Aubrey de Grey is the Chair and Chief Science Officer of the Methuselah Foundation, a non-profit organization dedicated to combating the aging process. In this talk presented at the February Silicon Valley Transhumanist Meetup, he outlined the several most notable developments in funding and research taking place at the Methuselah Foundation in late 2007 and early 2008.

The following transcript of Aubrey de Grey’s Silicon Valley Transhumanist meetup talk has been corrected and approved by the speaker. Video is also available.

Methuselah Foundation: Early 2008 Developments

Yesterday I was in Philadelphia, and often I give talks of course to audiences that do not know my work at all, so there I could give a talk at ten minutes’ notice, because I could just give a standard talk. Of course, it would be a little bit insulting to you, most of whom I actually recognize, to just tell you stuff you already know. I thought I would try not to do that. The result is that this will probably be rather shambolic, but anyway, here I am.

What shall I talk about? Perhaps it would be useful, since the things that I can be most confident you don’t know about are the most recent things, to talk about the stuff that has been happening recently in the Methuselah Foundation and related work. I thought I would start with telling you how things went toward the end of last year, because it was really rather good news. A number of the things I am going to tell you now have not actually been publicized in press releases and stuff like that yet, but I’m not really giving away any secrets. It is all very new news, anyway.

FUNDING

The first thing that happened was that somewhat by accident, we got into a situation that very rapidly accelerated the influx of relatively small donations to the Methuselah Foundation. As many of you will probably know, we have an ongoing challenge pledge from Peter Thiel, the co-founder of PayPal, who gives us fifty cents for every dollar we get from anywhere else. That has been going okay, but it could always go better. One of our existing medium-sized donors, a guy from Texas called Mike Cooper, said he would like to give us another $25,000 in December and that he would like to do it in a manner that leveraged it more. So he said he would like to use it as a booster for the challenge pledge that already exists, turning it from a one-for-two pledge into something better. We turned it into a two-for-one pledge, basically. After this pledge is in place, anyone who comes along and gives us a dollar, we get a total of three dollars.

Well, it worked miracles. We exhausted his 25k in a week or thereabouts, and someone else came along who had given us a few thousand dollars some time ago and said he would like to do the same thing. He gave us another 25k, and we were also able to use a donation that we had been pledged last summer from Ryan Scott, who you may know. Ryan Scott is a dot com multi-millionaire who is very interested in these sorts of activities in general, and life extension in particular. He pledged us $100,000, and we used that in the same way. We are going to try and keep this sort of thing going. It seems to be a very good way to encourage donations.

The biggest things that happened toward the end of last year, a guy called Bill Liao, who is one of the founders of a European competitor to linkedin, a company called Xing, he decided to give us more than a half a million dollars—spread over six years, but that’s okay. Furthermore, it’s not in dollars. It’s in Swiss francs, so it might actually be worth something. The best piece of news of all, Peter Thiel decided to do a bit more last Christmas—he gave us a rather nice Christmas present. The current deal is that during each calendar year, he will give us a maximum of a million dollars, and so we are out to get two million dollars in that year in order to get the whole million. We only actually got about two-thirds of a million dollars, so we only got about a third of what we need to get that whole million in. But he said, “*** it, have the whole million anyway.” Something along those lines. He was sufficiently pleased with how we had been getting on, and reckoned we had done well enough.

The long and short of it is we had a rather good December. The reason I thought I would start by telling you all this is that now that we have all this money in, we can spend it on research—on getting more of the SENS plan actually started. Of course, that is my job as Chief Science Officer of the foundation, to actually make sure that the right professors are in a position to do the right work as soon as possible. Of course, to a certain extent, I have been able to do the first stages of that before the money had actually materialized. I spent most of last year, in one way or another, creating small heads of steam around the world, getting various professors to know that there might be some money to do particular things that they might be interested in doing, but not being able to tell them when it would be. There is just so far you can go with that without really pissing people off, of course. The money, having actually materialized, there is an enormous amount of work to do to sort out what is going to be done, the intellectual property assignments, things like that.

So, it has been a lot of work. But the upshot is that we will be able to initiate at least three, and perhaps even more, projects this year, over and above the two big projects that we have been doing over the past couple of years—namely, the identification of bacterial genes that can break down things that we can’t, and the relocation of mitochondrial DNA into the nucleus. Both of those projects are obviously continuing and will be growing, in terms of manpower, during this year. Those of you who have been following this work for some time will probably know about that because I talk about it quite a bit in talks. I thought I would talk a little bit, somewhat shambolicly as I said, about the things that we are currently planning to do some more of.

RESEARCH

How many people in the room have read my book already? That’s good, because I am going to give a bit of background to each of the things I will be talking about. Another thing we are lucky to do, which is part of the complex anti-cancer strategy has to do with stem cells in the blood. If we were to develop a drug that could go in and delete the genes for telomerase so that telomerase could not be turned on, and it only went to the cancer cells that were already cancerous, that would be great in that cells that need to have a bit of telomerase turned on, which includes the stem cells for all of our continuously renewing tissues like the blood, the gut, the skin, and the lung, they would be okay. Unfortunately, a very common tactic that cancers use to resist and escape certain drugs of all sorts is they figure out ways to destroy the drug or exclude it from being taken up in the first place. A minority of the cancer just won’t see the drug, and that is quite enough.

WILT

I have always felt that this approach of deleting telomerase will require us to be preemptive, and go and hit all of our cells, not just the cancer cells. That means we are going to have a problem. If we did that and did not do anything else, we would not die of cancer, but that is because we would not have time to die of cancer, because we would have died of not having any blood sometime previously. The only reason that this whole approach ever seemed reasonable is because of the possibility of stem cell therapy—the ability to put cells back into these various tissues, stem cells, so that the tissue can remain immortal and continue to produce differentiated cells of various sorts, even though each individual stem cell in the tissue is not immortal.

