 All right, let's, why don't we take our seats here and we'll begin the panel here in just a second. All right, let us begin here. Thank Dr. Hayflick once again for his remarkably clear explanation of molecular biology. And as is our custom, we'll begin with asking the members of the panel if they have comments or questions and then we'll get to the questions from the audience. Who would like to lead off? Dr. Selcoe. Well I'm enormously excited and impressed by what Len Hayflick has shared with us and I think it's as clear and compelling an argument as can be made for the importance of the study of the fundamental mechanisms of aging. And so I think that he laid the arguments out very clearly, particularly in my area of interest and that is age-related disease or disease that occurs more commonly in late life. And that distinction is very clear to me and even more clear thanks to his lecture. But I would say this and that is, I think for all of us in the audience, while one can support the importance of basic research on the aging process with statistics such as those that you have described, such as the fact that curing cancer would only add 2.9 years, I think the figure was there's something along those lines curing Alzheimer's might only add 19 days. Those statistics while valid don't speak to the point that for the individual who has cancer or the individual who has Alzheimer's, the increase in life expectancy is much greater. So that is a population statistic. And so I would say that while I certainly understand those numbers, I think the reason that our society has evolved a system for doing a lot of disease related research relevant to aging is because on an individual basis and some of those important individuals include members of Congress, the numbers are much more, the numbers are much greater than the population statistics imply. So that's a sort of a comment. Okay. How can you disagree? Any help from over on the other side there? Actually, I have a question. First of all, I also greatly appreciate the presentation that Dr. Haiflich gave and I was one of those students in the front row by the way, and will always be one of those students. I'd like to ask Dr. Haiflich the question that my professor, Bernice Newgarden, asked me many years ago, which got me into this field to begin with. This was back in the late 1970s. Should the government increase its funding of research on the fundamental biological process of aging for the purpose of extending the duration of human life? Well, the short answer is no, especially if the government is involved. No, but Jay seriously, Jay does ask an important question that needs to be answered. And he and I and others here have kicked this question around for years. And let me put it on the simplest basis that I can think of. Let's argue that some of us sitting here did indeed develop a white pill that you take each morning once a day has absolutely no side effects and is capable of doing one of the following. Slowing down the rate of aging, stopping the aging process. I was going to say reversing the aging process, but let's exclude that. I think that's more science fiction than science fact. But let's assume that this white pill can do one or both. Slow the aging process down or stop it completely. Now you have this pill in front of you with all the guarantees that I made. So the question, there's several questions. First of all, when are you gonna take it? And second, and usually the answer to that is, well, I wanna take it when life satisfaction is at its greatest. Well, the response to that of course is you've gotta pass through that phase of life when it's greatest in order to understand that it was greatest and then return to take your white pill. So you've got a big problem. Then you start to think, well, she was, you know, if I take this pill and my kids don't, someday I'm gonna be as old as my kids. And you can go through this list of bizarre scenarios, all you like, and you really can't come up in my judgment with a scenario that makes sense, even though I've given you the ultimate opportunity to deal with your aging process. One of the things that I think people forget, and I'm going to remind you, is that in this country we have, and perhaps some of them are in this audience, what we call gerontological cowboys and cowgirls. They're retired, they're septuagenarians, they're octagenarians, they've invested in an RV, their kids are all married, they have no responsibilities for children, and they spend the summers in Canada and the winters in Florida. And if you ask them whether they should have taken the pill when they were 40 years old and struggling with raising kids and trying to meet their monthly budget requirements, they would think you're crazy. They will tell you that this is the happiest time of their life, despite the fact that they may have some minor, in most cases, minor medical problems. Everybody who grows old is not sick, and you may be denying yourself the best part of your life. Well, I could go on and on, but I won't on this particular issue, but Jay does raise an important issue. Dr. Whitehouse? Let's go to the audience. And the first one is, tell us about these alligators that don't age very fast. Well, I've never met one, but... It's a very interesting story. And