We’re tackling aging
calicolabs.com
calicolabs.com
"Geriatrics is one of the lower-paid medical specialties, in part because virtually all its patients are on Medicare, which pays doctors less than commercial insurers." Source: http://newoldage.blogs.nytimes.com/2013/01/09/even-fewer-ger...
The Scumbag 2nd law of thermodynamics is a really harsh mistress (Solved ageing? Die of cancer anyway etc.).
But hey, the digerati elite are showing touches of grey and most of them wouldn't have any better use for their money anyway once they've got the mansion, the yacht, the jet, and the mistress(es) half their age.
What happens when we get good at treating dementia?
(Obviously, "good at treating" is with respect to what went before, not where we want to be.)
What happens when we get good at treating dementia is that your children will be able to have intelligent conversations with their great great grandparents (or you will be able to have intelligent conversations with your great great grandchildren).
Every time a cell divides, it has a chance of turning malignant. Live long enough and one of those cells will win the cancer lottery and take you down if you don't catch it in time. Many forms of cancer are symptom-free long enough for this to happen (pancreatic for example) and we do not yet have the technology to easily detect this until it's late in the game.
And that's just one way to go. Then there are aneurisms and all sorts of other odd bodily defects that will eventually manifest.
Ageing is tough. That said, eat right, exercise, and get enough sleep, and you'll stand the best chance to max out your time clock.
Anyway, some people like to work on tough problems. No one said it's going to be easy or that progress won't come slowly. There are 7 billion people on the planet. If you can help with early detection of pancreatic cancer, for example, you will impact many lives.
I had to squint and blow up the screen. Then I scrolled down a bit to get a better view and it was gone.
First, I have been to a conference a year ago when the researcher claimed to have restored senescent cells back to a "young" state. This kind of things completely bypasses any "programmed to die" scheme, and gives hope for actual biological immortality.
Second, I call the future you outlined a "Hansonian dystopia", with rich people running at a faster rate than poorer people, and mass duplication/murder in the name of productivity. I'd rather avoid those drawbacks.
Third, if we ever get to full blown mind uploading, we will probably have de-novo AI to contend with, and the intelligence explosion that it will likely imply. At this point, we can throw out just everything we know about economics and politics, and pray the AI is programmed for our own good (lest it turns Skynet and kills us all in 5 seconds —if we're lucky).
Oh, and one last thing: backup is already an option right now: it's called cryonics. It's not exactly reliable (no one has been revived yet), but that's a genuine cause for hope (unlike joining your hands and look up the sky).
2. Right, having attained technological immortality, rich people could completely isolate themselves from the poor, getting richer and richer (in the broad sense of the word - more experienced, more advanced in studies, etc) and poor would lose even the theoretical path into this "rich bubble". You can't "rather avoid the drawbacks" by stopping progress, you'll have to use the progress to avoid drawbacks, but I do not see how.
Cryonics is not a backup. Backup implies working restore procedure. Cryonics is like removing platters from the hard drive with a screwdriver and putting them into file cabinet somewhere in someone's basement, hoping that they would be just okay. Yeah, possible.
(Those interested in guessing what is more likely to happen may be interested by the Yudkowsky-Hanson debate.)
Cryonics: agreed. I wouldn't bet my life on it if I could help it. Cryonicists often say that cryonics is the second worst thing that can happen to you (just after certain death).
Why? Because IBM's so-called "neuro-chips" are actually just specialized hardware for running Spiking Neural Networks, AFAICT. They have jack-all to do with brain uploading.
Now stop drooling.
Is it a long term strategy to increase the age of humanity so they search more, use more of android, and earn Google more revenue because their search business is saturating? or is there a truly altruistic motive behind funding Calico? Seeing on their website an executive with title VP of Business Development seems interesting and just wonder how would he benefit Google through Calico's business.
People died to make room for Larry. For him to try and cheat the system when it's his turn is the ultimate act of disrespect. So no, that isn't good enough.
They probably wouldn't have chosen to do so if they had a choice. Larry, and others working on this problem, want to give people a choice in the matter.
I'm extremely interested in understanding your perspective. See, I not only publicly support this, but as an aging researcher, I spend my days, nights, and weekends (right now, in fact) working towards this goal.