There are only a few tissues that we have to worry about: blood, skin, gut, lung. Blood, ostensibly, is the easiest one here, because of course replacement of stem cells in the blood is something that we have been doing medically for rather a long time. That’s what a bone marrow transplant is. There are things that make bone marrow transplants not as effective as we would like. Again, there have been some recent advances that have really helped us to become more optimistic that we can do this. One thing that was reported out of Stanford just a couple of months ago, a group found a way to remove the stem cells from bone marrow in a way that did not involve radiation. This is really important, because radiation is bad for stem cells, but it is bad for other cells as well. It is not something you want to do if you can possibly avoid it. This splendid paper reported a way of depleting the stem cells just using antibodies to a protein being expressed on those cells. This is a much gentler approach, much less likely to have major side effects than radiation. It is a major breakthrough for a whole bunch of reasons.

The process of replacing these stem cells in the bone marrow has to start somewhere. If we are taking a mouse, let alone a human, and we want to make all of the stem cells in the bone marrow telomerase knock-outs, then we can get some stem cells out and delete the telomerase genes, then check that we have made the right modifications, but in order to get the stem cells back in, we have to do more than just inject them. We have to ensure that the stem cells go into the bone marrow and actually take—they engraft. Bone marrow transplants are okay for people who are already sick—in other words, whose bone marrow stem cells are already dying, for whatever reason. But if the bone marrow cells think they are fine, it’s just that they might be at risk of becoming cancerous some decades in the future, it turns out it doesn’t work so well. Stem cells that are happy tend to like to stay where they are, in what is called the stem cell niche. They just do not get out of the way and allow other stem cells that we may have injected to replace them.

This trick of depleting the stem cells using this antibody is going to make a big difference to the ability to replace stem cells. Partly because of this new advance, and partly because of a couple other advances in the telomerase field, once thing I have decided that we need to fund is seriously careful studies on the ability of stem cells that do not express telomerase to go in and behave just as if they did have a telomerase gene. You might think, why shouldn’t they just behave the same as normal? Telomerase is only being expressed at this low level in stem cells anyway. Suffice it to say, there is a lot of literature out there that has been purporting to cast doubt on that assumption. There may be other roles that telomerase has over and above the lengthening of telomeres.

I personally think that a lot of this work has been somewhat over-interpreted, but it remains to be seen. This is partly a case of just seeing whether this particular component of the anti-cancer strategy that I have called WILT is going to work at all. Taking it forward in mice, we will be determining whether the stem cells need to be introduced into the mice when they are young—in other words, when the bone marrow has not become aged in some other way. To the extent that that might not work, we will need to determine what aspects of the stem cell environment are somehow inadequate. The good news is that there is one particular laboratory in Southern Germany that has been working in this general space for a few years. I have good relations with the professor and he is very interested in taking a slightly different tack in the direction I have just been describing to you so as to find these things out.

CD8

Another area of SENS that is completely separate from cancer is the elimination of cells that won’t die. Of course cancer is a problem of having too many cells because the cells are dividing like crazy. They are also dying like crazy, but they are dividing even more crazily. That’s what cancer is. There are other problems that are caused by cells that are actually not dividing, but they are not dying either, and they are accumulating slowly as a result. They get in the way and cause various problems just by being there.

Probably the most serious example of this is the immune system. In the immune system we have a wide range of different types of white blood cells that have different functions in protecting us from infections. They have a large number of different things to do. There is one particular type of white blood cell called a cytotoxic T lymphocyte—CD8 is the name of the protein that these cells express on the surface—that is the main problem in respect to this accumulation of cells that I mentioned.

Here is what happens: Some viruses that we get are what are called “persistent,” which means that we get this infection and the immune system brings it under control, there are no symptoms, but the immune system does not succeed in completely eliminating the virus from the body. The virus hangs out, latently, in one or two places. There is a particular family of viruses called the herpes viruses, which are particularly bad at this. Within the family of herpes viruses, there is one virus called cytomegalovirus, which used to be considered completely harmless and uninteresting from a medical point of view.

Cytomegalovirus, clinically, does not present any obvious symptoms except in people who have got advanced AIDS or other really severe problems with their immune system. It seems to be the number one reason why you have these CD8 cells accumulating in old age in most people. Most people are infected with CMV from an early age. The way it seems to work is that these CD8 cells, which are specific to CMV and are involved in controlling it, divide. They essentially get rid of a lot of the virus but not all of it, and every time that the virus tries to have another go, it gets beaten back, but it gets beaten back by another round of division of the same family of cells.

What seems to happen is a sort of somewhat variant form of what is called replicative senescence in virto—the concept that so many of you heard about from Len Hayflick fifty years ago, whereby cells end up, due to telomere shortening, getting into a state where they cannot divide anymore. Now, in the immune system, there is a lot of cell division that goes on, and for that reason, telomerase is turned on when it is needed. But, probably as a secondary anti-cancer strategy, cells in the immune system—especially CD8 cells—do not like to do that indefinitely. They get into a state where the sort of stimulus that would normally make them proliferate and turn on telomerase, only makes them proliferate and not to turn on telomerase very much. It leads to an interesting state where they will not divide at all. It will neither divide nor turn on telomerase.

There are various ways we might deal with this problem. One is to turn on telomerase for them—stimulate their telomerase. Actually, that is a method that is being explored by a very eminent professor in this area, Rita Effros at UCLA. I am a little bit worried about that, because it seems to me that this is somehow subverting what I think is likely to be an anti-cancer response. This may have side effects in terms of lymphoma, really rather rapidly. I would rather be in favor of simply getting rid of these cells. What is wrong with these cells anyway? They are not dividing, but other cells can divide instead, and carry on keeping our immune system happy. The problem is that as you get more and more of these cells that are not dividing, there is the inhibition of the proliferation of other white blood cells. There is a system in the body that keeps the total number of white blood cells of various sorts reasonably constant. There is a whole bunch of accumulating useless ones—that leaves less room for useful ones.

