4 ms·

Obviously this article is full of self-modification for fairly whimsical reasons. It's easy to make fun of. But this kind of problem is more serious and discou

by xaa 9y ago

Obviously this article is full of self-modification for fairly whimsical reasons. It's easy to make fun of. But this kind of problem is more serious and discouraging when you think about aging. You know cells in each organ are going to mutate, get protein aggregation, fibrosis, and so on. Instead of trying to figure out something to do about each of those things individually at the molecular level, it might seem simpler to just replace organs periodically. Every 20 years, just get a new heart, etc. Nontrivial and risky, of course, but perhaps less so than the even less-developed alternatives. But as TFA points out, surgery is hard on the body, and the body likes to reject transplants, be they biological or mechanical. Integrating vasculature is hard, integrating nerves is REALLY hard. So in short, I think even if these particular applications are frivolous, hopefully people who are doing this will help push forward knowledge on the general question of "how do you add/replace/integrate body parts safely and robustly". They are truly pioneers, in all senses of the term -- they're pushing forward the frontier at great personal risk.

kanzure 9y ago
Replacing organs (for now) is a task that often involves immunosuppression. Perhaps it will be possible to work around this with techniques like gene therapy + xenotransplantation: http://diyhpl.us/wiki/transcripts/hgp-write/2016-05-10/transplantation/ http://diyhpl.us/wiki/transcripts/hgp-write/2016-05-10/trans... In the mean time, there's also some work that can be done on the the anti-aging front by picking very simple mutations that cause delayed aging phenotypes (skip to "longevity" section): http://diyhpl.us/wiki/genetic-modifications/ http://diyhpl.us/wiki/genetic-modifications/
- xaa 9y ago
  I work in aging research. A very nice set of notes you have there. The field is not really thinking in this direction. By "picking" mutations, I suppose you mean gene therapy. As you probably know, NIA does not consider aging a disease, just a risk factor for other diseases. So we cannot possibly test anything remotely risky in humans for the treatment of aging, and that certainly includes both transplants and gene therapy. We have to backdoor our way in via stuff like Alzheimer's, dementia, sarcopenia, etc, and it seems unlikely that most gene therapy interventions that target aging per se would have enough efficacy on that kind of disease to justify the risk. They are too advanced already. Even so, this is the kind of thing I think about while driving to work, frustrated at the slow pace that occurs while working within the system :) I am inclined to agree that the problems with transplantation, both biological and mechanical, are mostly solvable though. I think the kinks will have to be worked out in other fields where prosthetics, surgery, and gene therapy have a better perceived risk/reward ratio than aging.
  - kanzure 9y ago
    Well dude, I have some funding for crazy gene therapy projects, so let me know if you want to work on things that matter. But it's all somewhat outside of academia, so it doesn't really appeal to everyone. Some very high-level background on where this is coming from: http://diyhpl.us/wiki/hplusroadmap/ http://diyhpl.us/wiki/hplusroadmap/ (we hang out mostly on IRC and would love to hear your project ideas). Much more modest in scope, this is one of our recent projects: https://blog.kitmatic.com/2017/06/28/electroporation-is-now-quick-high-yield-and-commodity-priced/ https://blog.kitmatic.com/2017/06/28/electroporation-is-now-...
    - xaa 9y ago
      That sounds interesting. This is a really busy period but within the next few weeks I hope to check it out. In general, I love meeting with the non-academic side of this work. I met de Grey and some of his associates at last year's AAA meeting. The relationship is complicated, as you know. I see the value in both types of research -- people working outside the system don't have to worry about IRBs, paper-writing, etc, and can take risks we can't. OTOH, there are a lot of very smart people on the inside who are working on "things that matter". For example, Jim Kirkland and senolytics. They have access to expertise, funding, samples, and personnel that the non-academic community cannot realistically match. Although the entrance of Calico et al is a new quantity and it will be interesting to see how that turns out. As a very short summary of my focus, I came into the field, read a lot of papers, and came to the conclusion "no one knows what causes aging". So my focus is on bioinformatics systems to process a lot of data and help me figure out what direction should be most fruitful to focus on. I work with wet-lab people but don't do it myself. I hope the new generation of academic aging researchers will reach out more to the non-academic side more, though. I plan to do so.
      - kanzure 9y ago
        After a conference once, Aubrey sat down with me at whatever bar we were at, and he told me that one of the dirty little secrets about the field of aging research is that nobody really reads that many papers. I laughed it off, I thought he was pulling a fast one on me. At the time I was intentionally reading about 10 papers/day ( http://diyhpl.us/~bryan/papers2/longevity/ http://diyhpl.us/~bryan/papers2/longevity/ not all of them on longevity, of course). I told him my personal target, and he basically said nope, other people are reading at most a few papers per month. I don't really think the academic system is working :-). Biology is crazy complex, there's just no way for anyone to get enough context if they are just grazing around.
rsynnott 9y ago
Where were you planning on getting all these organs, though? There's a shortage now, even though transplantation is an unpleasant last resort; unless xenotransplantation is sorted out or we go full Niven (https://en.m.wikipedia.org/wiki/A_Gift_From_Earth https://en.m.wikipedia.org/wiki/A_Gift_From_Earth), it doesn't seem interesting as a routine procedure, even if rejection isn't an issue.
- FeepingCreature 9y ago
  Higher demand does mean more funding to develop an economy of scale.

