Thursday, September 23, 2010

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!

6 comments:

  1. Aubrey has always made it clear that funding is the key and it must be frustrating that many people just can't seem to see it the way he and I do.

    Regardless there are various routes being pursued that will eventually achieve the goal of radical life extension. Personally I am very confident that the SENS project will come to fruition ultimately and that Aubrey de Grey is very much on the right track. Aubrey's theory that if we intervened and removed some of the damage we would make a person biologically younger certainly makes sense. The vital thing is that if it were to turn out that the Aubrey de Grey theory was wrong (or partially wrong) or that we had overlooked something vital then great promise is still beckoning as he acknowledges himself via other breakthroughs in biotechnology and nanotechnology. I am confident that the biotec revolution will yield significant increases in lifespan regardless, the key factor is that Aubrey's role is vital because he is the catalyst that is driving things forward and encouraging people in unrelated fields to work together. I cover quite a lot of areas regarding Aubrey de Grey and other people and organisations involved in combating aging on one of my websites at http://drjohnty.com/

    I am inclined to think that we will be pretty much able to treat and manage aging by 2030. I feel a cure for aging is probably 100 years or more away but repairing the damage caused by aging and thereby making a person biologically younger is probably between 20 and 30 years off.

    A forecast on my website at the bottom of the following page http://drjohnty.com/Exponential_Growth.html that we would introduce the first compounds to slow the aging process into the market between 2015 - 2020 would seem pretty much on target. in 2008 I foresaw a medication that delays aging and buys an extra 7 years or more of healthy lifespan. I should say at this point that I consider drugs which simply slow aging are essentially a dead end in the long term (so I basically agree with Aubrey) but in the short term they are a potential lifeboat because they will enable some older people to survive long enough until the later therapies arrive.

    In wrapping up I must say tne thing that never fails to amaze me is Aubrey's focus and determination to succeed. Personally I feel that if anyone can pull scientists together from all these different areas of research and end up saving 100,000 lives per day it is Dr Aubrey de Grey. You can check out the latest information at http://www.sens.org/

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  2. Aubrey has always made it clear that funding is the key and it must be frustrating that many people just can't seem to see the wood for the trees. I annoys me so it must be totally maddening to Aubrey.

    I am inclined to think that we will be pretty much able to treat and manage aging by 2030. I feel a cure for aging is probably 100 years or more away but repairing the damage caused by aging and thereby making a person biologically younger is probably between 20 and 30 years off.

    A forecast on my website at the bottom of the following page http://drjohnty.com/Exponential_Growth.html that we would introduce the first compounds to slow the aging process into the market between 2015 - 2020 would seem pretty much on target. in 2008 I foresaw a medication that delays aging and buys an extra 7 years or more of healthy lifespan. I should say at this point that I consider drugs which simply slow aging are essentially a dead end in the long term (so I basically agree with Aubrey) but in the short term they are a potential lifeboat because they will enable some older people to survive long enough until the later therapies arrive.

    In wrapping up I must say tne thing that never fails to amaze me is Aubrey's focus and determination to succeed. Personally I feel that if anyone can pull scientists together from all these different areas of research and end up saving 100,000 lives per day it is Dr Aubrey de Grey. You can check out the latest information at http://www.sens.org/

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  3. Thanks for your comments, Dr Johnty. From the little I know of nanotechnology, I can see how that would hold great promise in this area, but surely those kind of breakthroughs must be a very long way away?

    To clarify what I said in my post a bit further, I think what troubles me about Aubrey de Grey's discussion of timetables is this. To be fair, he does very occasionally slip in the phrase "if we get sufficient funding", which would indeed make you think "OK, the 10/25 year forecasts only apply from the hypothetical point at which he has $1 billion to play with". But, much more frequently, he points out that research into many of the relevant areas is being carried out anyway, and that the role of SENS Foundation is simply to "fill in the gaps" and ensure that nothing gets neglected. So I think that would make a lot of reasonable people conclude that, to use Michael's phrase, we have already very much "got started", and therefore the timetables are meant to apply from right now - which would make the fact that they have remained static for seven years (and presumably will remain static for quite some time yet) more than a little puzzling.