There is now a pretty good consensus that this plays an enormous role in the progressive decline of function of the immune system during old age, so we would really like to fix it. The very best solution would be to actually eliminate the virus—to find some way to do what the immune system is not succeeding in doing and get rid of this virus. But the immune system is very, very clever and we are not that clever yet. The cytomegalovirus in particular is also very clever. It is a very big virus with a couple hundred genes, and we really do not know half of all the tricks it uses to hang out and not be eliminated. We may find ways to eliminate it, but it is not looking like that is an approach whose time has come. The second best is to get rid of these cells that are getting in the way. There has been some good news in that area in the past year as well.

Essentially, these cells have been progressively better characterized. At first it was only possible to identify them by virtue of the fact that they had a bunch of things on their surface that a lot of other useful cells also have, but there was one gene that they did not have on their surface that the useful cells do have. In other words, it was a negative characterization of these cells. It turns out that this is a really tricky thing to use as a target—as a way of actually identifying them clinically. What you really want are things that are expressing things that useful cells like them are not expressing—and that has now been found. There are now a combination of two particular genes, one or other of which is sometimes expressed by useful cells, but both of which are not. That is going to be rather handy in developing therapies to fix this problem.

There are also improved techniques to do something called suicide gene therapy, which is essentially a system whereby you introduce a virus into the body that will go into a lot of different types of cells, and this virus encodes a gene that is really bad for cells, and kills cells. You would think that would be a bad thing to do to people, and at this point it is, but it is a technique that has actually been used in model organisms quite a lot, because what you can do is arrange that the protein that is toxic is only expressed if the virus that you have injected goes in cells that are expressing some other particular protein. Essentially you put what is called the promoter region of some other gene upstream of your toxin and that means that the toxin only gets expressed when the other gene is also being expressed. There are of course elaborations of this sort of system that can be used so that it is only turned on when there is DDP expressed, or something like that. The idea is that you can actually be pretty indiscriminate about where these viruses that are suicide packages will go, because they will do no harm in places where you do not want them to do harm. They will only blow up and kill cells that you actually want to get rid of.

THYMUS

This is conceptually a simple idea. As tends to be the way in biology, in practice it is quite messy. But, again, progress is being made in this area. The upshot is that there is a good chance that we are going to be able to fund a project starting this year that will get a good deal further towards the goal in mice of eliminating these clonal expansions of what are called anergic—essentially broken—CD8 cells. The hope certainly is that this will play a large role in rejuvenating the immune system. There is one other thing that we want to do that is also required for rejuvenating the immune system, and that is to restore the size of a very important organ in the immune system called the thymus, which is—for whatever reason—something that shrinks throughout life and gets, even by the sort of age I am, down to 10 or 15% the size that it was in early life. It is believed that this has also a rather large role to play in the increasing dysfunction of the immune system. We want to regrow the thymus as well.

AMYLOID

There are a few labs that are looking at that. There is one lab in particular that is looking at that, and is also looking at the problem of getting rid of the anergic cells. That is the lab that I am currently most interested in funding to take this whole thing forward. That is three things that we are doing. Another one is amyloid. This is the stuff in the brain that accumulates in Alzheimer’s disease, and probably plays some role in exacerbating the progression of Alzheimer’s disease. There is still a good deal of controversy as to whether that is actually true—whether it is part of the damage, or whether it is actually harmless. For a bunch of reasons, we can say that we ought to get rid of it. If it is protective, then it is protective against something else that we are also fixing independently in the SENS plan.

Amyloid in the brain in Alzheimer’s disease is the topic of some of the best news of the year in biomedical technology. This is years that has not really got out yet because it is a bit commercially sensitive, but I will tell you anyway. About nine years ago, a company in south San Francisco called Elan Pharmaceuticals discovered and published in Nature that if you make a mouse so that it gets Alzheimer’s, which mice do not normally do, you can then get rid of the amyloid that accumulates in the mouse brain by vaccination—by stimulating the immune system so that it gobbles up the amyloid. This was a bit of a surprised, because amyloid is a protein that the body makes naturally, so you would think that like any protein that we make naturally, the body would be tolerant to it. Of course, that is the problem. The body is too tolerant to it, but there are ways to manipulate the immune system to be slightly less tolerant to one thing than it otherwise might be. That is essentially what was done. It was a vaccination to make the immune system think this was a bit foreign, and to gobble the stuff up.

There was preliminary data showing that this did actually cause an improvement in the cognitive function of the mice. It was obviously a pretty high profile paper, but more than that, the people who were working on it knew that this was important to move to clinical trials as soon as possible. It is said that the FDA did not cut any corners, but all I know is it went from mice to Phase I clinical trials and Phase II clinical trials faster than I have ever heard anything go. And a good thing too, because obviously Alzheimer’s is quite bad for quite a lot of people.

The trials started in 2001. Unfortunately, it was a failure. It was a failure in what some people might think is the worst possible way. Namely, it had bad side effects. I think the worst possible failure is something that you spent ten years doing and just does not have any effects either way. This, at least, the side effects were found within one year. The side effects only affected about 5% of the patients, but that was quite enough, because the side effects were quite severe—neuronal inflammation. One could argue that they moved to clinical trials too fast. Actually, it could have been worse. They had not thought through the likely consequences of the particular manipulation to the immune system that they were doing—active vaccination. This is essentially putting the stuff that you want to be gobbled up into the brain, and letting the patient develop their own antibodies and mechanism for getting rid of the stuff.