I do so because I believe that, in a world full of Bad Things, death is pretty unambiguously the worst of them. Every time someone dies, a wealth of unique life experience and personality is lost, permanently. Forget Larry, I don't want to see my friends, family, and neighbors die. I don't know you at all, but I don't want you to die. And yes, I don't want to die myself either.
If you think that extending life is selfish and wrong, then to be logically consistent, wouldn't the Red Cross and hospitals and so on be evil organizations? What principle could we possibly use to establish when someone's life has been "too long"?
- Every time a person dies, their life is passed on through those they have connected with and influenced. Their influence on the world does not end, only their opportunity to see its effect. And most importantly, gives room for someone to do even more with what they have accomplished.
> death is pretty unambiguously the worst of them.
- Death may be better described as one of the scariest of them. When you are dead you feel no pain. You don't even know you are dead. Certainly, we miss those in our life who have passed away, but they live on in our hearts and dreams for the remainder of our lives.
> I don't know you at all, but I don't want you to die. And yes, I don't want to die myself either.
- I'm sure most people don't want to die. That's part of what makes life so important. What makes us try to make every moment count. There is so much life someone can live in 65 years. Do we really need more?
> What principle could we possibly use to establish when someone's life has been "too long"?
- When you start to try and reverse or disable aging as opposed to attempting to cure disease.
I don't want to invalidate your work, but are you sure we really need this as a society? Or maybe we instead need to focus on making the time we have better for everyone?
I agree that traces of people remain after their death -- genetically, in their children, and in the memories of those who knew them. But those traces fade quickly, and for all but the most famous, virtually disappear in a few centuries. And surely you agree that a memory is a poor substitute for a person -- I'd rather be able to talk to my dad or neighbor than have even the fondest memories of them.
We both seem to agree that improving the quality of people's lives, as well as the quantity, is extremely important. Aging is far from the only problem society faces. Tackling inequality/poverty, political dysfunction, war, ignorance, and other problems are also extremely important goals, and I greatly respect people who work on them. I also recognize that curing aging will introduce new societal problems even as it solves others (e.g., rising health care costs).
I think where we differ is that I think these other problems can be solved as well, and I believe that curing aging will, on balance help society more than it harms it. Consider how our scientific progress is retarded when our best scientists die or lose their mental acuity later in life. I've already alluded to the fact that people seem to ignore problems ranging from global warming to the national debt because "I'll be dead before it becomes a problem."
I have several responses to your concern that if people stop aging, we won't have room for future generations. First, it is well known that wealthier people and countries have a lower birth rate, so by solving poverty, the birth rate will decrease. Second, even if people don't age, they can still die from accidents or disease. Also, I think eventually humanity will expand to the stars, although we are far from it now.
Massive societal change is coming, from many sources, whether or not aging is solved (although I make no claims about when). Technology is going to put many people out of work. AI will eventually be created. Methods will be developed to improve human intelligence, enhancing technological development but increasing wealth inequality. Even if none of these developments occur, there is still an increasing centralization of wealth and power in developed countries.
It is hard to know how curing aging would interact with these trends, except to say that I think people would be more circumspect about societal decisions if they knew they would have to bear the long-term consequences. I think the demand for religion would decrease, which would have positive effects on geopolitical stability. Living longer would also give people more time to get educated, which would help with the electoral ignorance that is at the root of so many problems in the US.
Finally, your proposed principle for determining the "correct" lifespan is not a new one:
> When you start to try and reverse or disable aging as opposed to attempting to cure disease.
The NIH takes a similar view. The problem is that almost all major diseases (diabetes, heart disease, neurodegenerative disease, to some extent cancer) are all diseases of aging. Young people don't (usually) get them. It may well be that to "cure" these diseases, we will have to solve the underlying problem -- that is, aging.
Also, consider that it is just genetic happenstance that our species max lifespan happens to be 120. Why should it not be 15 or 60 or 240? Letting evolution decide our lifespan is certainly the simplest method, but it seems fairly arbitrary.
As for passing on to others. Its not memories or genetics. It's inertia. As we go through life we set other things in motion. Our interactions with each other and the world around us causes changes in direction and speed. Everything we do sets something else into motion, infinitely unique from what would have happened without us. No matter how small the action.
Are you implying that their life is not passed on as long as they don't die? I mean, dead or no, the influence is there.
The way I see it, I don't pass my life on when I die. I pass by life on as long as I live. When I die, I stop passing my life on.
