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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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September 20, 2013

Google Versus Aging

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Posted by Derek

If you haven't heard that Google is now funding research into human aging and lifespan, they'll be very disappointed. There's been plenty of publicity, which I find sort of interesting, considering that there's not too much to announce:

The Time article—and a Google blog post released at the same time—provided scant detail about what the new company, called Calico, will actually do. According to Time, the company, to be based somewhere in the Bay Area, will place long-term bets on unspecified technologies that could help fight the diseases of aging.

Page did tell Time he thinks biomedical researchers may have focused on the wrong problems and that health-care companies don’t think long-term enough. “In some industries it takes 10 or 20 years to go from an idea to something being real. Health care is certainly one of those areas,” Page told Time. “We should shoot for the things that are really, really important, so 10 or 20 years from now we have those things done.”

The company’s initial investors are Google and Arthur Levinson, also chairman of Apple’s board and that of biotech company Genentech. Levinson, a trained biochemist, will be the CEO of Calico, which the The New York Times reported is short for California Life Company.

I'm fine with this. Actually, I'm more than fine - I think it's a good idea, and I also think that it's a good idea for the money coming into it to be long-term, patient money, because it's going to have to be. I think that human life span can probably be extended, although no one's ready to say if that's going to mean thirty extra years of being 40, or thirty extra years of being 90. If you know what Trimalchio says about seeing the Cumaean Sybil in the Satyricon, you'll have come across the problem before. (Trimalchio's an unlikely fount of wisdom, but he seems pretty much on target with that one).

Patience will be needed on several fronts. Biochemically, there are actually a number of ideas to follow up on, and while that's good news in general, it also means that there's a lot of work ahead. Not all of these are going to actually extend lifespan, I think it's safe to say, and sorting them out will be a real job. But that's the sort of problem that a lot of therapeutic areas have. Aging research has several others piled on top of it.

One of them it shares with areas like diabetes and cardiovascular disease: you're looking for a drug or therapy that the patient will be taking for the rest of their lives - their extended lives, if all goes well - so toxicology becomes a huge concern. Tiny safety concerns can become big ones over the decades. And that leads into another big issue, the regulatory one. How would one set up a clinical trial for an anti-aging therapy? How long would it run? How long would you have to work with the FDA to get something together? Keep in mind that the agency doesn't have any framework for making people better than normal. You'll note that despite the possible lifespan enhancement with the sirtuin compounds, GSK never really mentioned this possibility in their takeover of Sirtris. It was all about diabetes and other conditions that have defined clinical endpoints and a regulatory environment already in place.

The answer to that problem, then, is surely to pick some disease of aging and see if you can ameliorate it by attacking the aging process in general. It's a bit like a second derivative: in other therapeutic areas, you pick a biomarker, and you try to get approval based on an effect against it as a surrogate for the long-term benefits against the actual disease. In this case, though, you'd pick an actual medical condition, and hope to get approval using it as a surrogate against the meta-disease of aging itself. Those will not be short trials, nor easy to run, nor will it be easy to obtain statistical significance in them.

And I don't think we'll be seeing one of those for quite some time. Larry Page himself is 40, I believe, so if he's looking for a benefit that he might realize, he's almost certainly out of luck. As am I at 51. Page's ten or twenty year timeline seems very short indeed. If I find a wonder drug in my lab this afternoon, it won't be hitting the pharmacy shelves for about fifteen years itself. I hope I'm wrong about this, but I doubt if anything will be worked out enough to try before either of us are much further into old age, at which point you start to run into that Cumaean Sibyl problem. Unless, of course, you are fortunate enough to come up with something that actually turns the clock back a bit, but that's much less likely. Just slowing it down is enough of a feat already. I realize that this is more of my patented brand of "pessimistic optimism", but I can't make myself come up with any other opinion yet.

I thought seriously about titling this post "Gegen Den Tod Ist Kein Kräutlein Gewachsen", but I figured that would drive my traffic into the basement. That is, I'm told, one of the mottos of the old German herbalists, translating as "Against death does no simple grow". It's safe to assume, though, that anything that really does usefully treat aging will not be simple, so the Germans are probably still in the right.

