Part 1
Aubrey De Grey AMA
SENS Foundation
(0:27) What specific progress have you made over the past five years? How have your research priorities changed over that time? Are there any ideas that you held close to your heart that subsequent research has overturned? Have you uncovered anything that particularly surprised you in light of your previous research?
SENS foundation has made really encouraging, really dramatic progress over the past five years. We of course work on the very most difficult parts of the SENS panel of applying regenerative medicine to aging, the parts that are at the earliest stage and therefore at the greatest risk of being neglected by other people. And a great example is our work on the elimination of the molecular garbage that accumulates inside cells as byproducts of metabolism. This is something that causes cardiovascular disease. And just recently we published a paper in which we were the first people to show that introducing a bacterial enzyme into human cells in culture can protect them very powerfully against the accumulation and toxicity of the number one toxin in atherosclerosis. Of course, other areas of the SENS panel that other people are pursuing independently of us have also made great progress. So all in all, I’m enormously encouraged. And in terms of changes in what I think is going to happen and what I think could happen, really the only things that have occurred have been good news changes. Cases where people have discovered new shortcuts that make something even easier than we previously thought it was. The rate of progress that we’re seeing is really pretty much what I would have expected overall given the level of funding that’s available, though I know that it could have gone faster and could go faster in the future if that funding is elevated.
(2:08) What about stem cell research? When can we expect to have fully developed artificially made organs such as the heart, lung, or liver? Is there going to be any advancement in brain regeneration in the near future?
Stem cell research and the whole idea of tissue engineering, which is of course one application of stem cell research in a way, is an area that’s probably moving faster than any other in regenerative medicine. Essentially, what we’re seeing at the moment is really dramatic progress in a couple of particular techniques that were only really introduced a few years ago and which are already moving so fast that within a decade I would expect them to overtake traditional organ replacement by transplantation. Those techniques are firstly decellularizing an organ, taking the cells away and just leaving its vasculature and then repopulating that vasculature with new cells. This is a way of avoiding the problems of immune rejection that have of course been the major difficulty of normal organ transplantation since it was first developed. And the second technique being organ printing. The creation using just inkjet printers, using material – biological material laid down one layer at a time. Just in the same way we are seeing 3D printers for non-biological things. These things have been moving so fast that I’m really optimistic about how dramatically they’re going to revolutionize regenerative medicine over the next decade. With regard to the brain of course we can’t look at wholesale replacement of the brain all in one go – that would rather defeat the object. But we can certainly look at stem cell therapies to replace cells that have died and that have of course not been automatically been replaced by the division of other cells. And that’s also moving forward really rapidly with new ways to introduce cells in a way that they’ll migrate around the brain starting from the point where we inject them, and also with ways to remove molecular garbage that accumulates in the brain in diseases like Alzheimer’s.
(4:21) Restoring the pluripotency of somatic cells is very problematic, and pluripotency reversion is a very recent discovery, but it is necessary for your “WILT” approach to defeating cancer. Do you really think it would be possible to develop a cost-efficient industrial process for stem-cell production, in the time-span that you have estimated necessary for the completion of your project?
I’m extremely optimistic about how soon we’re going to see pluripotent stem cells produced from differentiated cell by this de-differentiation concept reaching the clinic. And I’m not the only person who’s optimistic about this. That’s why there are companies like BioTime out there in the private sector pursuing this. Of course in the private sector we normally only see things pursued on a relative short time frame compared to academia. So that’s another testament to that optimism. Really what we’re seeing is not only improvements to the simplicity of the technologies with which we can create embryonic-like stem cells starting from differentiated cells, but also we’re seeing improvements in the quality of those cells, in the extent to which their epigenetic memory, as it’s called, can be really thoroughly erased. So this is moving extremely fast.
(5:18) Has there been progress in verifying your theory of mitochondrial DNA damage?
There’s been some progress in confirming this theory. One of the most heretical – or unorthodox – components of my proposal back in 1997, was that mitochondrial destruction, that happens automatically, ongoingly in cells, is actually a selective process where certain mitochondria are destroyed and other ones are not. Whereas, most people used to think that is was a random process where mitochondria are chosen completely without any, any particular criteria. And, it’s now known that I was right, that this process is selective. Furthermore, the mechanism of that selectivity is now looking as though probably it’s due to changes, chemical changes to the membranes of mitochondria, which again is what I proposed back in 1997. So things are looking good for this theory. However there have been some interesting surprises, for example we now know that mutations in mitochondrial DNA accumulate in stem cells, which is certainly not something that I would have expected back then. However, I do want to emphasize one final point, which is that just like the rest of SENS, the approach that we’re looking at to actually combat the accumulation of mitochondrial mutations does not depend on any particular mechanistic model of how those mutations accumulate in the first place. In this case it involves making those mutations harmless by putting suitably modified copies of the mitochondrial DNA into the nuclear DNA. This is an ambitious project, but the point is that once it works, it doesn’t matter how the mitochondrial mutations got there in the first place.
