The Mythical Merits of Mealy-Mouthed Messaging: Part Two
Posted by Jeriaska on August 23rd, 2007
The central goal of Aubrey de Grey’s work is to expedite the development of a true cure for human aging. As a scientist with a training in an engineering discipline (computer science), he believes himself to be well placed to bridge this gap. Continued from “The Mythical Merits of Mealy-Mouthed Messaging: Part One.”
The following transcript of Aubrey de Grey’s 2007 Transvision presentation “The Mythical Merits of Mealy-Mouthed Messaging” has been corrected and approved by the author.
The Mythical Merits of Mealy-Mouthed Messaging: Part Two
So here’s the good news. Now on this graph I am showing a bunch of cohorts, that is to say, groups of people of different ages. Specifically, these are groups of people who are certain ages at the time that the first of the scheduled therapies arrives. And this is the measure of how rapidly they arrive thereafter. So the top line is what happens in this simulation when the cohorts are already 80 years-old. At that point most people have got 70% of the amount of damage that will kill them outright immediately. There’s a threshold there. So, they are not going to die immediately, but they are at high risk of death from small challenges, like catching flu, or whatever. And eventually that damage starts coming down as the therapies start to repair damage faster than the damage is being laid down. So, those few people who might survive and get over the hump, so to speak, become increasingly protected from age-related causes of death as time goes on.
The second line down here, the pale blue line, is a cohort that is only ten years younger, 70 years-old, when the first therapies arrive. As you can see, they don’t get nearly so high up before the therapies start to be overall beneficial. What does that mean in terms of survival? The black line represents the natural distribution of ages at death (of any cohort) when there are no therapies applied at any age. And, as you can see, the blue line, which is the oldest cohort from the previous graph, does not benefit very much, simply because these people, though they have a non-zero probability of surviving through the bad times, that probability multiplied up year after year through the period when they are very frail is sufficiently high that basically nobody gets through. A few people get a few years, and that’s it. But the second cohort, that were only ten years younger, remember, 10% of them get through to the point where damage has been reduced to a level that will essentially kill nobody.
Now, essentially these graphs only represent death from age-related causes. If we introduce death from age-independent causes then there would still be a small slope on each of these lines. But death from age-dependent causes would go away. And if we look at the cohort that was 60 years-old when the therapies were first introduced, then half of them survive. So, this was the kind of thing that I had intuitively always felt: that there would be a very sharp cusp there between making the cut and not making the cut. But now we have a much more sophisticated in silico reinforcement of that intuition.
So, that’s really pretty good news. And this is in press at the moment, I should point out. It will come out in a very well respected journal, a gerontology journal, the Journal of the American Aging Association. I’m not sure exactly when, but it will come out probably before the end of the year. So, I’m hoping that will certainly make a big difference to the credibility, and make it very much more difficult at least for mainstream gerontologists to persist in their arguments from personal incredulity.
Now this simulation has so far only been used for the sort of trajectory of therapies that I described on the graph similar to the one on the screen now, a few slides ago. But we can equally use it for more sophisticated variations on the same theme. Here, for example, I’m showing what would happen if the first therapies that come along were to fix half the damage, but the second therapies when they come along 20 years later, or whenever, they don’t fix half of the previously unfixable damage, they only fix a third of it. And the third time they only fix a quarter of the remaining damage, and so on. As you can see, that’s still good enough, which is awfully good news. Because otherwise, someone might come along and say, ‘Yes, well, that’s all very well. We might indeed be able to exceed life extension escape velocity and have the doublings of the therapies every thirty years or whatever, for awhile. But there’s going to come a time when we get a really bad century, where we just don’t make any progress. And you’re all going to die. So, what’s the point?’ Arguably enough, there’s plenty of point anyway. This is just to show that that’s not going to happen, probably. It will be easier and easier to stay ahead of the curve, as time goes on.
Here is an example of that in the real world. Vintage cars are of course many times older than they were ever designed to be. And they are still going. They are still working just as well as they did when they rolled off the production line. Of course they are old fashioned, but they are not old in the sense that this is how they were built. The question is, How much work is being done to keep these machines in good condition? And the answer is, Lots – but, not appreciably more than was being done let’s say 30 or 50 years ago when these cars were only three, or four, or five times as old as they were ever designed to be. The message here is that we have got to the point with classic cars where the longevity escape velocity, the rate at which the sophistication of maintenance must improve, has become negligible.
All right. Some progress on the actual science. I am delighted to be able to tell you that the amount of science that the Methuselah Foundation has been funding has been rising rather rapidly over the past year. We have been successful in bringing some philanthropic funding in, which I will be talking about in maybe ten minutes’ time. I will talk about a couple of the areas of SENS that we are funding at the moment. The first one is lysosomal enhancement. That is one of the more important of the seven major categories of damage that I have been talking about for the past several years. The approach to fixing this that I favor, as many of you will know, is to identify microbes in the soil or in other places, which have unusual enzymes that can break down the particular things that accumulate in our bodies. That’s what I am going to talk about for a few moments.
There are two major age-related diseases which are the targets of this. Atherosclerosis, which is caused by the accumulation of oxidized derivatives of cholesterol in the arteries. And neurodegeneration, which is caused by the accumulation of various types of protein, usually inside the neuron. This is what Alzheimer’s disease looks like down the microscope. Not very pretty. The idea here is that there is a natural process in the body, a side effect of metabolism, whereby young people are turned into old people, and eventually into dead people. And then there is a completely different process, not encoded in the human body at all, which turns dead people into decomposed people. And that is encoded in the environment, in microbes in graveyards, and so on. So the idea is to identify that genetic process, and to do some standard molecular biology whereby we can manipulate our own cells, so that we can slow down the initial process.
So, results. Well, here are some initial results from the work we are funding at Arizona State University at Tempe, outside Phoenix. We found a couple of strains that could break down this rather important molecule, 7-ketocholesterol. 7KC is probably the most toxic and the most abundant of the indigestible variants of cholesterol that seem to be ultimately responsible for atherosclerosis. And we found a couple of strains that are very good indeed with this. They can break down this stuff really fast, in only ten days. This is really good because it means even if when we put these enzymes into the body they are attenuated in their efficacy by an enormous factor, because let’s say they’re not at the right pH or whatever, even if they are 1000 times less good, then this is going to be fine. Because these things are accumulating in the arteries really, really slowly. All we have to do is outpace the rate of accumulation. So, that’s brilliant.
This work is sufficiently solid now that it is being presented in public. This was a poster that the group from Arizona recently presented at a conference in San Antonio. And the first paper has just been submitted for publication. The students up here are the main people involved and the Pis have worked for many years in Bioremediation, the use of bacteria to decontaminate the environment, and they never dreamed that they would ever do anything medical in their entire lives, and they’re loving it. So, that’s the situation with lysosomal enhancement. I’m very happy with it.
Another part of the SENS program, with which I think a lot of people here are familiar, is the idea of putting the mitochondrial DNA into the nucleus, thereby making mutations in the mitochondrial DNA harmless, because the proteins that the mitochondrial DNA encodes will be provided from the outside, so to speak. And I think this is a good example of accelerating change in action. This was not my idea. It was first conceived in the mid-’80s, not for gerontological purposes, actually. It was first attempted in 1986 and only took two more years before the group in Australia that was trying this got it to work unambiguously in yeast. That was just with one gene of the 13 genes we need it to work on, but still pretty good. A few years after that people started to wise up to the idea that it might be useful for biomedical purposes to put this DNA into the nucleus. In 1993, another Australian suggested that it might combat aging somewhat.
But, these early successes encountered a few problems. People did not achieve the specific aims that they had described in their grant applications. They went back and requested more money, and were turned down, and they just gave up. So nobody had funding for allotopic expression work around the time that I started thinking about this, and gave a talk in San Diego and started being, shall we say, un-mealy mouthed about how pathetic it was that no one was really working on this. A very important mitochondriologist named Mike King was in the audience. It was the first time I’d met him. He got interested in this and a few months later he started to collaborate with someone who didn’t really work on mitochondria [but had worked on chlorophyte algae which exhibited the natural migration of mitochondrial genes into the nucleus.] They successfully cloned the genes from the nucleus and got some good hints as to how we as humans with biotechnology could transfer our human genes from the mitochondrial DNA into the nucleus. I suggested a particular refinement of the allotopic expression concept, which I haven’t got time to explain at the moment.
Around the same time a group based in Washington, D.C.- well, “group” is a bit of a euphemism, it was really just one guy who had been allowed some space in a lab of someone he knew- got some real success in a type of cell that comes from a hamster. A mammalian example. Nothing happened for the next five years. Basically, it was just ignored. But wheels were turning in people’s minds. The idea that this might just not be quite as impossible as people had begun to believe previously was beginning to emerge again. And it emerged in spades in the past few years. I was able, as one of my earliest actions when I started rejuvenation research to publish the result that previously they had not been able to publish. A group from Madison was able to get funding from a very respectable source, The Ellison Foundation, to work on this in mice. A group in Paris has worked successfully on another complementary approach to making allotopic expression work. A group in Spain is using the approach that I suggested six years previously. And finally, we are also funding one group in Cambridge in England to work on this project. We will almost certainly be funding one or more of these groups who are currently working on it, at an entry level scale.
Related articles: Popular Arguments For and Against Life Extension. George Dvorsky discussed mainstream memes found in association with the issue of radical life extension.