Update: a reader has sent along more information on that quotation. It actually goes back to Latin (cue various readers holding their heads and moaning). It goes ". . .contra vim mortis non est medicamen in hortis", and is part of the declamations that are more or less Quintilian's work on Roman court cases and rhetoric (thus often ascribed to "pseudo-Quintilian").

Comments (85) + TrackBacks (0) | Category: Aging and Lifespan


COMMENTS

1. biotechbaumer on September 20, 2013 8:26 AM writes...

It almost certainly becomes, as you said, a second derivative issue. Many diseases are due to the aging process: CVD, cancer, neurodegeneration. Companies trying to develop drugs against these diseases could equally call themselves anti-aging companies no?

Perhaps the clearest regulatory path forward would be to try to treat an accelerated aging disease such as Progeria. At least the clinical endpoints would be much shorter.

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2. pgwu on September 20, 2013 9:18 AM writes...

Someone young tweeted not long ago saying it sucks when the smartest people in his generation spend their time figuring out how to make more people clicking ad buttons. Would be interesting to see how this is going to change. One VC is proud of not funding startups with people who have PhD degrees, as told by another VC on a blog because "a real entrepreneur would not have the patience to complete a Ph.D.". With attitudes like that, he might as well wait for godot. But big data is going to save us all, according to the gurus.

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3. Sam Weller on September 20, 2013 9:20 AM writes...

I am wondering whether the company will be as focused on drug therapy or biotechnology as your blog suggests. Sure, this can be part of the equation, but isn't it possible that life span can be extended significantly by other means? Nutrition and exercise of course come into mind, but also sleep, body temperature control, etc.

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4. johnnyboy on September 20, 2013 9:22 AM writes...

hmm let's see: a few million californian dollars vs. 3 billion years of evolution - I wonder who will win ?
Seriously, rich folks: why not throw your money at real world, solvable problems ? Like oh, I don't know, multi-drug resistant bacteria maybe ? Or malaria ? Or just clean drinking water ? I'm sure Page and Levinson will find it an amazing accomplishment for humankind if they get to live for 5 years longer, but personally I don't really want to be 90 for 20 years, which is what this surely will amount to, if it does amount to anything.

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5. Anonymous on September 20, 2013 9:43 AM writes...

Well said Johnnyboy, well said indeed

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6. jbosch on September 20, 2013 9:47 AM writes...

A tree when it reaches it's lifespan dies off and new trees are allowed to continue where the old tree was.

Why do we humans think we are irreplaceable or even worth hanging around past our anticipated lifetime ?
Just think about the world population for a minute if we should find something that allows us to even extend our lifespan even more, then resources that are limited become even more limited. And it's obvious from the statistics that people tend to get older in developed nations. This will further split the world in those who have and those that are exploited. Just a different example is growing corn for fuel instead of feeding people. Does anybody care how much the tortilla cost in Mexico for a poor family now ? The price has increased more than triple in the past 5 years.

I honestly think it's waste of money.

We should more focus on treating diseases and allowing everybody (very much including or even focusing on developing nations) to reach the standard of developed nations.

In some countries of the World in the 21st century the average life expectancy is still 40, in Europe and US it's almost double of that.

Just my 2 cents

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7. Curious Wavefunction on September 20, 2013 9:58 AM writes...

Yawn...another day, another ridiculous, sensationalist TIME magazine cover (Remember the "Cure for Cancer" travesty a few months ago?).

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8. jbosch on September 20, 2013 10:00 AM writes...

"Gegen Den Tod Ist Kein Krautlein Gewachsen"

That's actually a pretty good one and hits the nail of the head :-)
But you missed in your translation somewhere the "Kräutlein" which is herb, so there is hope though maybe nature has not herb against death, but you chemist might find something in chemical space :-)

My free translation is:
"No herb has grown against death"

The closest english idiom I can come up with is:
There's no cure for that

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9. Derek Lowe on September 20, 2013 10:08 AM writes...