Part 2
(7:01) Around what principles have you organized your current diet?
I believe that there’s only really one general principle that one can use when it comes to diet or indeed supplements or anything that we can do today to postpone age-related ill health. And that principle is simply to pay attention to your body. The reason I say that is just because people differ from each other so much. So any specific generalization that one might make, like you can have more of this particular vitamin or whatever, is bound to have a variable effect on different people and in some cases it may actually do harm, in some cases it will be no good, and so on. I do want to emphasize though, that unless you’re an unlucky person who’s aging unusually rapidly, I’m pretty sure that there’s nothing that we have around today that can substantially postpone the ill health of old age. And therefore that what we must rely on in order to maximize our chances of having a healthy old age, is simply to hasten the development of therapies that don’t yet exist. Which is exactly what SENS foundation does.
(8:14) In a choice between cybernetic enhancements and technological body modification versus a series of drug supplements and pill as a means of enhancing lifespan, which do you see as being the better option down the road as research and development continues on each?
Well first of all I want to emphasize that really that’s not the right choice, because I’m sure that the ways in which we will really succeed in substantially postponing the ill health of old age, is not by pills and supplements really, or at least not mainly, it will mainly be by regenerative medicine, repairing the molecular and cellular damage that accumulates throughout life. But if we ask a slightly more general question, about the contrast between the promise of biomedical, biological based approaches to combating aging, and shall we say, non-biological approaches, then I think we can predict with some confidence that there will be a progressive improvement, an increase, in the contribution from the non-biological side. What we see at the moment are things like glasses and cochlear implants and moving towards things like artificial hearts, but I think as we see more and more miniaturization, there’s going to be more and more scope for other applications of non-biological technologies to medical problems in general and aging in particular.
(9:31) If you could offer some advice to an upcoming aging researcher, what would it be? Keep in mind that many of us also focus on psycho-social and policy-based aspects of aging as well.
The advice I give to up-and-coming researchers depends very much on what stage one is at. So at the undergraduate level, my advice is to do as general a biology education as possible. The idea here is that aging affects the biology of human beings and other organisms at every level of organization, and therefore it’s no good to just be a biochemist or just a geneticist, you really got to know about all aspects of biology. At the PhD level, I think the critical thing is one’s learning how to cope with the frustration of research, the fact that there will almost always be long periods of time when one’s experiments just aren’t working, or when one finds that one’s last six months of work have been useless or whatever, and so the key thing is to work on something you find really really fascinating, that is going to help you just psychologically to get through those low points in the process. At the postdoctoral level, I think that actually what matters most is to have as much autonomy and to be able to do something that you’re going to get credit for. And so I actually favor going into relatively young labs with a young starting-up professor, who perhaps doesn’t have many other people in their entourage yet. That’s probably the place to get the most done. In terms of the psychosocial and policy aspects, I think what I would say, especially at these more senior levels, at the postdoctoral level especially, that the key thing to do – and this is true on the biology side as well – is to minimize the extent to which one is duplicating or just you know reinforcing and confirming other people’s work. And to focus on areas that tend to be neglected. So in the case of social policy and psychosocial stuff, I think a lot of this revolves around looking at the longer term, looking at how the world is likely to manage with a greater ability to intervene against aging, what the implications are socially and politically and so on. Of course that’s not to say that the current problems of the elderly are in any way unimportant, but I think we already have a great deal of research in that area and perhaps the more forward-looking stuff is more neglected.
(11:58) One of the key concepts you discuss in your talks is escape velocity (that we will reach a stage when life expectancy comes to increase by more than one year for every year that passes). How do you square this with the suggestion that the current generation will enjoy significantly extended lifetimes?
I think it’s a really good example of how extrapolation just doesn’t always work. You know, if you asked someone in 1900 how long it would take to cross the Atlantic in 1950 and they looked at the rates of progress in the increasing speed of ocean-going liners, they wouldn’t have come to an answer of less than a day. Right? So yes, it’s all about new technologies. The thing is, that at the moment when all we have against the ill health and consequent of course mortality of old age is piecemeal one-disease-at-a-time approaches that address the symptoms of aging rather than the causes, it’s inevitable that progress is going to be rather slow. Even though, let’s be clear, progress has been a lot faster than it was a few hundred years ago, we certainly weren’t managing one year per decade back then. But once we can not only slow down but repair the accumulating molecular and cellular damage that we incur throughout life, and that only causes ill health late in life, then we’ll be actually turning back the clock. And turning back the clock buys time to improve therapy so that we can turn back the clock more thoroughly in due course and so on. And this is how I ended up realizing that we were very likely to move pretty much instantaneously – well almost instantaneously – from a point of where we are now, of going up by a couple of years per decade, to a point where we are pushing ill health of old age into the future faster that time is passing. It’s all about new technology and the nature of that new technology.