by xaa 9y ago

kanzure 9y ago

Replacing organs (for now) is a task that often involves immunosuppression. Perhaps it will be possible to work around this with techniques like gene therapy + xenotransplantation: http://diyhpl.us/wiki/transcripts/hgp-write/2016-05-10/transplantation/ http://diyhpl.us/wiki/transcripts/hgp-write/2016-05-10/trans... In the mean time, there's also some work that can be done on the the anti-aging front by picking very simple mutations that cause delayed aging phenotypes (skip to "longevity" section): http://diyhpl.us/wiki/genetic-modifications/ http://diyhpl.us/wiki/genetic-modifications/

xaa 9y ago
I work in aging research. A very nice set of notes you have there. The field is not really thinking in this direction. By "picking" mutations, I suppose you mean gene therapy. As you probably know, NIA does not consider aging a disease, just a risk factor for other diseases. So we cannot possibly test anything remotely risky in humans for the treatment of aging, and that certainly includes both transplants and gene therapy. We have to backdoor our way in via stuff like Alzheimer's, dementia, sarcopenia, etc, and it seems unlikely that most gene therapy interventions that target aging per se would have enough efficacy on that kind of disease to justify the risk. They are too advanced already. Even so, this is the kind of thing I think about while driving to work, frustrated at the slow pace that occurs while working within the system :) I am inclined to agree that the problems with transplantation, both biological and mechanical, are mostly solvable though. I think the kinks will have to be worked out in other fields where prosthetics, surgery, and gene therapy have a better perceived risk/reward ratio than aging.
- kanzure 9y ago
  Well dude, I have some funding for crazy gene therapy projects, so let me know if you want to work on things that matter. But it's all somewhat outside of academia, so it doesn't really appeal to everyone. Some very high-level background on where this is coming from: http://diyhpl.us/wiki/hplusroadmap/ http://diyhpl.us/wiki/hplusroadmap/ (we hang out mostly on IRC and would love to hear your project ideas). Much more modest in scope, this is one of our recent projects: https://blog.kitmatic.com/2017/06/28/electroporation-is-now-quick-high-yield-and-commodity-priced/ https://blog.kitmatic.com/2017/06/28/electroporation-is-now-...
  - xaa 9y ago
    That sounds interesting. This is a really busy period but within the next few weeks I hope to check it out. In general, I love meeting with the non-academic side of this work. I met de Grey and some of his associates at last year's AAA meeting. The relationship is complicated, as you know. I see the value in both types of research -- people working outside the system don't have to worry about IRBs, paper-writing, etc, and can take risks we can't. OTOH, there are a lot of very smart people on the inside who are working on "things that matter". For example, Jim Kirkland and senolytics. They have access to expertise, funding, samples, and personnel that the non-academic community cannot realistically match. Although the entrance of Calico et al is a new quantity and it will be interesting to see how that turns out. As a very short summary of my focus, I came into the field, read a lot of papers, and came to the conclusion "no one knows what causes aging". So my focus is on bioinformatics systems to process a lot of data and help me figure out what direction should be most fruitful to focus on. I work with wet-lab people but don't do it myself. I hope the new generation of academic aging researchers will reach out more to the non-academic side more, though. I plan to do so.
    - kanzure 9y ago
      After a conference once, Aubrey sat down with me at whatever bar we were at, and he told me that one of the dirty little secrets about the field of aging research is that nobody really reads that many papers. I laughed it off, I thought he was pulling a fast one on me. At the time I was intentionally reading about 10 papers/day ( http://diyhpl.us/~bryan/papers2/longevity/ http://diyhpl.us/~bryan/papers2/longevity/ not all of them on longevity, of course). I told him my personal target, and he basically said nope, other people are reading at most a few papers per month. I don't really think the academic system is working :-). Biology is crazy complex, there's just no way for anyone to get enough context if they are just grazing around.

rsynnott 9y ago

Where were you planning on getting all these organs, though? There's a shortage now, even though transplantation is an unpleasant last resort; unless xenotransplantation is sorted out or we go full Niven (https://en.m.wikipedia.org/wiki/A_Gift_From_Earth https://en.m.wikipedia.org/wiki/A_Gift_From_Earth), it doesn't seem interesting as a routine procedure, even if rejection isn't an issue.

FeepingCreature 9y ago
Higher demand does mean more funding to develop an economy of scale.