> There is so much life someone can live in 65 years. Do we really need more?
I don't know what I need, but I certainly want more. And so does everyone else, as far as I can tell. Why go against everyone's will?
From the paper Demographic Consequences of Defeating Aging.
'Moreover, if some members of society reject to use new anti-aging technologies for some religious or any other reasons (inconvenience, non-compliance, fear of side effects, costs, etc.), then the total population size may even decrease over time. Thus, even in the case of the most radical life extension scenario, population growth could be relatively slow and may not necessarily lead to overpopulation. Therefore, the real concerns should be placed not on the threat of catastrophic population consequences (overpopulation), but rather on such potential obstacles to a success of biomedical war on aging, as scientific, organizational, and financial limitations.'
Full paper: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3192186/
"640K ought to be enough for anybody." -Bill Gates
Just like when people found better uses for space, people will find better uses for longer lifelines, given the opportunity. Considering how quickly we advance, how much more informed we are, how much more control we have over our lives, and how much increasingly more there is to do in the world for everyone, it makes sense now more than ever.
Other technologies can furthermore make this even more convenient, and possibly even eliminate the trade-off of having less children. The dynamics currently in place were intended for a different world, and the one of today is changing very rapidly.
Can't you just replace 65 with 55 and say the same thing? 55 with 45? 45 with 35?
Conversely, if I can live through so much life in 65 years, couldn't I live through more in 75? 85? 95? Given n years of healthy, productive life, at what point does the n+1th year of healthy productive life give you a negative marginal value?
And yet so very little life we actually do live in our limited time! Most of our time on this Earth is spent in drudgery just trying to stay alive.
>Or maybe we instead need to focus on making the time we have better for everyone?
We ought to be doing both. Anti-aging treatments ought to be available universally, for absolutely everyone, just like all other health-care that saves your life.
We also ought to be getting rid of things like poverty, that kill people a bit more slowly and make them live in misery in the meantime. And toil, too, while we're at it: it's simply got to go.
Unfortunately, our society seems to take no account whatsoever of ought, so anti-aging didn't happen until some billionaire decided he liked transhumanist scifi novels.
Just like AI, people have been trying for a long time. It's just a damn hard problem.
Those few have been studied heavily in aging, but trying to extrapolate differences in these organisms to humans is very challenging because they have totally different anatomies, genomes, and sets of proteins. Plus, lifespan is very multifactorial; for example, you can "extend lifespan" in many species by inhibiting cancer, but that isn't really stopping aging per se.
It's hard for many reasons, but I think the most important one is that we have no good mathematical or experimental tools for understanding and predicting how a given perturbation (drug, diet, etc) will affect a hugely complex network of 25K+ transcripts. Or how those transcripts affect each other causally. In a variety of tissues. And genetic backgrounds. And in the context of longer-term changes like epigenetic changes and DNA mutation.
Another huge problem is that lifespan studies take, well, lifetimes. So we usually do them in organisms like worms and flies, which are very different from humans.
On the other hand, it can still tick me off how aging and anti-aging are, in much of the world, simply not considered medical issues worthy of research at all.
But we have learned to deal with it. Instead of saying you're studying aging, you say you're studying "age-associated disease X" (which works for almost any X) and the effects of age on X. Or you say, "rising health care costs are a huge problem, and the bulk of costs are in the elderly. Therefore, we want to find ways to reduce age-associated morbidity and thereby lower costs."
Transparent ploys, but they work fairly well.
I honestly hadn't thought that this isn't a genuine good argument in favor of anti-aging research.
Luckily, there are also people like you, who choose to do something about it. Personally, I work on AI, so that hopefully IBM Watson in 2050 will be able to help us cure aging.
When I was considering careers, I concluded that there are 3 world-changing scientific problems: aging, neuroscience (understanding the brain and cognitive enhancement), and AI. Interestingly, they're all intertwined.
Best of luck. Personally I think AI will come before a cure for aging. In some ways, I view my work as a fallback, in case AI doesn't come fast enough.
The societal stakes for AI are also much higher.
Excuse me, I'm as anti-death as anyone else, but I'm going to laugh bitterly now. Don't ask why.
There are lots of things worse than death.
There's plenty of space in the universe.
And yeah future generations will be looking at us how we act because they definitely would prefer living here imo.
http://www.zdnet.com/googles-life-extension-venture-is-part-...