#8 Jbosch - just got the umlaut back in there, so I go from "little cabbage" (I guess) back to "herb". The translation I offered is from a science fiction novel by James Blish, and "simple", I believe, is an old herbal term for a medicine made from a single plant. Gegen den Tod ist kein Molekül synthesiert?

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10. a. nonymaus on September 20, 2013 10:10 AM writes...

Perhaps they're going to explore how to reduce socioeconomic inequality, which has proven negative effects on lifespan and quality of life.

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11. Anonymous on September 20, 2013 10:25 AM writes...

If these ventures discover something worthwhile, I'm sure that there are ways to make use of it which fall outside the FDA's regulatory frameworks. In any case, an investigatory new drug of exceptional promise needn't be "FDA approved" for people like Mr. Page to take it -- as Sirtris has shown with their off-label sales of Resveratrol, as sports dopers are showing with their (presumed) use of those unapproved PPAR-delta agonists, as ALS-sufferers have shown with their grassroots efforts at obtaining investigational drugs, etc., etc....

As for reducing "socioeconomic inequality" and enriching people in the backwaters of Africa and India... Good luck with that. Seriously. I think that viable anti-aging strategies are more plausible. In any case, it's apples and oranges.

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12. an onymis on September 20, 2013 10:28 AM writes...

a. nonymaus makes a good point. Google might have more luck extending mean life expectancies by treating conditions that lead to death in the relatively young rather than expending all there effort trying to help the very old tack a little more time onto their wheelchair years.

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13. MoMo on September 20, 2013 10:33 AM writes...

Page is arrogant and naive at the same time. Just because he made mega billions with Google doesn't give him any authority to judge the Pharma industry who do not "shoot for things that are really, really important". WTF does he know?

The molecular world and the cyber world are separated by vast degrees of technical issues, and applying whatever philosophy they use at Google is welcomed, but such visionaries will fail and don't hold your breath. The Cyber world is filled with mental toddlers, no fetuses, compared to the thinking needed in medical science.


So plow your money into a "Fountain of Youth" pill Larry, and while you are at it you might as well fund projects to look for Unicorns and Yetis.

You'll have better success with the latter.

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14. Puff the Mutant Dragon on September 20, 2013 10:33 AM writes...

I'm with @4 on this one. Why throw money at aging when there are other problems that need a much more urgent solution (e.g. global warming, malaria, drug-resistant bacteria...the list goes on...)

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15. QOTL on September 20, 2013 10:41 AM writes...

an onymis (#12), I don't have access to the Time story, but this quote from the Atlantic Wire reacap (http://www.theatlanticwire.com/technology/2013/09/google-wants-cheat-death/69570/)
suggest they are thinking along those lines:

"One of the things I thought was amazing is that if you solve cancer, you’d add about three years to people’s average life expectancy," Page told Time. "We think of solving cancer as this huge thing that’ll totally change the world. But when you really take a step back and look at it, yeah, there are many, many tragic cases of cancer, and it’s very, very sad, but in the aggregate, it’s not as big an advance as you might think."

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17. Anonymous on September 20, 2013 11:15 AM writes...

Live longer and you just have many more unproductive years feeding off state pensions and requiring more expensive treatments for diseases like AD. This is insane. They should invent a more effective cancer that strikes at 70, at least that would do some good for the world.

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18. Pig Farmer on September 20, 2013 11:17 AM writes...

I'll cast my lot in with #4 and # 10 as well. There is something rather obscene about throwing all this money at a rich man's first-world pipedream when there are far more pressing problems that would benefit greatly from that investment. I'm 51. I'll be grateful if I reach my mid-eighties (like my grandfather, who by that time had had enough of life). I might be happy with 60 or 70 years more of being 51 (although I can already feel myself going downhill), but another 30 years of being 80 or 90? No thanks.

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19. Johannes on September 20, 2013 11:17 AM writes...

Wont come from small molecules

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20. ellita on September 20, 2013 11:19 AM writes...