again, to give you some idea of the stone age level of our understanding in this field, it's only been within the past year, or two or three, to be liberal, that we are beginning to pay attention to this observation that's been known for decades, if not centuries. And that is, I'm sorry, the class of animals that do not reach a fixed size in adulthood. And I named a few earlier. There are, the best example are deep sea cold water fish. Some of you have eaten a fish called Chilean sea bass. You would not have eaten it if its real name had been disclosed to you before the restaurant tours changed its name. It was called the Patagonian Toothfish. And because there are no laws or rules about what a restaurant owner or a grocery store owner can name a fish, you can name it whatever you want. Now that we have developed a taste for that animal, it's been discovered about two or three years ago that this fish is a member of a deep sea cold water fish whose aging process is negligible. A dinner-size portion of Chilean sea bass is about 100 years old, and we don't know anything about its biology and its threatened species. Fortunately, in my, I'm going to use the term Progressive City of San Francisco, the restaurant tours do not sell this fish. And of course this is voluntary, you can't demand that people do this. But I make this point to illustrate the level of our ignorance. Apparently the rate of aging varies so that you have extremely low rates of the occurrence of age changes in the animals that I've described. And then you also have some intermediate rates of aging and then you have rapid aging, if you want to call it rapid aging, in mammals in particular. The other serious problem that I should mention before I shut up, is that we have no what are called biomarkers for aging that everyone agrees are acceptable. And by that I mean, how do you measure the age of an animal? You can't measure its length in most cases, sometimes you can, it's very crude. We don't have, even for humans, we do not have biomarkers for aging. I can't walk up to someone in this audience and say with a very much confidence that I know their age plus or minus two or three years because you have no markers. It's guesswork. And we need biomarkers to measure quantitatively the rate of aging in animals. And we don't have it because it hasn't been studied. The question is that the pre-conference material quoted you as saying that cancer cells are immortal. Could you please elaborate? That's like asking me, what is the meaning of life? Well, cancer cells have evolved a mechanism for immortality that we think only within the past 10 or 15 years we understand a little bit. Prior to that we didn't understand it at all. But unlike normal human diploid cells that were described during the introduction that do have a finite capacity to replicate as do all normal cells, human or otherwise, cancer cells, and this was pointed out in my original paper in 1961, that cancer cells, unlike normal cells, are immortal at the time we didn't know why. Now we think we know why, and let me be as brief as I can. The reason for this goes back about 15 years when it was discovered that the tips of chromosomes, I illustrated a chromosome at least on one slide, looks like a big X, at least for most human chromosomes, at the tips of those chromosomes, it was determined that there is an entity called a telomere. The function of that end tip of the chromosome was unknown until about 10 or 15 years ago. A Russian biologist by the name of Alexia Levnikov, who was interested in this problem of why normal cells only have 50 population doubling capability, human cells, also was intrigued by another puzzle in biology, and that puzzle was that the DNA molecule, the main molecule that contains your genetic information, when it copies itself, as you know, what does copy itself, the copy that it makes is shorter than the original. I won't go into the complex biochemistry, but that was a fact. People couldn't understand this, because if the DNA becomes shorter and shorter each time it replicates itself, you're gonna lose genes, and we knew that didn't happen. The Russian Levnikov in an armchair speculation that actually was provoked by his entering Moscow subway station and suddenly having a profound insight, he thought that the subway tracks looked like DNA, in fact it does have some resemblance, and that the engine and the cars were the enzymes that were replicating the railroad tracks or the DNA, and he reasoned that if the engine was incapable of replicating the tracks, but only the passenger cars were, then each time the train stopped at a station there would be more and more loss of railroad track, and he said the way you prevent this is to put in additional track, which of course is an obvious conclusion, but when it comes to DNA he argued, we will put, or at least he speculated that at the ends of chromosomes are nonsense DNA sequences that do not contain genetic information, it's just plain nonsense, but they're there to act as a kind of buffer so that every division of the cell, part of this tip is removed, no problem, has no information, nobody cares, but when it reaches a particular short length, the cell then stops dividing, and that was his explanation for my laboratory finding, and it turns out