There is an alternative type of vaccination called passive vaccination, which involves doing the actual creation of antibodies, not in the patient but in the way that we normally create antibodies in scientific work—in rabbits. Then injecting into the brain not the amyloid substance that is supposed to stimulate the immune system, but rather, putting just the antibodies in. That sometimes can be just as effective as a stimulus to the immune system, but it stimulates slightly different bits of the immune system. This is where I am saying that in some sense the rush to clinical trials may have been a bit too much of a rush, because everything I just told you in the past couple minutes was already known—that the bits of the immune system that are activated by the active approach to vaccination are known to have a risk of causing inflammation, whereas the bits that are stimulated by the passive vaccination were pretty much known not to have this problem.

However, that is all water under the bridge. Because they figured out very quickly that they really ought to have used passive vaccination, and because more or less everyone agreed with them, they managed to start another trial pretty quickly using the new protocol of passive vaccination. At the same time, incidentally, a whole bunch of other groups have been looking at other variants, using active vaccination but with tricks that stop the inflammation, things like that. None of those have gotten far enough to be reporting yet.

Here is what has happened with the second trial from Elan. They have partnered with one of the biggest pharma companies in the world—Wyeth, for what it is worth. They went through a Phase II clinical trial. Clinical trials are, like any experiment, you have to do them in such a way as not to be biased by the results. Not to have some sort of feedback where you might influence the experiment by what you expect. That is why most clinical trials are done in a manner that is called double-blinded, where the investigators do not know who is getting the drug and who is getting the placebo. Of course the patients do not know that either. In clinical trials, sometimes, you get a drug that is so unequivocally good that enough information is coming back just anecdotally that trials get what are called “prematurely unblended.” The data are analyzed at an earlier stage in the process than what was originally intended. If it is indeed confirmed that everything is completely wonderful, the trials gets abandoned and the drug gets approved and there you go.

I cannot tell you that that’s happened with respect to this drug. That did not happen. But it is only one step below that. What has happened is this. Last year they had what is called an interim peek. They had a bit of a look at what was going on, and they started Phase III at once. That is almost as rare as abandoning a trial and approving a drug. It is fantastically good news. Because it was an interim peak and the Phase II trial was still going on, they have to finish it properly. They had not unblinded it or anything. That means they cannot go public about this. One only knows about this if one reads the press releases very carefully and goes to the right conferences and talks to the right people. The long and short of it is that a lot of people are not wanting to count their chickens before they are hatched. Rightly so, because clinical trials go bad late in the process rather often. But, it’s looking good.

Why am I telling you this? I said I was going to be telling you about the sort of things that the Methuselah Foundation are trying to fund this year. The thing is that amyloid is a more general concept than Alzheimer’s. There are other tissues in which amyloid accumulates. In particular, there are other tissues in which amyloid accumulates slowly and progressively during aging. There is one important tissue, which is the pancreas. It turns out there is a different type of amyloid that is primarily composed of a different type of protein than the main component of Alzheimer’s amyloid, which accumulates in the pancreas and which has been shown quite definitively to contribute to the progression of type II diabetes because it kills islet cells. You probably know type II diabetes is a process in which initially the problem is not in the pancreas at all, but elsewhere in the body, with insulin being unable to do its job as well as it should. This is the concept of insulin resistance. The pancreas initially compensates by making more insulin, and that is why if you have got high insulin, you might have good glucose tolerance but you actually have reason to be worried, whereas what you want is to be someone like me who has perfect glucose tolerance just by having virtually no insulin at all.

The second phase of type II diabetes is where it starts to be like type I, because the pancreas maxes out, and starts getting to a point where the islet cells die of stress, so to speak. You actually have a depletion later on in type II diabetes of the ability to make enough insulin, and that is why type II diabetes accelerates. This amyloid that I have just mentioned seems to play a part in that last process. People just have not looked at the corresponding approach. They have not looked at an immunological approach to get rid of this what is called islet amyloid. They probably have not done so because nobody was quite sure yet whether it was going to work in the brain with Alzheimer’s amyloid in humans. There were other approaches that were perhaps going more promisingly against type II diabetes, for example. My feeling is at this point that probably this work is going to happen fairly soon, but that now is the time when enthusiastic professors can be found who will be interested in pushing this work forward faster than they otherwise do at this point.

There is another type of amyloid which is even more neglected and poorly understood, which derives from a protein called transferrin. Transferrin is a protein involved in thyroid hormone transport. It accumulates as amyloid in the heart, and in other places as well, but the heart is where it seems to matter particularly. It seems to be really bad for really old people. Apparently there is a lot of what is called senile systemic amyloidosis in centenarians. The heart is the tissue that is most affected in terms of loss of function. In supercentenarians, which is people who have reached the age of 110, it seems to be fantastically common. The group based in Los Angeles called the Supercentenarian Research Foundation, who are working to study what goes wrong in supercentenarians and how they manage to live as long as they do, have got to the point of being able to organize and perform autopsies on a few of the very few people who actually live that long, and more than half of those people appear to have died of senile systemic amyloidosis.

This is definitely not something that we can ignore if we want to seriously do damage to aging. Therefore, again, it is critical that we start to develop an immuno-therapeutic approach to transferrin amyloidosis with the same ideas in mind. There are some things being looked at by the one or two labs that look at this stuff, but they are a good deal more likely to have side effects. I am very keen to promote work that follows the protocols that seem to be going so far in Alzheimer’s amyloid. That is another thing that I hope we will be able to fund this year. I have a few other ideas of things we might fund that are slightly further down my list if I get another million dollars tomorrow, but for the moment, I think I’ll stop there. Thank you very much

--------------------

James Clement is the Organizer of the Silicon Valley Transhumanist Meetup.   Tremendous thanks is given to Drew Reynolds, for video recording Aubrey de Grey's speech at the Meetup, as well as transcribing same.  The original transcript and video was posted on Michael Anissimov's Accelerating Future website. 

