Though some areas of SENS, such as stem cells and amyloid immunotherapy, are sufficiently mainstream not to need funding, most are still relative backwaters that rely on the Methuselah Foundation to progress. As a result of the great generosity of donors, the non-profit organization trebled the diversity of its research in 2008. At the BIL unconference in February, Chief Science Officer Aubrey de Grey gave an overview of the research projects that the organization is now funding, their significance to SENS, and their potential to lead to accelerated progress towards the defeat of aging in 2009 and beyond.
The following transcript of Aubrey de Grey’s BIL unconference presentation “SENS Progress Worldwide” has not been approved by the speaker. Video is also available.
SENS Progress Worldwide
For anyone who has seen me talk before, you have seen this table. This is a one-slide summary of how I think we are going to fix aging. Essentially about ten years ago I realized that the weak links in aging, the types of molecular and cellular damage that accumulate late in life and eventually cause age-related diseases, decrepitude and so on, can all be split up into these seven major categories. This is really good news because for each of these categories we know more or less what to do about them.
I do not mean to slow down the progression of these things and the accumulation of these types of damage. I actually mean to get rid of the damage, after it has happened. I have listed them there, and if anyone would like to know more about that, obviously you can read my publications, especially a book I had out about a year ago called Ending Aging. It has an entire chapter dedicated to each of these things, which was mainly written by my unbelievable research assistant Michael Rae, a fantastic writer for a general audience. There is a paperback edition to the book that came out four months ago, and that is my first piece of good news for you.
The paperback edition was a year later than the original. So much had happened in the meantime that we had to write an entire new chapter to cover all of the wonderful progress that had been made in these various areas. That is all definitely good news. The problems have not got harder as time has gone on over the past year or two.
However, the Methuselah Foundation is still pitifully small. Out of these seven things, the only two that we were actually putting serious money into were these two here: mitochondrial mutations, a big problem in aging that we think we can fix by essentially making the mitochondrial DNA superfluous, and the accumulation of garbage inside cells, which is the main focus of the group that we support in Arizona, and also the group that we support in Houston, Texas.
We have been funding both of these things for at least a couple of years. You see here that in red are the areas that have been funded by the Methuselah Foundation since 2006. There are none of those. That is because we had not been able to expand the diversity of our research for the previous couple of years. Now I will show you how it all changed.
This man, Peter Thiel, who you probably recognize, first of all gave us a fair chunk of change towards the end of 2006. In the subsequent three years he has committed to giving us a 50% supplement to any donations that we get from anyone else for research, so a one-for-two challenge pledge. The first year of our pledge, which was the year 2007, we did not get the maximum amount he committed to giving us. (This was a million dollars maximum per year, if we got two million.) We did not get that much—only about a third of that much, and yet he gave us the whole million anyway. What a complete stunner!
I always tell everyone that everybody can do something to contribute to the mission: If you’re a journalist, you can get me on the television. If you’re a politician, you can start changing policy. If you’re anyone at all, you can engage in advocacy… but if you’re a billionaire, there’s something very specific you can do, and this man’s done it.
Anyway, this is really the main reason why things have changed somewhat in the past year. The good news is that in this year, since the beginning of 2008, we started funding quite a lot more. We have been able to more than double the diversity of our research support in universities around the world. This bottom one, which is the approach that I have proposed for really, really curing cancer is something that has lots of components to it, but we have started funding a couple of them.
These are the four things that are really new projects in the foundation. These are things that I really wanted to spend a few minutes summarizing, especially for those of you who are bored to death about all the other stuff that you have heard me talk about a dozen times before.
A fantastic, originally Serbian immunologist called Janko Nikolich-Zubich, who is a prominent gerontologist and works in Tucson at the University of Arizona, has become very interested in the possibility of being more ambitious about repairing and rejuvenating the immune system than anyone has previously been. There are two major things that go wrong with the immune system during aging and they fall into two of seven categories that I always talk about. People have been exploring these things in isolation in a somewhat halfhearted sort of way for quite some time, but no one has had the balls to do them together.
I have managed to persuade Janko to do this. He is basically applying a combination therapy to mice whose immune systems are going downhill because of aging and seeing whether the immune systems can be really rejuvenated so that the mice are better at resisting infection, getting back to where they were in early adulthood. It is a reasonably long project, as is more or less any project involving the aging of mice, but it is already underway. It is being funded by the Methuselah Foundation and we are extremely happy about it.
Jan Vijg is a professor at Albert Einstein in New York and another very prominent gerontologist. He is another strong supporter of the general principle that I have been putting forward for the past two years. His main theme is the accumulation of nuclear mutations. (This is not mutations in our mitochondria, but mutations in our chromosomes.) He has for some time taken the view that the accumulation of non-specific mutations, mutations that randomly disable some aspect of the cell’s function, may actually be a major driving force in the rate of aging. I think he’s wrong. If I thought he was right, then I would be much more pessimistic about our ability to do much about aging anytime soon, because let’s face it, it’s pretty tricky to mend mutations in the nucleus. We are probably going to need molecular nanotechnology before we can do that.
I think we are lucky that actually the only thing that really matters as a consequence of nuclear mutations is cancer. As many of you who are familiar with my work will remember, I have a specific approach to dealing with cancer. My take is, if we can really get that working, then all the other things that the accumulation of nuclear mutations might cause will not actually matter for a long time—several times a currently normal lifespan. We can afford not to worry about that for a little while.