the guy was right on target, I won't go into all the details of the experimental results that occurred after that, but it was proven that Lovnikov speculation was right on target, furthermore, and this will answer the question, I'm sorry to be so long, but you had to know that in order to get the answer, the answer to the question in respect to immortality of the cancer cells is that they switch on an enzyme called telomerase, which at each division of the DNA, tax on to the ends of the chromosome the missing pieces that would have otherwise developed, so the cancer cell chromosome stays constant in length, it doesn't decrease at each division, it stays rigid and constant, and that is why that cell is immortal. Sorry. All right, here's another one. Dr. Hayflick stated that aging is not determined by genes, what is the role of environmental factors in aging? Well, I could give a snide answer to that question and say that you can avoid aging by killing yourself at the age of 30, but I won't say that. I don't think anybody has actually demonstrated specifically and without question, an effect of the environment on a specific process of aging. That is an extrinsic act, an extrinsic cause as distinguished from intrinsic causes, that is causes within your body. I don't think that things like, and I'm talking now only about humans, this statement is not true for other animals, but temperature changes, changes that don't have an effect on pathology, and that's key for me to say initially, but only changes that have to do with fundamental aging process, I don't know if anyone, somebody on the panel does. Dr. Selk, in that regard, what about UV radiation in the sun for age spots, which I thought you listed as a function of age rather than a disease? Yes, but I'm not sure that I would accept, I doubt you would either age spots as being a particularly good biomarker of aging, and as a quantitative measure of whether UV is affecting the underlying process, I think that would be a rather poor choice to measure. But it would be an example of a potential environmental factor that is associated with changes that. Oh sure, there are lots of those, but they don't threaten life. Right. There's another one here. If aging is in large part really is due to getting rusty, why shouldn't antioxidants help delay the process? Probably because they don't get to the site of action. There's no evidence that antioxidants even cross the gut in humans. People take a bunch of antioxidants, but I don't know of any evidence that they pass the gut. So if they don't get to the site of action, they ain't going to work. It's also true in animals. I don't know of any, that there are some random experiments that show the effect of antioxidants on aging in laboratory animals, but it has never been nailed down with certainty. Len, I guess that depends on what you mean by an antioxidant because many people would ask you about vitamin E, for example, which does get absorbed and actually there's some evidence that gets into brain. The evidence that it helps diseases like Alzheimer's disease is rather weak and getting a bit weaker, but there are a whole wide range of antioxidants, I guess you could say. I don't know of any one that has been demonstrated unequivocally to slow or stop the aging process. No, that I would agree with. Would you think it's theoretically possible? Theoretically, anything's possible. No, no, no. How do you think stem cells research will affect longevity possibilities? I think it's most immediate effect will be on the pocketbooks of the entrepeneurs who invest in stem cell biology. But if the real question behind that question is parts replacement, then I think we can only go so far. Jay and I have talked about this many times. Let's assume that you do have stem cell successes and you can replace whatever you wanna replace. I don't care what it is. And now you have that capability. You've got two problems. First of all, if you replace everything, you don't have what you originally had in the beginning. It's not there anymore. If you buy a car and over a 15 or 20 year period you decide to replace all the parts, do you have the car that you had 20 years ago? I don't think so. So that becomes more of a philosophical question. But the one thing that troubles me in respect to the parts replacement argument is replacing your brain. If you're gonna replace my brain with a younger brain, then I've lost my sense of self and I've lost my memory and I've lost everything that makes me me. And likewise, you, you, if you decide to have your brain. So the exercise becomes pointless. Now some far-sighted cyber gurus have argued, well, you can upload the contents of your brain to a mainframe and then download it to another brain. I don't know whether what I'm about to say is going to upset some people in this audience, but I think I'm gonna say it anyhow. Ray Kurzweil made that remark, by the way. I don't even know Ray Kurzweil. But my reply to Kurzweil was, I'll be darned. If I want to be looking out of my monitor when a drop-dead gorgeous girl walks by and I'm stuck there with a hard drive and a small mouse. Mr. Chairman, I'm beginning to wonder, is it all bio-gerontologists that are obsessed by cars and sex? Hopefully, yes. I think this might be a good time to take a break.