    If Michael is implying that the definition of "getting started" is that $1 billion must be pumped into the "single-minded" goal of SENS (if not into SENS Foundation itself), it's very hard to see many grounds for optimism in the near future. From what I can gather, in the several years Aubrey has been at this he has amassed a few million in donations - that is indeed testament to his great passion and determination, but all the same you'd have to be a super-optimist to imagine that he's just about to turn up literally a hundred times as much cash as he has managed through all his immense efforts so far.

    For what it's worth, though, I do wish him well - his basic proposition that the most effective way to tackle the terrible illnesses of old age is to do something about aging itself does seem to be a sound one, and from what I can gather is fully shared even by the leading biogerontologists who dismiss the SENS approach.

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  4. Clearly, it is quite hard to forecast exactly when nanotechnology will start to play a significant role in treating age related decline. Nanotechnology is already appearing in items such as cosmetics and sunscreen as well as playing an increasingly important role in medicine, as it develops aided by the miniaturization of computerized delivery, diagnostic and monitoring systems it will unquestionably have very far-reaching implications. Although currently in an early stage of development Nanotechnology is already forming the basis for highly innovative drug delivery systems. In my opinion current research will lead to breakthroughs in a whole range of areas but funding is clearly concentrating on the detection, treatment and diagnosis of many types of cancer although radical progress should be made in a wide variety of areas within the next 10-20 years. Clearly actually creating nanobots is currently well beyond our present technology but progress in technology is exponential as I show on my website at http://drjohnty.com/Exponential_Growth.html and if you look at where we were around 30 years ago and then look 30 years ahead it does not seem quite so inconceivable we would have vastly enhanced capabilities within that timeframe. Below I show where we have moved in the 32 years since 1978, I anticipate a much more significant rate of progress by 2040.

    1978: First test tube baby is born

    1978: Spreadsheet

    1984: DNA fingerprinting

    1985: Vodafone makes the UK's first mobile cell phone call

    1990: World Wide Web

    1996: Dolly the Sheep (first clone)

    1998: Viagra

    2001: Self-contained artificial heart

    2001: First human / machine neural connection - Kevin Warwick

    2003: Hybrid Car

    2003 Human Genome Project (HGP) Completed

    2009: A new computer interface called the sixth sense

    2009: Rapamycin proven to slow aging in a mammal

    2009: A retinal implant for the blind

    2010: First Artificial Pancreas enters human trials

    2010: proof that he can turn any adult cell into a completely rejuvenated stem cell

    What has become apparent is that Nanotechnology is already moving from passive to active applications and the new targeted drug therapies involving this technology are already proven to have far fewer side effects with much better outcomes than conventional treatments.

    We have already seen this year that a combination of nanotechnology and adult stem cells has can remove atherosclerosis in the hearts of pigs. This research when combined with stem cells led to new blood vessel growth and the restoration of arterial function, according to the study reported by the American Heart Association see http://www.newsroom.heart.org/index.php?s=43&item=1087

    I think this all indicates we are progressing quite well and Nanotechnology is going to become a cornerstone of rejuvenative medicine.

    I am pretty confident that in less than 10 years we will see the first compound in at least stage II human trials (or maybe evan brought to market) that influences the aging process. Rapamcycin provided the evidence we can extend life in a mammal and a derivative is likely to be a potential life extension drug, but maybe one that adversely effects long-term memory, regardless we must be pretty close because we are clearly on the right track and once we get a foot in the door just as with aircraft, computers, the industrial revolution and other fundamental breakthroughs progress will be very rapid.

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  5. This is Dr. de Grey. Thanks to you both. All I would offer in my defence is that I do in fact insert "subject to funding" into my replies to questions on timeframes much more often than is apparent, but journalists just leave it out (rather as they insist on describing my goals as "immortality" and so on). My view is that progress in the past seven years or so since I started making these timeframe predctions probably amounts to about two years of the progress I thik we would have made with full funding, so it's not as bad as all that.

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  6. Thanks for your comment, Aubrey, that's a very useful clarification. And I do fully appreciate the difficulties of dealing with journalists - I recall the absurd extremes the newspapers used to swing back and forth between over the BSE scare, in spite of the best efforts of scientists to emphasise the high degree of uncertainty.

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