Part 3
(13:46) Can you address the viability of current cryonics techniques (vitrification) and whether or not companies like Alcor should enjoy continued operations?
So SENS foundation does not work on cryonics, of course, we’re interested in helping people avoid the need to be cryopreserved by fixing them up and repairing their bodies so that they maintain youth while their heart is still beating. However, it’s reasonable to regard resuscitation of a cryopreserved individual as a natural extension of that repair process. Therefore I actually am very positive about the eventual future of cryonics and I’m certainly very interested in it. I would say that at the moment, the situation, the prospects for cryopreservation and the revival of people cryopreserved with the best technology that exist today, are pretty good. The most serious problem that used to exist, until maybe ten years ago, which was the problem of crystallization caused by taking someone down to a temperature below freezing, has now been comprehensively solved with the development of cryoprotectants that can achieve complete vitrification, that is to say, turning the body into a glass rather than into a crystalline solid. There are problems that remain, including the toxicity of these cryoprotectants, and the fracturing that occurs as a result of simple thermal stress, but these problems too are succumbing pretty rapidly to research. So I think even for those that are perhaps a little less optimistic than myself about the revivability of people who are cryopreserved today, we can look forward only a little way down the road at a decade or two or three to cryopreservation techniques that really are going to work really well. Of course everything is going to change enormously when we see a mouse actually revived having been at liquid nitrogen temperatures. And that’s not going to happen tomorrow. But I certainly think that Alcor and Cryonics Institute and the other cryonics organizations are doing sterling work and I support them strongly.
(15:51) What unconventional things should I be doing now (I’m 26) to extend my life to hitherto unreachable levels?
Really the biggest thing you can do, and this is true at any age, is to work to make it conventional to support the defeat of aging with medicine. Make it conventional! And what I mean by that, is any number of different types of things, it could be working on the relevant biomedical research so as to make it look more realistic because what has already been done, it could be advocacy in the media, you know writing as a journalist about this, it could be organizing conferences, there’s all manner of different ways to do advocacy. But really the thing is that if you don’t do that, if you just focus on diet and lifestyle and such like, then you will only make a minimal difference. Whereas if you if you work to hasten the development of therapies that really defeat aging, you can make a big difference. And here’s the key: not just for yourself, but also for an amazing number of other people. An absolutely incalculable number of other people. This is really why I focus on all of this. Another thing is of course that people can do is to invest in companies that are working in this area, or to donate to nonprofits that are working in this area. I would say that the donation to nonprofits is the most urgent, because once something’s gone far enough to attract investors, it generally attracts a lot of investors. And so one’s going to make more of a difference by donating to nonprofits that are working on the earlier stages of all of this, such as of course SENS Foundation.
(17:32) For those that wish to join your field, what areas of study are the most relevant? What would be a good Grad School path for people who want to become researchers in the aging biology and regenerative medicine fields, and which Grad Schools are considered top with regards to aging research?
The thing about grad school, and actually about everything beyond grad school in scientific research, is that you’re more or less required to be a very narrowly focused researcher, and to actually just focus on one very small thing. And in aging of course, there is an enormous amount going wrong, so there is an enormous number of different fields. What makes the situation even harder for an incoming grad student to analyze, is that many of the fields that are relevant to the biomedical defeat of aging are not normally classified as coming under gerontology. In fact the whole of the SENS concept comes from the merging of gerontology with expertise from regenerative medicine and other areas, even as far afield as environmental decontamination. So we’re talking about a very very broad area. I think therefor, the best way for an incoming grad student to choose which area to work in is, well first of all, to get a nicely comprehensive understanding of where the SENS program currently is, so start with my book Ending Aging for example, as a summary, and of course look at the SENS.org website and the publications in the peer-reviewed literature that we’re sponsoring. And then, to get a feel for which areas are most fascinating, which areas one feels one has the most talent to actually pursue. Certainly do not be guided by things that call themselves gerontology because that will artificially restrict you before you’ve even started making the choice.
(19:15) For those of us who didn’t study science or engineering at university, how can we help/contribute/get involved?