In the face of existential risks and the possible misuse of increasingly powerful technologies, the nonprofit Lifeboat Foundation is pursuing a variety of options, including helping to accelerate the development of technologies to defend humanity, and even self-sustaining space colonies for when other prevention strategies fail. To learn more, Betterhumans Deputy Editor Parish Mozdzierz spoke with Lifeboat International Spokesperson Philippe Van Nedervelde.

Betterhumans: How did the formation of the Lifeboat Foundation come about?

Philippe Van Nedervelde: Lifeboat Foundation's founder, Eric Klien, was shaken wide awake by 9/11.  The new reality of what we call (exponentially accelerating) "Asymmetric Destructive Capability" (ADC) fully hit him: ever smaller groups of people can create ever more enormous amounts of damage. And all of this thanks to advances in technology. As a bracelet-wearing cryonicist, he knew of the potentials of nanotechnology (having attended MIT Nanotechnology Group meetings in the late 1980s), and that 9/11 was just a taste of things to come.  Accordingly, the Lifeboat Foundation was incorporated within months of 9/11.

BH: What is the "A-PRIZE," and how does it apply with your mission to prevent existential risks?

PVN: The purpose of the A-PRIZE is to put development of artificial life forms in the open where it should be. Today, many efforts at developing artificial life are not well publicized. The A-PRIZE serves as a clearinghouse for information about the race to "Break the Carbon Barrier." With mega-universities and companies racing to create nonbiological life, now is the time for such a clearinghouse.

The A-PRIZE is awarded to the person or organization responsible for creating an animat/artificial life form with an emphasis on the safety of the researchers, public, and environment or the person or organization who shows that an animat/artificial life form has been created. (The second case is to uncover unpublicized or unsafe projects.)

It applies to our mission as it both encourages the use of safety measures in this ongoing international effort to create nonbiological life and also offers rewards to uncover unsafe efforts.  Unsafe efforts could devastate our biosphere, and without the spotlight of the A-PRIZE to uncover them, humanity could be in danger.

BH: Currently, Lifeboat Foundation has 23 programs devised to fight against various existential risks, including asteroid strikes, bioweapons, nanoweapons, nuclear war, internet attacks, climate change, extinctions and collapse of plant and animal life diversity, unfriendly AI, gamma ray bursts, unexpected solar activity, etc.  Do you ever fear that working on such a large number of diverse risks, that you're losing the ability to focus your efforts on one or two of the larger or more probable dangers? Is there a priority in how your group is addressing these risks?

PVN: Baden Powell's great motto was "Be Prepared." Accordingly, we find that we want to prepare for any eventuality which may do all or most of us in. You cannot know ahead of time which x-risk will prove to be our final undoing. Both individual death as well as species-level extinction can come like a thief in the night, totally out of left of field. We are in the survival business, so our mindset and resolute determination is to leave no stone unturned to budge our survival odds in our favor. We inevitably adopt a rational and eminently pragmatic approach to this.

I have taken the initiative for a new program or project which we now have in preparation called ETO, short for Existential Threat Outlook. The goal of this is to track the evolving statistical probabilities of all the variants of existential risks ("x-risks") that we are looking at. The intention is to update our ETO chart in real-time. This ETO chart will inform and drive our prioritizations in terms of allocation of efforts and resources. We obviously want to allocate efforts according to the statistical probability and temporal proximity of x-risks.

Note that preparations for some x-risks takes more resources than others though, so there is no linear relationship between the imminence of a particular x-risk and the efforts we allocate to its prevention. Also, bear in mind that some programs deal with multiple x-risks in one fell swoop. Some of these are infrastructure type programs and obviously would require great amounts of resources.

Finally, also consider that we pick our battles taking into account what other organizations are doing. Whenever we find that another organization is doing something we agree is very necessary and is doing that faster and better than us, then we naturally do not duplicate those efforts. This is the case for instance with what SIAI is doing regarding the possibility of humanity-unfriendly AI. We also endorse what organizations such as the Foresight Nanotech Institute and the Center for Responsible Nanotechnology are doing.

Unless we find that what such organizations are doing is too little too late, or ill-advised or otherwise unhelpful in our opinion, we will simply support those organizations to the very best of our ability instead of doing what they are already fully focused on. Ideally, we would love there to be at least one active and effective organization totally dedicated to dealing with each individual x-risk. In that case, our role would be blissfully reduced to being an information clearinghouse, a forum... with possibly some coordinating roles. As things stand, we are far from such a situation though.

BH: With which programs have you realized the most success so far to date?

PVN: That depends on what you consider success here. In our view, the programs that have made our current programs list are the ones that have become the most fleshed out and therefore the most successful to date. They are: AsteroidShield, BioShield, InternetShield, NanoShield, SecurityPreserver, and Space Habitats. To date, we have been working on just developing position papers for programs. This is to change shortly though.

BH: Are there some risks you feel are still not getting enough attention, despite your efforts?

PVN: We feel that people generally don't take future risks and x-risks in particular seriously enough. Unfortunately, this is probably a common failing of civilizations. Per Fermi's paradox, this is likely the cause of the fact that-as far as astronomical evidence has enabled us to determine to date-we live in a universe devoid of intelligent life except for our own. So NONE of the future risks / x-risks are getting enough attention, whether they are bioweapons, nanoweapons, or other threats.

BH: Some observers consider the Lifeboat Foundation as not being pro-governments, pro-technology, pro-privacy. Is this the case?

PVN: Not at all. On the contrary. If those observers would give our publications on our website an appropriately close reading, they would understand that we are explicitly, emphatically, enthusiastically in favor of responsibly developed technology, of effective democratic governments and transnational institutions...even of personal privacy to the extent it can be preserved without jeopardizing the security of the rest of us. Again: we are in the survival business. So we are in favor of anything which will demonstrably be of significant help towards achieving this goal. Within reason, we will try anything that helps increase our probability of long-term survival.

