scientists is scale of ambition - seven years versus thirty?  Not quite.  There is in fact an almost total divergence of approach, with the majority of scientists in the field working more or less exclusively on the slowing of the aging process, while de Grey intends to reverse it.  His elaborate plan for achieving this ("Strategies for Engineered Negligible Senescence" or "SENS") is, his critics contend, nothing short of pseudo-science, as there is currently no firm evidential basis for believing it will work - in contrast to the possible methods for slowing aging, which have repeatedly shown their promise through laboratory tests on animals.  Dr de Grey counters that his is a goal-directed engineering approach, something which many curiosity-driven scientists simply cannot understand.  He cites as an example the Wright Brothers, who in the design and construction phase had no way of knowing for sure that their flying machine would work - but if they'd needed that certainty to proceed, they'd never have bothered trying to work towards their goal in the first place.

So it's a kind of theological dispute, but one that matters immensely, because the believers in each approach are in competition for funds and credibility.  Some - although not all - of the mainstream biogerontologists are furious with de Grey, believing his high-profile promotion of what they see as "quackery" is hindering their own chances of progress.  As a non-scientist, I'm clearly in no position to judge if they're right about the unscientific nature of de Grey's ideas, but having read some of his papers and interviews from the last few years, one very simple thing does repeatedly leap out and bug me.  He always seems to state exactly the same timescale for 'longevity escape velocity' - that there is a 50/50 chance of proof-of-concept in mice within ten years, and of the first therapies being available to humans within 25 years.  Clearly, with seven years or so having elapsed since he started making this claim, those numbers should have come down accordingly - instead, they have remained absolutely static.  With no real trace of an explanation for this, the claimed timescale does start to look suspiciously like a sleight-of-hand, solely designed to grab public attention.

Anyway, I'd heard that de Grey was reasonably approachable and might respond to emails, so a few weeks ago I decided to chance my arm and go to the horse's mouth with my concerns.  I think I was also slightly hoping I might get a rare Scot Goes Pop 'exclusive' out of it!  In the end one of his research assistants was kind enough to send me a long and detailed response which, while repeatedly slipping into sales patter, does to be fair address the points I had raised in a very full and frank way -

Hi James,
My name is Michael Rae; I'm one of Dr. de Grey's research assistants, and coauthor of his recent book, "Ending Aging"

(This is the new, paperback edition, which has an Afterword covering some of the advances in SENS science that were made after the publication of the hardcover).

With all of his duties in research, promoting engineering-based biotechnologies to arrest and reverse biological aging, and the promotion the book, Dr. de Grey has for some time been unable to keep up with most of his correspondence; when he received your email, he asked me to send his apologies, and answer your question as best I can.

You wrote:
> I've
> recently read a lot about your work on aging, and while I'm
> obviously not in a position to judge for myself the scientific
> plausibility of your ideas, there is one simple problem that leaps
> out at me (and I'm sure many others) about the credibility of your
> claims.
>
> In every article and interview I've seen going back to at least
> 2003, you've given exactly the same estimated timescale - a 50/50
> chance of robust mouse rejuvenation within ten years, and of the
> first therapies being available for humans within 25 years.  But if
> you'd been right about that in 2003, we should of course by now be
> just three years away from proof of concept in mice, and eighteen
> years away from the human breakthrough.
>
> Perhaps what you really mean is that there would be a 50/50 chance
> of meeting these ambitious timescales IF the $1 billion you need
> magically became available right now?

In fact, that's exactly what it means: we could well be as little as 25 years away from the goal *once we get started* . So far, unfortunately, the world has not begun to push for it. While SENS Foundation is doing the greatest amount of leveraged, critical-path work that we can on our limited research budget, and while most of the challenges that need to be tackled for achieving comprehensive rejuvenation are being funded and pursued to one degree or another by government and industry research, still there is nowhere near the level of intense, single-minded commitment worldwide required to achieve this goal.