There’s really a one-word answer to this question that really encompasses everything. And the word is advocacy. Advocacy simply means educating and reassuring people about the prospect of medically defeating aging and about what it could mean for humanity. I use education very advisedly here, because ultimately when I talk to people who have concerns, whatever those concerns may be, about the defeat of aging with medicine, and who are ambivalent as a result about whether we should be pursuing that task as quickly as possible, I normally find that their concerns come down to misunderstandings of one sort or another. Either about the nature of the therapy and you know, what it would actually do in terms of extending healthy life rather than extending the undesirable frail part of life. About what it would do in terms of the economy, people think it would be terribly expensive and therefore might increase inequality, whereas in fact the truth is that this would pay for itself in society extremely rapidly and therefore it’s definitely going to be made universally available, people are worried about sociological and environmental consequences arising from the prospect of overpopulation, but again it seems very clear that that’s not going to happen because of the trends that we’re already seeing in terms of birth rates and in terms of age that women have their children on average. You know, all of these things are simply a matter of giving people the right information. But in order to do that, of course, first of all you need to educate yourself. I actually quite often find that our most ardent supporters who just ‘get it’ and just don’t feel that there’s any reason to worry about these things, have not always educated themselves very well, and so they don’t always give the most persuasive, and the most important, the most useful answer to people who come to them with a contrary view. It’s all about advocacy.
Part 4 (Last one, I swear)
Part 4
(21:21) Do you think the patent system and intellectual property regime in the West fosters innovation and helps get SENS closer to its goals, or is it a hindrance?
I think that the for-profit sector and the nonprofit sector both have important roles to play in hastening as much as possible the development of these therapies. I’m absolutely sure that it’s good to attract people of all persuasions into this field to give their effort and their money to make these things happen, and that certainly includes people who prefer to invest money, for profit, for an exit strategy which of course tends to depend on intellectual property and patents, just as much as people who are coming in as philanthropists. So I’m certainly not in favor of any radical overhaul of the IP system or the patent system as a route to making this happen, I think where we are at the moment is pretty much ok.
(22:15) We’ve already started reading about cutting-edge treatments in the laboratory: the deletion of senescent cells that you linked to on your website, DRACO/Panacea at Lincoln Labs at MIT, all manner of stem cell treatments… When do you expect commercial treatments to become available?
It’s important to remember that there is a wide disparity, a wide spectrum of the extent to which the various components of SENS have actually already proceeded. Some of them are at a level where they make sense commercially already. So let’s take an example of the elimination of amyloid from the brain of Alzheimer’s patients. That’s something that I would probably say is the number one simplest and most far advanced component of SENS, and sure enough it’s now in phase 3 clinical trials, those trials are being orchestrated by a company, in south San Francisco at Elan Pharmaceuticals. The stem cell world is another case where this is all happening, where there is a number of companies, a burgeoning number of companies in this space, many of them working in areas of stem cell therapies that are highly relevant to the defeat of aging. There are other areas of course, the areas that SENS Foundation tends to focus most on, which are at an earlier stage of development, and it may be a little while before those things actually get to a point where they can be commercialized realistically. However, one mustn’t be too pessimistic about that. The particular case that was mentioned in the question about the elimination of senescent cells, has actually already led to a very significant, nearly ten million dollars I understand, investment in a startup company being pursued by the researchers who published this paper only 6 months ago. And that’s despite the fact that the paper was just a study in mice, and it was not a study indicating any particular route towards the discovery of a drug that could actually achieve the same medical result. So you know, one has reasons to be very optimistic about the private sector’s involvement in all of this.
(23:59) How would you feel about a /r/SENS subreddit?
I think it would be great to have a greater presence on Reddit. I certainly think that we need in general, to improve our web presence and our social media presence at SENS foundation, and we are in the process of allocating more resources to doing exactly that. I certainly think that Reddit’s a fine example of where we should have a greater presence.
Thank you Reddit!
Filmed and Edited by Daniel Finfer for SENS Foundation 2012
Visit www.sens.org for more information.
Music by Ancient Lasers
www.ancientlasers.com
Transcribed by Scott Shambaugh
The upvotes already indicate this, but I thought I should explicitly point out that transcribing videos like this is a massive service, and I for one think you're awesome for doing it.
Thank you! It feels good to know that other people appreciate the work I put into this. I don't have a main account on lesswrong, so this karma is as sweet as ever.
Transcribing this 25 min video took about 2 hours over the course of a plane flight, which isn't that long and I feel is a good use of time.
That said, I was disheartened by the response back on /r/IAMA - it seems that people were not nearly as interested in the response as the chance to ask questions. I would say that if people are seriously about advocacy (which you should be, it's the best way to funnel funding to critically important projects like this), we find a way to do it that is far sweeter and more consumable than a 25 minute video.
You should tell them to link to the transcript from the video, or at least leave a comment to that effect.
Watch the video response here: http://www.youtube.com/watch?v=-tsI_28O3Ws
This was posted here on lesswrong a while ago, but they recently uploaded a new version of the video and I took the liberty of typing up a transcript.
The video is fairly long, about 25 minutes. But it's incredibly engaging and I highly recommend watching it. For those who prefer text (because it's faster or because you are a computer), you can read the transcript in this google doc, or below in the comments. Enjoy!