[xaa]

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]

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/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/

[xaa]

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]

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/ (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-...

[xaa]

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]

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/ 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.

[xaa]

> nobody really reads that many papers

That is very true. Nowadays, a good day for me is 3. We're too busy writing papers, writing grants, writing code, answering e-mails, filling out forms, or whatever. But I work at an institute that does a lot besides aging. I don't get the impression this is specific to the aging field.

But on the other hand, the truth is that most papers do not have very much relevant information in them. There are millions of papers published per year. Aging is so interdisciplinary it would be foolish to think that if you just read J. Gerontology (now "GeroScience" lol, that was done to suck up to Felippe Sierra), Aging Cell, and a few others, you'll be caught up.

That's why I went to the data. Even IF a human could read them all, most of the interesting data nowadays is high-throughput and is analyzed in the most shallow way within the text. The real beef is deposited in GEO or SRA.

I am inclined to think that biology works in a way that is not very comprehensible to the human mind. For example, when humans design a system, it's modular, and you try to minimize the number of interdependencies between modules.

In biology, it seems almost everything affects everything else, to the point that if someone publishes a paper saying "X upregulates Y", I find it almost irrelevant; they have, assuming everything was done correctly, characterized one edge in a very highly connected network. Probably the "X upregulates Y" is contextual as well.

I don't know the solution to all this. I just wanted to do this as a career, and as a graduate student we very clearly learned that there are certain lines we need to color within if we wanted to be paid to do research.

[industromatic]

This mention triggered 30 visits to the blog post in the last 1.5 days. Next time I make a blog.kitmatic.com progress post, I'll mention it here also. Busy working on the 3D carved electronics safety enclosure. Using FreeCAD 3D is tough lately because the devs have made tons of change without new docs for it, but it means culture shock's design is OSHWA certified reusable in new designs.

[skrebbel]

Just wondering, if you "have some funding for crazy gene therapy projets", what does that mean? Where does "outside funding" usually come from? I imagine Larry Ellison flying you over in his private jet and saying "kanzure, I want to live longer, here's some cash please make it happen". Is it like that?

[kanzure]

Yes, it's exactly like that.

.... Eliezer leaned back in his chair. "Mr. Musk, what can I do for you?". The two engaged in a blissful staredown as their eyes locked. After several overbearing teary-eyed moments, Elon replied with a simple request. "World peace." And thus began a long, unproductive partnership between Big Yud and Peter Thiel-- I mean, Elon Musk -- a partnership focused not on the practical realities of actually building relevant transhumanist technology, but rather a venture focused on theories of world peace-- er, I mean, friendliness-- and writing fanfic instead of executing on important engineering/lab skills to achieve technological goals.

This story continued here: https://www.youtube.com/watch?v=nXARrMadTKk

More seriously... Some projects don't really require that much funding to happen. Often you can use specialized knowledge to forego otherwise hugely expensive efforts. It mostly starts with skill and knowledge, not money. As an example, trying out random CRISPR-Cas9 projects can actually be really cheap, less than $5k/project if the projects are structured just right. The trick is to pick projects that happen to be within budget and interesting enough to everyone involved. And if there needs to be a larger budget, sometimes the project is interesting enough to attract outsider funding.

[rsynnott]

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), it doesn't seem interesting as a routine procedure, even if rejection isn't an issue.

[FeepingCreature]

Higher demand does mean more funding to develop an economy of scale.