> If so, that puts a completely
> different complexion on things, because - for better or worse - that
> scale of investment is surely not going to be forthcoming in
> anything close to the foreseeable future, and the chances of hitting
> those timescales in the real world is therefore not 50/50, but
> essentially zero.

Wow, and I thought I was a pessimist! But the idea that there is NO chance that this scale of investment could be forthcoming strikes even me as entirely unreasonable. The 2010 Haiti earthquake got commitments of US$3.3 bn to help out 3 million victims; the 2004 Indian Ocean tsunami  got commitments nearly twice that; and to use an hackneyed example, the TARP fund is catechismally invoked as the "$700 bn bailout."

Right now, there are 100,000 people dying of aging worldwide every single day, and many times this number needlessly sliding further down the progressive slide of age-related disease, disability, dependence, and dementia. $1 bn (or several times this) per year is a pittance, even within biomedical research: the NIH got US$$30.5B for FY. 2009, for goodness' sake!

But of course, that doesn't mean it's inevitable, or easy to mobilize. Surely you didn't think that Dr. de Grey was saying that we could all sit on our butts, and business-as-usual would give even odds of human rejuvenation in a quarter century.

> Or, if that's not the case, was there some other factor that was
> holding back the progress of research in 2003 or 2006 that doesn't
> apply now?

It still applies now: it's simply funding, and proactive refocusing of biomedical research and (soon thereafter) some regulatory tweaks.

> I suppose what I'm really asking is this : doesn't it
> seem overwhelmingly likely to you that in 2015 or 2020, you'll still
> be giving media interviews in which you're saying "we could be just
> ten years away from doing this in mice, and 25 years away in humans"?

Overwhelmingly, no -- but very possible in 2015, and plausible in 2020.

So what are you going to do about it >:) ?

If you're ready to help us to hasten progress in SENS science, we have quite a few listed here:

http://sens.org/help-us/volunteer

Also, you can pick up a copy of Aubrey's and my book (link above) and, after having read it for your own further understanding, get the word out by passing your copy around to others you know, and/or by donating it to a library, and/or by picking up extra copies for the latter 2 purposes.

Another one: have you checked out _Rejuvenation Research_ ("an international, interdisciplinary, peer-reviewed academic journal that covers all aspects of biology and biomedicine relevant to the combating, and ultimately the reversal, of age-related physiological and cognitive decline in nonhuman species and eventually in humans"), of which Dr. de Grey is Editor-in-Chief)? If you're a student or academic, and your institution has a subscription, you should be able to get direct online access -- and if it doesn't, you can recommend it here:

http://www.liebertpub.com/library.aspx?pub_id=127

This would not only give you access to the journal, but would help to disseminate its high-quality biogerontological research at your institution. You would need to get your library's contact info, preferably for the collections department; these are usually available on the 'contact' page, or one can ask a librarian about the right person to contact about a subscription recommendation.

And (naked plug!) remember that you can help to ensure that real age-reversing biotechnology becomes available as soon as possible, alleviating the most age-related suffering and death, by making a donation to support SENS research:

http://sens.org/donate

I leave it to you to choose how you will take on the moral and scientific challenge of biological aging. However you proceed: live long -- live young!

-Michael

So many thanks to Michael for taking the time to respond so thoroughly.  While he clearly genuinely feels there are more grounds for optimism on the funding front than I can conceive of, I do still think Dr de Grey should be fronting up about that crucial caveat to a much greater extent when speaking to the media.  And to address Michael's question (ie. did I really think de Grey was saying his 25-year timescale was in no way contingent on some fairly dramatic changes in thinking on the part of policy-makers) - well, whatever I may have thought, frankly I do believe that is the misleading impression he has been leaving his audience with on many occasions. As for my own "contribution", since I'm not actually a student, nor an academic, nor a millionaire, I think writing this post will probably have to do to be getting on with!