Speaking of fighting evolution--I suspect that homo sapiens is probably already much better optimized for long lifespan than other critters. Mice (or worms, for that matter) are optimized for fast reproduction, not long life. All those animal models where you can extend longevity, whether it's by calorie restriction or resveratrol, will probably not work as well or at all in people. But, the media loves this stuff.

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21. NMH on September 20, 2013 11:37 AM writes...

I think we should try to improve healthspan before we try to improve longevity, but I think Page wants longevity because he knows he will probably remain healthy as long as he maintains a good diet, so he wants to live longer; 130 instead of 100 years.

Its just a really rich guy who wants to be immortal, or live a long time. Think Henry Ford.

We dont need fancy drugs for the most massive improvement of healthspan that would be gained simply by eating more like Seventh Day Adventists.

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22. Hap on September 20, 2013 11:40 AM writes...

MoMo: No, nobody really seems to care that much about income inequality (well, other than those who can't or won't do anything about it), but anti-aging drugs don't work well against bombs and bullets. Lots of people with short lives and no money and nothing to lose and a fortunate few with long, relatively happy lifespans (but who depend on the stuff made by the rest) seems like a recipe for the old colonial days at best and endless slaughter at worst.

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23. MDACC Grad on September 20, 2013 11:44 AM writes...

What's the [corporate] point in attempting this when the FDA requires a 20 year trial, your IP lasts 5 years once you start the trial, India compulsory licenses it out in 4 years and China stole it before you even started the trial?

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24. newnickname on September 20, 2013 12:11 PM writes...

@All: I thought that Life Extension was already solved with Buckyballs. I read about it In the Pipeline (April 18, 2012. "Buckyballs Prolong Life? Really?" and several followups, including May 9 and June 12.)!

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25. Vanzetti on September 20, 2013 12:30 PM writes...

ITT: Deathists and their bullshit.

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26. cynical1 on September 20, 2013 1:05 PM writes...

"An optimist is a fellow who believes what's going to be, will be postponed. " (Kin Hubbard)

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27. Pig Farmer on September 20, 2013 1:11 PM writes...

Can't speak for the rest, but I'm not deathist. I just think it's a matter of priorities. There are other problems we ought to address first before extending the life spans of a few very rich people. Otherwise, it's bullets and bombs,just like Hap says. We are many. They are few.

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28. RKN on September 20, 2013 1:16 PM writes...

There has always been push back against bold projects, the funding of which people say would be better spent elsewhere, until years later when the project has completed and these same people applaud all the incidental technologies that were discovered in the course of pursuing the project. Think going to the moon.

I hope similar incidental goodness comes from this latest Google venture, even assuming they fall short of their goal. On the other hand it may just fizzle out. The Bay Area being a place where if you're a "player" and haven't started a new company this week your reputation is in doubt.

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29. Squib on September 20, 2013 2:31 PM writes...

People in the comments always seem to think Big Pharma takes an approach that is too conservative. Everyone is angry that nobody is trying to think "outside the box". However, when something like this happens, you guys all seem to get angry as well. What are you looking for? If Google throws a couple hundred million at whatever problem they're going after then so what? The money is inconsequential to them.

I live in the Bay Area and see their driverless cars every once in a while. They seem to be beating all the traditional auto companies at that. Why not let google try something crazy? The cynicism around here seems to prevail whether its another article about R&D cuts or something going into Phase III that everyone thinks will fail. Why be so cynical about this too?

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30. B on September 20, 2013 2:49 PM writes...

@28 and 29:

The difference with 'the moon' or with 'driverless cars' is that you have a target and you have a set of rigid rules and criteria that you have to fit to make something possible. Getting to the moon was worked out, we just had to know how to do it. The same is with driverless cars.

That IS NOT true with aging and death. We do not fully understand the underlying mechanisms of why we age and what is going on in the ageing process. There are many theories, many of which seem likely but we still don't know the rigid facts of the process. Thus, targeting which we do not fully understand is likely to be frivolous. The same thing is seen time and time again with alzheimer's therapies. We do not understand the mechanism and are left hitting our head against the wall, hoping that will fix the problem.

Until we have the biology of the problem understood, we will not be able to find the answer.

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31. Mr Toad on September 20, 2013 2:50 PM writes...