At the same time, it stands to reason that, when and if we are justifiably skeptical about the effectiveness of something in this regard (meaning what other people are doing), and unsure as to whether it is part of the problem more than it is part of the solution, we will simply give it the benefit of the doubt until we become more sure...and will not emphasize such in the allocation of our resources at any given time towards the realization of our goals.

BH: What role does Lifeboat have in the upcoming Transvision 2007 conference (from July 23 to July 26 in Chicago)?

PVN: The focus of the Lifeboat Foundation is the theme of this years' Transvision. Accordingly, we will be prominently present in a variety of ways. One major way is by virtue of the presence as speakers of no less than 25 members of Lifeboat Foundation's Scientific Advisory Board. Basically, it will be wall-to-wall Lifeboat Foundation Scientific Advisory Board members! In a way, it will be Lifeboat Foundation's own first big conference.

To be precise, our Scientific Advisory Board members Ed Begley, Jr., José Cordeiro, Mike DeMaio, George Dvorsky, James Gardner, Giorgio Gaviraghi, Jerry Glenn, Aubrey de Grey, Barbara Marx Hubbard, James Hughes, Charlie Kam, Ray Kurzweil, Ed Lantz, Michael LaTorra, Max More, Giulio Prisco, Anders Sandberg, Tihamer "Tee" Toth-Fejel, Philippe Van Nedervelde, Natasha Vita-More, Shannon Vyff, Mark A. Walker, Michael Weiner, Kenji Williams, and Eliezer Yudkowsky will be speaking at Transvision 2007 - Transforming Humanity: Innerspace to Outerspace.

(Editor's note: the Lifeboat Foundation has obtained a promotion code for 40% off the event. To get this promotion code, send an email with the subject "Lifeboat Foundation TV07 promotion code" to tv07@lifeboat.com.) 

BH: Are you planning on filming/recording any of your speakers during the conference?

PVN: Yes, all of them... as long as they sign their release form of course.

BH: When would you plan on having the video/audio available on your website?

PVN: As shortly after the conference as technically possible.

BH: Lifeboat is also involved in the X-PRIZE CUP '07 (from October 26 to 28 at the Holloman Air & Space Expo at Holloman Air Force Base in New Mexico).  What are the details surrounding your EM Launch Competition?

PVN: The EM Launch Competition, as part of our Space Habitats program, will be our first program to be more than a position statement.

We will formally announce in about a week that the EM Launch Competition as described at http://lifeboat.com/ex/em will be featured at the X PRIZE CUP

If you have comments on the proposed Contestant's Contract at http://lifeboat.com/em/em.rtf, please send them to grants@lifeboat.com with the subject "Lifeboat Foundation X Prize Cup 07."

Once this program is formally announced, our next goal will be to make the NanoShield program more than a position statement, and we plan to start working towards fully funding the work of Robert Freitas Jr. and others. We have already raised some funds for his "Thermal Censorship of Ecophagy Study" as we begin to prepare to focus in this area.  You can make donations for this effort at https://lifeboat.com/ex/donations

BH: Any other near-future plans or events?

PVN:  Yes, quite a few. Sergio M.L. Tarrero, Lifeboat's International Director of Audiovisual Communications, is leading a great effort aimed at producing a 100-minute documentary describing x-risks and the various proposals by the Lifeboat Foundation to do something about preventing them completely or, should that fail, at least downgrade their destructive impact to scales of destruction which do not wipe out humanity to the last person. The intention at this moment is to have a worldwide theatrical release of this documentary...and to produce it in at least eight of the most spoken languages of this planet. We also have a series of 30 sec. multilingual TV ads in the works which we hope will similarly contribute to raising worldwide awareness of our foundation's concerns and our proposals regarding what to do about them. So...watch this space!

While the internet's full of false promises to make people taller, only one technique can deliver the goods: limb lengthening. For some, the benefits of a few extra inches are worth the expense and pain of breaking bones and slowly teasing them apart to build height. And for them, the Make Me Taller forums have become a mecca. Betterhumans Editor and limb-lengthening contemplator Simon Smith spoke with the site's anonymous founder, a wealthy Brit known as MMT who has had one procedure in China and plans another soon.

BH: When most people think about leg lengthening, they likely think about a procedure for dwarfism that's often practiced in China on those without the condition. Yet you're relatively tall-taller than 90% of the Chinese population, as I understand it-and live in the UK. How is it that you find yourself such a champion of the procedure?  

MMT: Although the techniques and the technology used in leg lengthening (LL) have been developed over many decades for treating medical conditions and dwarfism, the collapse of Communism meant skilled surgeons in places like China and Russia found themselves with a valuable commodity-the ability to make people taller.

Fortunately, this coincided with a huge increase in cosmetic surgery in the West, and many of those surgeons soon realized that they could offer "height increase" services on a purely cosmetic basis.

The clinic where was I treated in Beijing has done over 1,500 cosmetic leg lengthening procedures, and the clinics in Russia and the former Soviet Union have probably done a similar number. If these doctors and clinics were still tightly regulated under Communist regimes, I'm certain that their services wouldn't be available to us in the West.

How I became a "champion" of leg lengthening is an interesting story. I'm a pretty uncompromising person who likes to win and likes to be the best. I've had a great education, a fantastic career that has made me a millionaire, and a wonderful lifestyle, but my height was just "average" and I found that unacceptable.

I hadn't heard of anyone who had considered or undergone LL with motivations similar to mine, and so I started "Make Me Taller" as a forum for my views and my story, and quickly discovered that there are hundreds-if not thousands-of people who, like me, want to be taller, even though they aren't short.

When undergoing my treatment, I met actors and models who needed a few extra inches for their careers, and even a glamorous grandmother who just wanted to be taller and slimmer so that she could enjoy the rest of her life.

My forum was the first place where such people could come to together to discuss the doctors, the procedures, risks, their thoughts and all manner of things related to LL. We have over 1,100 members now, and get about 25,000 unique visitors per month, which gives an indication of how much interest there is in it.