I suppose it's the Khruschev strategy for winning the platform and talent wars – "we will bury you!"
Genetics is hot, and it is easy to raise funds for nowadays. See the launch of Venter's Human Longevity Inc, for example. But I see this in connection with work on longevity as looking for the keys under the lamp, because that is where the light is, not because it is where you are likely to obtain results. The comparative genetics of human longevity should be irrelevant to work on aging: we all age because of the occurrence of the same forms of cellular and molecular damage. Outside of rare mutations, genetics has nothing to do with that - the same damage happens to everyone. The target should be repair of that damage, not trying to expensively slightly slow the pace at which it arrives.
That the metabolic manipulation approach to treating aging has such popularity despite the lack of results is a mystery. The other way, the repair approach, has the same lack of results - but that is because next to no money is heading in that direction. We have the early demonstration that targeted removal of senescent cells extends life in accelerated aging mice [1], for example, and ample reason to believe it is beneficial for ordinary individuals, but it took philanthropic funding to move that research forward at all. Institutions want to see standard issue drug development and manipulation of metabolism because it is the mainstream of medicine and the expected thing: the round peg for the round hole of regulation. This has nothing at all to do with whether it is the best path forward.
This all further points to the fact that if we want to see meaningful results in longevity science, measured in years of health gained for people who are already old, then we need to produce results that demonstrate the futility of the mainstream path taken by Google, the sirtuin researchers, and Human Longevity Inc, etc, and deonstrate that repair approaches can do far more for far less money. The senescent cell targeting is probably the closest work to that point.
Based on what I've seen of Calico to date, I'm expecting it to be a more publicized version of the Ellison Medical Foundation as an initiative: an extension of work already taking place at the NIA and in companies like Human Longevity Inc, and something that fails to step outside that box. It will produce general benefits in terms of data and knowledge, and absolutely fail to meaningfully extend human life. This will continue until someone changes the approach to this work to focus on repair of the causes of aging [2] rather than metabolic tinkering to slow aging. The latter is a slow road to marginal end results that can do next to nothing to help the people who grew old waiting for them to arrive.
[0]: https://www.fightaging.org/archives/2013/10/advocating-the-l...
[1]: http://dx.doi.org/10.1038/nature10600
[2]: http://www.sens.org/research/introduction-to-sens-research
Yes, genetics is hot, but also necessary to find the molecular drivers of the aging process. Despite what de Grey and others might have us believe, it is very far from clear what age-associated molecular changes qualify as "damage". Which changes are causal and which are compensatory? Are the widespread changes in DNA methylation and other epigenomic markers that occur with age "damage"? AFAIK, no one knows.
Even when it is clear that a molecular change can probably be considered "damage" (loss of telomeres, DNA damage, protein aggregation), it is still unclear which kinds of damage actually need to be reversed to promote longevity.
I think it is silly to see SENS and Calico et al as if they were in competition. We are all working towards the same goal, and anyone who claims to know for certain which avenue will ultimately attain our common goal of achieving increased longevity is selling you a load.
EDIT: My personal opinion about the difficulty of funding the SENS program (which I'll take your word for; I don't know anything about their funding sources or situation), is the extravagant claims that have been made. Reviewers don't like those. A lot of scientists have very ambitious and grand goals, but one of the secrets to grant-writing is to frame your goals as ambitious enough to be interesting, but limited enough to be attainable in the 3-5 year scope of a grant. And "unlimited human lifespan" is just a tad too ambitious.
Judging a company just based on a web site. Also the company is still very young that it should be given time to prove itself.
mindless contrarianism
I personally thought the above comment provided detail and references as to why this a tough nut to crack as well as what the current promising approaches may be.
And yes, the company should be given time to prove itself.
But given that they are well-funded, and that their public face is their web site, I would think (and maybe I'm crazy) that they could provide something more interesting than a bunch of vanilla executive bios. This is an amazing area of research and this is the best they can show for it? Not impressed (so far).
Yes, it could be seen as "If Calico hasn't even invested the time and energy necessary to build a decent and informative web presence, they're obviously not serious about what they're doing."
... but it could also be seen as "If Calico hasn't been concerned about their website, maybe that's because they're concerned about other things and have made the decision that the benefit they'd get from a website isn't worth the administrative overhead."