The abundance of teenage idealism in the comments here is surprising. "solve world hunger/malaria before you invest in extending life span". Are you serious? On this imaginary scale of social justice, probably 90% of businesses should be closed down and every nickel and dime should be spent on feeding the hungry and resolving regional conflicts.

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32. alf on September 20, 2013 2:51 PM writes...

Squib, I completely agree.

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33. why? on September 20, 2013 3:21 PM writes...

Brings to mind a funny rant by Lewis Black on the Daily Show: "mortality is NOT a flaw, its a feature". Healthy lifespan is great but I don't think we need humanity to endure into universal senility.

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34. Hap on September 20, 2013 3:21 PM writes...

Google's got lots of money and they (and their people) can spend it as they want. I certainly can't be claimed to have a surplus of imagination, and maybe they do, and something will come of it.

My assumption, though, is that they're trying to do something for humanity as a whole, and not just for themselves or their friends. In that case, you do probably need to think about what might happen if you succeed. A solution to big problems that presents lots of problems it itself might be a good thing, or it might not. If you mean to good for humanity, then it's important to think about what you're doing, and what kind of world you want to make.

31: We've been trying hard-nosed "everyone for themselves" ideals for about forty years, and it mostly seems to be getting us to Brazil, thirty years ago. Not sure why "teenage idealism" is a worse sin, exactly.

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35. Mr Toad on September 20, 2013 4:06 PM writes...

#34 I don't know how Brazil was 40 years ago, and I think it's besides the point.

We are talking about private money going into a business venture, not charity. If Google decided to invest the money in yet another smartphone or some other gadget or a jet plane, you wouldn't have seen these "save the world first" reactions. While the skepticism (and by extension cynicism) is completely justified from a scientific standpoint, ranking this investment on a moral value scale is irrelevant. Extending life span is not an immoral, and not even an unworthy goal. It may be low on some people's priority, but what about the iPhone6, or the next Airbus jet, or the next Cereal from General Mills? Is it OK to spend money on these luxuries when people are starving to death somewhere?

At the end of the day, this company may go bust, but along the way it will most likely spend a lot of money on research, and some of it will turn out to be useful. Not sure that this blog readers can afford to snub such initiatives.

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36. Hap on September 20, 2013 4:27 PM writes...

Why? Isn't everything you do judgeable on such a scale, or does money make all other issues go away? I'm curious about that, because I've got some appointments at local banks to make if that's true...

If they're trying to make money, they can do what they want, how they want (within the law). (Even then, though, moral questions do and should exist - spending money has consequences, just like other actions, and so what comes of what you buy may be personally and, if you're successful enough, historically relevant.) If they're trying to make things better for people or appear to be doing so (because, unless they're looking for ancillary funding, that would be the likely goal of all of the publicity), then questions of whether what you want to do is likely to make things better for people seem rather pertinent. If you spend money to do good and make harm instead, then you'd have been better off not spending the money at all.

You could also ask whether the exploring on the way to that goal might be more fruitful than explorations to other goals, and that's probably a harder question for anyone to answer (else it wouldn't be research).

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37. Hap on September 20, 2013 4:50 PM writes...

It is also good that someone is thinking long-term and not right now. At least for a lot of the research worth doing in the long term, though, questions of whether the ends are good will come up, whether or not the venture is public or private.

The discussions on obesity here for one might be analogous in some ways. It would be good to have something to lessen the frequency of obesity, but the issues of moral hazard (would we just eat more?) have come into deciding whether to try to find one or not, even in what would be solely for-profit ventures. The need for long-term use of any such agent and the resultant safety bars are probably the bigger issues, but the question of whether such a drug would be a good idea is relevant in any case.

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38. Curious Wavefunction on September 20, 2013 5:18 PM writes...

I think this is an excellent move on Google's part. Irrespective of the specific merits of aging research, I was waiting for the time when Google would do what AT&T did with Bell Labs. Instead of criticizing them let's celebrate the fact that a company which actually has the resources to throw into long-term, blue sky thinking is actually doing something to that effect.