My adventure started about three months after I discovered that it was even possible. I jumped on a plane to Beijing, had my operation two days later and five months later I was 180 centimeters tall instead 173.5!

BH: You've undergone one leg-lengthening procedure and are now, as I understand it, contemplating another. Some criticize the cost, pain and recovery time associated with leg-lengthening surgery. Have you found, after your first surgery, that the benefits outweigh those issues?

MMT: I think that a lot of people imagine that LL will be considerably more painful and inconvenient than it is. Don't get me wrong-some people find it quite painful, but I was one of the lucky ones who had very little pain and the end result certainly outweighs the temporary discomfort.

Even if it had been more painful, I wouldn't have had any regrets-becoming taller has had an amazing impact on my life.

It's something that only a person who has undergone LL can understand, but when I shake hands with someone that used to be taller than me, and find myself looking down at them, it makes me feel great-as shallow as that is. It's a buzz that hasn't worn off yet, even though I've been back home in England for several months.

I'm going back for a second operation for two main reasons:

1) My first one (external with the Ilizarov frame) went so well, I have very few fears about the second;

2) A lot of our forum members wanted someone they could trust to undergo internal LL with [limb-lengthening surgeon] Dr. Mitkovic so that they could decide whether or not they wanted to do it. In this respect, I'll be something of a guinea-pig, but I will also be able to give doctors and potential patients an interesting insight into how the two different methods compare.

Of course, I am also looking forward to being a couple of inches taller too-my second operation will make me just under 6'1," which I would never have dreamed possible even a year ago.

BH: The internet is now full of advertisements and websites touting mostly useless height-increasing interventions, and the Make Me Taller forums have seen an explosion in membership and media interest over the past year. To what do you credit the growing interest in height enhancement?

MMT: I think that the growth in interest in height enhancement is a sad reflection of how shallow our modern societies have become. Undoubtedly, our physical appearance is of immense importance when it comes to our careers, love lives and even friendships-and height is an important factor.

There is a wealth of research available that supports the view that taller men are more attractive to the opposite sex, and to potential employers, and my personal experiences have shown me that being even a couple of inches taller can have a profound and positive impact on the way that others perceive you.

That said-and this may seem strange coming from a "champion" for LL-I think that it is a shame that our societies place so much of an emphasis on physical appearance, particularly when it comes to important decisions. For example, it's pretty insane that Americans seem to be more likely to choose their leader based on a candidate's height than on their policies!

BH: Ethically, some might argue that height is a positional good, because if everyone got taller nobody would have an advantage. How might you counter such arguments to uphold the value of height enhancement?

MMT: I don't dispute that if everyone got taller that the value of height enhancement would be diminished. However, demand far outstrips supply and we've seen the doctors increasing their prices significantly over the last 12 months, with further increases forecast.

Some countries have even outlawed the procedure, and there are only a handful of doctors in the world who have the experience and the facilities to do it safely. As such, this will never be mainstream-it will remain for a privileged few who are wealthy enough, brave enough or just plain stupid enough to do it!

To help illustrate that, we have over 1,100 members, most of whom are pretty active. However, of that audience, less than 32 have had or are in the process of having LL.

Some doctors have told me that for every 1,000 enquiries they receive, they only end up with one patient-not everyone can afford between $25,000 and $250,000 to have it done, and then to take six months to a year off work to recover.

BH: What do you foresee for the future of height-increasing interventions? Do you anticipate that biotechnology or more advanced surgery will make current procedures obsolete? Are you aware of any research in this area?

MMT: I know that there is a lot of interest in biomedical and noninvasive solutions to height increase from people who would like to be taller, and I've even asked been to get involved in some of those initiatives myself. However, I don't believe that there is a large enough market to justify the kind of investment that would be required to make them viable, assuming that it was even possible.

I do not believe that there will ever be a biomedical solution to height increase.

For example, the Achilles tendon can withstand forces up to 64 times the weight of the average human body-some people have talked about new technologies that can grow bone, but I think it would be physically impossible to grow bone without the soft tissues (muscles, blood vessels, nerves, tendons) being grown and stretched in some way too. How this could be achieved without some mechanical involvement, I don't see. Even with three kilograms of steel wrapped around your leg and with pins inside the bone, the doctors need to monitor carefully how the bone is growing to prevent alignment problems.

Currently, there are no serious pieces of research under way, although some scientists are considering putting together research proposals. At best, I imagine that such solutions are at least 25 years off-assuming that we see them ever.

As far as the existing techniques are concerned, I expect there to be improvements in pain-management, infection prevention and scar recovery, but the technology is already nearly 50 years old and hasn't changed very much.

BH: If you had a child that was shorter than average, would you encourage or allow him or her to have height-increasing surgery?

MMT: I would never encourage anyone to consider LL. However, if I had a child who was determined to do it, then they would have my full support to ensure that they did it in the safest way possible. I know how strong the desire to be taller can be, and I wouldn't stand in the way of anyone who found themselves driven by the burning desire to be taller.

BH: If you believe in the procedure and in promoting its use, why do you request anonymity in your forums and in media interviews? 

MMT: I insist on anonymity on the basis that pretty much all of our members acknowledge know that with this, and many other forms of cosmetic surgery, there is still a considerable stigma attached!

With keynote speakers William Shatner, Ray Kurzweil and Aubrey de Grey, this year's TransVision conference promises to be the best yet. Focusing on nothing less ambitious than "saving humanity," the World Transhumanist Association's annual conference will cover everything from sustainable energy to antiaging medicine. To get the details, Betterhumans Editor Simon Smith caught up with James Hughes, Secretary of the WTA and Executive Director of the Institute for Ethics and Emerging Technologies. Engage.

BH: So, another TransVision approaches. With how many TransVisions have you personally been involved?