Given that a fanboy is an uncritical true believer and a shill is paid to claim an opinion that they otherwise do not hold, the two terms would seem to be largely incompatible.
I don't really agree with all of what he's saying either, but at least address the content...
I'm a comp. bio. PhD student so don't think this isn't a topic of interest to me, but the answer to every age related topic just isn't "here's a link to some sens promotional material". SENS has some fringe ideas and was mostly rejected by scientists as silly and founded by a charlatan, now Peter Thiel has shown an interest it's got a kind of misappropriated authenticity among those with no scientific background.
It's fair to say OP is a SENS enthusiast. But, as a fellow researcher, you know that there are always differences of opinion about what avenues will be more or less fruitful in a field. That's OK, time will tell.
Personally, I'm not certain whether SENS' fundamental position -- that we should focus on engineering solutions to damage rather than identifying causes -- is correct, but it seems at least a coherent argument. Suppose OP is right: that we are wasting too much money on one rather than another. It would be a real problem, with real consequences: lives lost, and so on. Worth debating, at least.
What could be more amazing than transcending death?
How about transcending our own desires to control nature. Maybe learning to leave things be? That would be a real feat.
Exactly the same argument applies here.
That's actually not a feat at all. There's no grander harmony of nature that needs to be preserved by killing people off at a fixed age. Hell, there never was: we evolved, suffered an ice age, drove the large land mammals to extinction, and emerged from an ice age, all before even inventing writing or agriculture.
Nature is the cruelest thing in the world.
No it isn't, otherwise you wouldn't get things like hydra or the immortal jellyfish. Even lobsters appear to die through predation rather than through aging.
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Of course it isn't. It isn't slashdot either. Just make the point without unnecessary references. Or at minimum use an original reference rather than one I see appearing every 5 pages on HN. Or better still how about just a silent downvote rather than appearing a content prune?
As children, we have billions of neurons more than we do when we reach adulthood and everyday after that we loose something like 10k neurons a day.
Which is a scare because as people age, they become more rigid in general perspectives and beliefs. Its already hard enough bringing about change such as accepting gay people into our society and avoiding wars waged by old bitter people.
As you mature, specially through puberty, you experiment with many different personalities. You gauge your environment and try to figure out the type of person that will be most successful in your environment. All of these personalities are represented by competing neural networks especially in your prefrontal cortex.
But obviously exploring different personalities, characteristics, ambitions, and developing different interests has to slowly be focused and narrowed into something that you can pursue with full confidence. Biologically, this is one of the reasons that when you loose a neuron you don't ever get it back. And the growing age till just after puberty is the fasted period in which your brain sheds neurons that pertain to competing networks that don't pan out as well. There after, neuronal loss averages out to a steady constant but a rate which contributes to a fairly significant loss of the number of neurons for todays life expectancy.
Now if it wasn't already immediately obvious to you, the number of neurons is very directly correlated with intelligence. It isn't the only factor but it definitely is a hugely important factor in terms of capacity of intelligence.
> But the worst idiocy is thinking whatever age you are is superior to any other.
I must say, that perhaps an even worse idiocy is when someone quickly reads something and responds brashly without actually bothering to think.
It isn't a matter of superiority. Its a matter of evolution. Certain advantages rest with certain age groups. Yes is a fact that the capacity for a young adult absorb completely new material is very likely higher than someone of a much older senior. However, a much older senior has the advantage of experience which allows him her to gauge new material as something worth wasting time over.
But as cultures evolve, as philosophies change, age (and by "age" I hope I've already made clear that I'm referring to effects of age on total neuronal loss) makes it difficult to change at the same pace. Do you think its just chance that a younger person brought up with the same strong cultural exposure as his/her equivalent senior end up having much easier time accepting new cultures, ideas, peoples?
Just because you believe "people of all ages can be stupid and ignorant and pigheaded and whatever negative you want to throw out" doesn't address the serious problem of needing to understand how the brain ages. Its biological fact that neuronal cells, unlike other cells in your body, ARE NOT replaced by new neurons (though there is some evidence of very slow neurgensis in various parts of the brain). And its important for you to understand why that is because its servers a very important function. Biology didn't anticipate such long life expectancy on its discourse of evolution.
> I'm sorry people's attitudes aren't boolean they are floating point.
What on gods green earth are you on about there?