Jan, as I said, disagreed with me on this. He claims the mutations may matter in a normal lifespan, but he is such a damn good scientist and such a nice guy that he is doing an experiment that he did not want to do, and he’s doing it for me. Basically, he is having a look at the brain to see whether the brain accumulates what we like to call epimutations. These are not changes to the DNA sequence, but changes to the decorations of that sequence: things like methylation of histones, methylation of CpG dinucleotides. These are things that cause changes to which proteins are actually expressed from the genome, as opposed to which proteins could be expressed.
Jan found some years ago that in the brain actual bona fide mutations do not accumulate at all in mice during the whole of adulthood. They accumulate during growth, but after it the mouse gets to full size and nothing happens. Of course, if nothing is happening, then it cannot matter in aging. For this reason, it is very important to determine whether the same is true for epimutations. I think it probably will be, and he is having a go. If he finds that there is some change, then of course we have to find out whether there is enough change to actually matter. That is a whole other set of experiments.
That, again, is underway now. I should say that for both these projects, the people actually doing the work are not the professors, but the people working for the professors. In both cases we have an absolutely splendid person that each of these people have brought in. I am really happy that two accomplished and talented post-doctoral fellows are actually doing the experimental legwork here. I am delighted at how these projects have got going over the past few months since we started funding them. It really is happening.
Now, demography is not usually listed in my seven strands of what we need to deal with in order to defeat aging. However, as all of you know who have tried to talk to people who are not terribly persuaded that this would be a good idea, it is really important to think about the social consequences of defeating aging so as to be able to call the bluff of the idiots who actually say that aging is a good thing. Of course the biggest reservation that people normally have when you talk about defeating aging is “Oh dear, there will be lots of people, won’t there? That will be terrible.”
I have lots of fairly sarcastic answers to this, of course. However, it would be nice to actually have some data. What we have decided to do is create a really authoritative study, along with some software that can be used as the substrate for creating other studies, that will allow us to see what the demographic consequences would be of developing therapies that generally knocked aging on its head. This would be on the basis of various other permutations and assumptions, like how rapidly technology accommodates increasing population, how rapidly the birthrate declines, how rapidly these therapies spread around the world when they actually arrive, all those things.
The Gavrilovs, Natalia and Leonid, are professors in the University of Chicago. They are, again, very good supporters of this whole mission. They are some of the most pro-anti-aging, so to speak, demographers in the world, in marked contrast to other demographers. They are doing this work for us, and furthermore, it is not very expensive. It does not involve test tubes. I put this down on the bottom rather cheekily, because we have not strictly speaking signed the contract yet. We will probably do so next week.
Lenhard Rudolph is a professor in Ulm, a city in Germany. He is one of the experts in the manipulation of telomerase in mice, the enzyme that maintains the length of chromosomes. He has done some good work in this area over the years. In particular, he is the world’s leading specialist on the manipulation of mice with respect to the blood. Now, the blood is a tissue which is going to suffer if we do what I think we need to do in order to really defeat cancer. It is going to have side effects on the ability of stem cells in the blood to actually continue to work indefinitely.
The way that I propose we are going to get around that is by periodic replenishment of the bone marrow through the stem cells to the blood, but we need to determine that this is actually going to work. This is the world’s best person to do this experiment, and he is going to do it. I am pretty happy that all these things are happening, and it is mainly because of Peter Thiel. I bow down to his generosity.
I bet a lot of you know undergraduates, so you can talk about this to them. This is an initiative, the Methuselah Foundation Undergraduate Research Initiative, which was put together pretty much single-handedly by another of the mindblowing people that I have had the great good fortune to be able to attract into my team. This is a guy named Kelsey Moody, who is an undergraduate at Plattsburgh University in Upstate New York. He has basically discovered that if you are an undergraduate, you can do lab work and it will be really well subsidized, you will get credit, and all that sort of stuff. He ended up putting together a very well organized structure for us to attract people to do such projects, and also he is running the whole thing in his spare time.
This is a really new venture that is moving forward fast. Essentially, this is a description of what’s going on. We are doing things if you are an undergraduate outside the U.S. that is related to this. Within universities in the U.S., independent research can be done at no cost to the students, so long as they find a lab to do it in and a faculty mentor. Using this mechanism, this organization that Kelsey Moody has put together utilizes undergraduate research to perform research that benefits the SENS agenda.
Of course, undergraduates are fantastically cheap. They are almost as cheap as graduate students. We have a scholarship program, and grants applied to cover the basic costs of the lab work. Kelsey Moody is orchestrating the whole thing, but visit mfuri.org and you can go from there. I am really excited about this initiative. It is going to make a big difference.
There is some bad news, of course. There are still masses that we are not able to fund yet because we are still far too small. I should point out that all the red ones above are not actually funded. They are really only partly funded. In each of these categories there are many types of things that go wrong. In each case we are just analyzing one example of that category. In other words, there is lots and lots that we want to do in each of those categories that is not within our current budget. However, it’s better than nothing.
There is another piece of very bad news. Nobody has got any money to give us anymore. That is not completely true, but it is not looking very good. I have spent a lot of my time over the past few months talking to people who have been wringing their hands a great deal in response to the situation at the moment. This obviously has hit a lot of charities very hard. I think it is going to be a challenging year for pretty much every non-profit in the world.
This is a shame, but we are working on it. We have a few leads that may lead to a substantial increase in funding during this year. Of course, that is what I spend my time rushing around the world trying to make happen, so wish me luck. I’ll stop there.