I organized the first TransVision I attended. After we elected our first Board of Directors in the winter of 2002-2003 we organized the 2003 TransVision at Yale University, since Nick Bostrom was teaching there at the time and we could get some benefits through sponsorship from the Yale folks.  I was the main organizer, and it was pretty successful, turning a profit and bringing about 100 transhumanists together with about one hundred non-transhumanist folks doing or interested in bioethics.

BH: In what ways have the conferences changed in nearly a decade since they started?

The first couple of TransVisions in Europe in the 1990s were small gatherings for a couple dozen transhumanist guys to meet and bounce ideas off one another. Then TV03 at Yale kicked that up to the 100-200 attendance mark, based around an academic conference model that held through TV04 in Toronto, TV05 in Caracas and TV06 in Helsinki. I don't want to make a prediction about how many we'll have at the gala event we're going to have in Chicago, but it promises to kick us up to yet another level, with carefully selected speakers, professional conference planners working year-round, real (as opposed to transhumanist) VIPs like Shatner and Arianna Huffington. It's going to be cool.

BH: TransVision 2003 was particularly significant in being held at a major university campus, Yale, and in raising public attention of issues and developments in cutting-edge science and technology. Looking back, what would you say were that conference's big successes and failures?

The strategic focus of the 2003 TransVision was to draw in friendly bioethicists and philosophers to meet our community, and orient our community to bioethics as a contestable terrain for transhumanist ideas. Most transhumanists, I think, believed bioethicists were uniformly opposed to the H+ project, while few bioethicists had heard of transhumanism, and those that had thought we were a nutty fringe. We needed to demonstrate to the H+ that, in fact, most bioethicists were closer to us than to Leon Kass, the President's Council and bioconservativism, and to the bioethicists that transhumanists were radical but serious thinkers. I think that meeting succeeded, and we continue to see its fruits as the folks we met there have gone on to write about us, join our projects, and invite us to their meetings and projects. Transhumanism is now recognized as a popular and influential player in the bioethics/biopolitics terrain, and not just a Star Trek fan club.

BH: How have things evolved since TransVision 2003? Do you still find the topics raised there as relevant? Have newer issues supplanted those that were big issues then?

The focus of TransVision 2004 in Toronto was to raise our flag in the cultural and artistic arena, which is lot bigger and more diffuse. The meeting itself was an unquestioned success for the participants, despite being a little smaller than 2003. Stelarc and Steve Mann were amazing and complementary evening speakers, the transhumanist film festival was fun and memorable, and again we met a lot of interesting folks who have become biopolitical allies, like the body modders. Whether TV04 was as successful raising the H+ profile in the arts is harder to say, but we have certainly seen a growing use of the terms transhuman, posthuman and so on in the arts.

TransVision 2005 in Caracas was focused on futurists and the developing world, and had some memorable highlights. It was held in a theater that opened onto the hotel bar and pool, and each participant got a free bottle of rum which made the loose and frenetic organization of the event quite tolerable. Most of the attendees were Venezuelan, but the H+ activists present did get a chance to meet some prominent people in future studies, and it seems like the World Future Society meetings are increasingly infused with H+ speakers.

By comparison to Caracas, Helsinki in 2006 was a well-oiled machine. The Finnish Transhumanist Association is probably our best organized chapter worldwide, and they were able to get the meetings broadcast real-time into Second Life, and posted as video almost immediately on the web. The local chapter folks did a great job at making all the international guests feel welcome, and I got to hang out naked in a Finnish sauna. We met a lot of Europeans there who have gone on to make big waves, such as the Italian Transhumanist Association which is now an active participant in Italian politics, and the Russian Transhumanists who have briefed the Russian government on futurist issues.

BH: TransVision 2007 looks to take things up a notch, with three high-caliber and well-known keynote speakers in Ray Kurzweil, Aubrey de Grey and William Shatner. How does this conference most differ from previous? How has organizing this conference differed from organizing previous conferences?

TransVision 2007 is the first to receive significant philanthropic backing, which allowed the planners to hire a professional conference planning firm, secure top-notch speakers, like Shatner and Huffington, and exciting venues, like the Natural History Museum where the awards ceremony will be held. It's a bit of gamble since the registration fees have taken a jump, and the meeting is still a hard sell to a general audience skittish of an -ism they have never heard of. But hopefully it will all come together.

BH: Some might question the involvement of Shatner, who's known more for his association with science fiction than for any association with science and related ethical issues. What drove the organizing committee to include Shatner as a keynote speaker? How did he react to this request?

I wasn't involved with the invitation, but I understand that Shatner is an acquaintance of Kurzweil's and is generally a supporter of futurism and techno-evolution. I'm looking forward to hearing him.

BH: What can people expect at this year's conference? What aspect of the conference are you most looking forward to?

The theme of this conference is much grander than the previous ones-how can transhumanism solve humanity's problems? So I think we'll hear from both the policy wonky and the radical futurist parts of transhumanism, and perhaps less from the academic and philosophical parts. Otherwise, I'm trying to maintain Zen mind-no expectations.

BH: Given the caliber of keynote speakers, the sexiness of the subject matter, and the location, has the conference attracted more interest than previous conferences, particularly from the media? Are you expecting more media coverage than in previous years?

Absolutely. This should make a much bigger media impact than the previous meetings, and there will also be several documentary film crews there to capture the events.

BH: For people who don't know about transhumanism or TransVision conferences, how would you describe this event in a way that would entice them to attend?

All the leading lights in transhumanist thought and activism will be there. If you are new to the area, you will learn a lot and meet all the principals in the flesh. If you are an old timer, it will be one of the coolest H+ parties ever thrown. Chicago is one of the great cities of the world, and the WTA probably won't meet in the North America for another two years. Be there or be square.

The Singularity Institute for Artificial Intelligence has created a video to educate people about the challenges, opportunities and risks of creating general artificial intelligence: