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Thursday, December 12, 2002

Session 2: Duration of Life: Is There a Biological Warranty Period?

S. Jay Olshansky, Ph.D., Professor, School of Public Health, University of Illinois at Chicago, and
Senior Research Associate, National Opinion Research Center, University of Chicago

CHAIRMAN KASS: Can we get started, please? Council Members should have at their seats now a map of where we're meeting this evening for dinner. It's just a block away from the hotel, straight north on 7the Street, and information is there. Again to repeat, warm welcome to Professor Jay Olshansky, who's going to give us the second presentation on the subject of aging research and its implications. Please.

DR. OLSHANSKY: Well, first of all, I want to thank you for inviting me. I think you're going to discover that Steve and I really don't disagree on too many things, but we'll disagree on a couple. And I'm also delighted to hear that there are students in the audience. I feel very much at home with the students in the audience, so it's wonderful that you're here, and I will be speaking to you to some extent.

Now I know the title is, "Duration of Life: Is there a Biological Warranty Period?" That's related to some work that my colleagues and I have done recently, but it will all relate to this basic issue that you have raised in this meeting.

Now these are the questions you have asked me to address, and I'm going to address them all. I'm going to address some a little bit more than others, the issue of life expectancy, first and foremost. I'll spend a bit more time on that, the hard physiological barriers. I'll spend some time on that. Demographic implications of life extension, a bit less. Breakthroughs, and then the position statement on human aging that we published during the summer, I will be discussing this.

Now let's start out with definitions first. I think it's really important that our language be correct, we use the proper language when we discuss these issues, so I'll start out with some basic definitions. Life span is defined as the verified age of death of an individual, which ranges, of course, anywhere from moments after a live birth to the world's record for longevity, in this case I'm showing you a picture of Madame Jeanne Calment, who lived for 122 and a half years. So the life span is the duration of life of an individual.

Maximum life span is the longest life span ever recorded for a species, so again Madame Jeanne Calment would be the maximum life span for humans, but it is one individual in a species, longest lived individual, and this number can only increase.

Life expectancy is - and I'll be showing you an image of this in a moment, it's the average number of years of life remaining for individuals at a given age, assuming that age-specific mortality risks from a life table remain unchanged, and what we refer to as period life expectancy is what's most commonly used. A bit more on that in a moment, because you did ask me to tell you briefly how it's calculated, and actually it's pretty important to understanding the prospective changes in life expectancy.

All right. What life expectancy is not, and this is what you will see often reported in various places. The incorrect definition is the average age at death. It is not the average age at death. Indeed, it is a number that is based on death rates observed for a population, and applied to a hypothetical cohort of 100,000 babies. And I'll show you what a life table is. How is it calculated? All right. So I know — I'm not going to go through this, of course, but I figure you should at least see a life table, and see what it looks like, because this is the basis for the measure of life expectancy.

Now what I did in the next figure — incidentally, by the way, I finally found another use for my dissertation which was published in 1984, because this figure comes out of my 1984 dissertation. It was sitting next to me when I was drafting this, so I scanned this, and here's the second use. This is a truncated version of the same table, and I just want to illustrate a couple of things here.

First of all, this column here, this M(x) represents death rates or condition of probability of death over here, and this L(x) represents this hypothetical cohort of 100,000 babies. And you basically apply the death rates to the babies. You generate a number of deaths, and then you subtract it from that to get down to the next age group. Basically, the measure of life expectancy itself is based on something known as person years of life. When an individual lives one year, that's one person. For a hypothetical cohort of 100,000, we estimate the number of person years expected to live. You divide it by 100,000, and that's your measure of life expectancy, so this cohort of 100,000 people, babies born in a given year would live this many person years. You divide it by 100,000, and that's how you arrive at this number, so it is not an average age at death. It is a hypothetical number, and the critical assumption to remember about life expectancy is the underlying premise that we assume that the death rate is observed in a given year, the year in which you're measuring life expectancy will not change for the duration of the lives of the babies born in that year. So, for example, for white female babies born in 1978, the presumption is that when they reach the age of five, that will be their observed death rate.

Well, under conditions of declining mortality, as you might imagine, this will under-estimate the observed life expectancy of these individuals. And just as a way to illustrate, we've actually been able to calculate what's known as a cohort life expectancy for the babies born in 1900 in the United States based on how long they actually lived. And when you compare the cohort life expectancy to the period life expectancy, the difference is about two and a half to three years, so it really wasn't that large in terms of — I mean it's not 20 years. It's relatively small in terms of magnitude, but there is a difference, just so you know.

Finally, aging versus senescence. When you think of — the word "aging", I know is used most often, but biologists tend to use the concept of senescence to describe what's really happening. Aging, we tend to think of, at least I tend to think of anyway, more as the passage of chronological time, so we all age at exactly the same rate. But we can senesce or grow old biologically at different rates, and this is a classic example of two genetically identical twins, who appear. This one on the left has Alzheimer's Disease, this one does not, as a way to illustrate that even among genetically identical organisms as a result of stochastic random events that occur, stochastic events that occur during the course of life, we can senesce at different rates.

All right. Why do we live as long as we do today? What led to this first longevity revolution? Why is life expectancy now up in the high 70s in humans? Well, this is — it's actually fairly straightforward to explain this. For the vast majority of human existence, birth rates and death rates were always extremely high, about 50 per thousand population. Right around 1850, death rates began to decline very rapidly. Birth rates then followed until we reach this point today, which is referred to by many as the fourth stage of the epidemiologic transition where birth rates and death rates are extremely low, about eight to ten per thousand. And this is the reason both why we have population aging, and individual aging. It's a transformation that occurred principally within the last 150 years or so.

One of the consequences of that dramatic difference in birth rates and death rates, we all know is global population growth, one of the areas, one of the reasons why I came into this field to begin with, but we also have dramatic population aging. This is referred to as an aging pyramid. It's nothing more than a snapshot picture of the number of people alive at any given age, in a given time period. This is for the entire human population in 1900. It was pyramidal. This is fairly common that you see among most forms of life, a large number of young, and a very few make it out to extreme old ages. And now in the developed world, we have created a much more tectilinear or square like age structure where it is looking — it's no longer pyramidal. You don't really see this anywhere in animals living in the wild. It's really unique only among human laboratory animals, zoo animals. That's about it.

So why did life expectancy rise so dramatically during the course of the 20th century? Well, if you remember that hypothetical cohort of 100,000 babies that I was talking about before, if you plot out the ages at which they all died based on the death rates observed in a given year, you would get something referred to as a distribution of death. It was the D(x) column of that life table. And if you plot them all out, you get something that looks like this. The area under the curve is the same. This is the distribution of death for U.S. females in 1900. This is the distribution of death for U.S. females in 1985. It is a classic illustration of a redistribution of death from the young to the old.

In other words, the vast majority of this increase in life expectancy from 47 to about 77 through 80 now for females in the United States, is a result of declines in infant, child and maternal mortality. That can only be achieved once for a population. Once it is then achieved, the only way to achieve another increase in life expectancy like that is to influence the elderly. It's a totally different ball game.

I decided to show you this figure to illustrate changes that have occurred in these various parameters. This is just based on U.S. data. Maximum life span based on U.S. data appears to have increased a little bit. I know that there was mention earlier of dramatic increases in maximum life span. I really disagree. I don't think there have been dramatic increases. There have been fairly moderate increases, and I'm not even sure if there have been increases, quite frankly, because we can't really measure the age of everyone on earth. And so it's possible that a thousand years ago we may have had people over 100. I don't know that for certain.

Modal age at death has increased from 73 to 88. Period life expectancy increased from 49 to about 80. This is just for U.S. females, just to give you an illustration of how these numbers have changed as a result of this transformation in the distribution of death.

This figure illustrates the proportion of the gain in life expectancy associated with changes in death rates at different ages. Again, it's a classic illustration, 1900 to 1910. The majority of the gain in life expectancy was associated with declines in mortality at younger ages. And now between 1990 and 2000, the majority of the gain in life expectancy is associated with the population over the age of 45.

All right. Years ago, my colleagues and I published this article estimating the upper limits to human longevity at about 85, and when we published this article, a number of people disagreed with us very openly, saying no, no, no. Things are going to go much, much higher than you anticipate. Our projected life expectancy at 85 was 88 for females and 82 for males. And it will be evident to you why we came to that conclusion, and then we followed that up with a piece ten years later. What we decided to do was to wait ten years to see whether or not the data were moving in the direction that we had predicted, or whether the data were moving in the direction as others had predicted, which was a much more rapid pace than what we had suggested. And we published our findings last year, which I'll go through very briefly in a moment.

Now previous estimates of the upper limits to human life expectancy have all relied on efforts to answer a single question, and that is, how low can death rates decline. We reversed the question. We refer to it as reversed engineering approach, and instead asked how low do death rates have to decline in order to achieve a life expectancy of anywhere from 80 to 120 years. Fundamentally different approach, and this was the conclusion that we came to. This is one of the figures from our original 1990 article.

Now it's life expectancy at birth on the (X) axis, and percentage reduction in mortality on the (Y) axis required to produce these higher life expectancies. So for example, in 1985 female life expectancy at birth was 78.3, 71.2 for males. In order to achieve a life expectancy at birth of 85, you simply go up the axis and go over. You could see it would require about a 50 percent deduction in all causes of death for females, and roughly a 70 to 75 percent reduction in all causes of death for males, just to get life expectancy up to five.

Now to provide some perspective, we calculated hypothetically what would occur with the elimination of various diseases, major fatal diseases in the population, and the vast majority of all humans die from heart disease, cancer and stroke. And we show here that if, indeed, we were to find a cure for cancer, for example, life expectancy at birth would rise by about three and a half years. Life expectancy at birth would also rise by about the same amount, three to three and a half years if systemic heart disease was hypothetically eliminated. And if we eliminated all cardiovascular diseases, Diabetes and all forms of cancer combined, life expectancy at birth in humans would rise up to about 90. So you have to believe that we will be experiencing rather dramatic reductions in mortality in order to yield these very high life expectancies. A life expectancy of 100 required about 85 percent reductions in all causes of death at every age, so when somebody says life expectancy is going to go to 100, this has to happen in order for life expectancy to go to 100. An 85 percent reduction in mortality at every age, which is the reason why we didn't believe it was possible or likely.

We then followed this up with research ten years later. We used data from three of the longest lived populations, the United States, France and Japan. Indeed, as we had anticipated, there was not a dramatic change in the probability of experiencing these much higher life expectancies, even though there were changes in life expectancies during this time period. We did experience eight-tenths of one year increase in life expectancy at birth for females. I have some other figures that illustrate this better actually.

One of the claims that was made by those who were predicting much higher life expectancies was that death rates would decline at 2 percent at every age for every year for the next 100 years. Well, that's a testable hypothesis, of course, so we took a look at the data to determine whether or not during those first ten years following that prediction, whether death rates would decline by that magnitude. And for the United States, we found if you look at the age group from zero to 99, the magnitude of the reduction was only four-tenths of one year, not — four-tenths of a percent, not 2 percent as had been predicted by those anticipating much higher life expectancy.

Interesting to point out, there were some increases in death rates in some age groups in the United States between 1985 and 1995. There have been some large reductions in death rates in France and Japan. They are not at 2 percent, but they are significant still.

Another way to illustrate this issue of difficulty in raising life expectancy, life expectancy on the X axis, percentage reduction in mortality required to raise life expectancy at birth by one year. So, for example, when life expectancy at birth is 50, it takes about a 4 percent reduction in death rates at every age to raise it to 51. When life expectancy gets up to 80, it takes about a 9 and a half percent reduction to produce the same one year increase in life expectancy. In other words, and this was really the principal message that we were trying to get across with our original article, was the higher life expectancy goes, the less sensitive it becomes to changes in death rates. The higher it goes, the less sensitive it becomes, the more difficult it becomes to raise the measure further, which is actually the reason why we were suggesting that life expectancy is, perhaps, not a very good metric, a very good measure to tell us anything certainly about the health of the population.

This will be the last figure I'll show on this, because I realize I'm beating you to death with this issue of life expectancy, but this is actually an important one, because one of the questions that came up often after this issue first arose was, well, if you were around in 1900 and you were asked the same question, how high would life expectancy rise, would you have predicted that it would go up to 80? And my answer was no. Well, then I've been told how could you make a prediction today, based on what we know today?

Now actually, as it turns out, believe it or not in a way this is a testable hypothesis. The X axis is age, on the Y axis is the proportion surviving. Remember Steve talked about this earlier. This is the same hypothetical cohort of 100,000 babies looking at the survivors now instead of those that died. This is the survival curve for the females in 1900. This is the survival curve for females in 1995, and so we asked the question. We know that life expectancy rose by about 30 years during this time period.

Well, if all of the dramatic reductions in death rates observed during the course of the 20th century were to occur again at every age, this is the survival curve that would result. This is the life expectancy that would result, about 89.1. In other words, about a ten year increase in life expectancy at birth, not the 30 years that we observed during the previous century. And if it all happened a third time, the gain would be only 6.1 years, life expectancy would be 95. It's a way to illustrate that the magnitude of the gain and the increase in life expectancy is decelerating as it goes higher. Skip that.

Now I want to present an opposing point of view. Some mathematical demographers have suggested that life expectancy will go to 100 by the year 2060. And this will happen principally by extrapolating past mortality trends into the future. And this is the figure that has been used. And there's very compelling evidence here that there have been some interesting and dramatic increases in life expectancy observed, steady increases since 1840.

This is record life expectancy observed among humans in various sub-groups of the population, increasing steadily from about 45 or so, all the way up to, the record I think now is close to 85 for Japanese females. And what they're suggesting is, is that if we have observed this increase in life expectancy for the past 160 years or so, that there is no reason why it cannot continue into the future. And so this mathematical extrapolation is the basis for the prediction that life expectancy will go to 100 by the year 2060. And if this is all you look at, if you look only at the historical trend in life expectancy, this is a very compelling argument for why you might anticipate a continuation of this historical trend.

Now this is the actual terminology that is used by the authors. They demonstrated that there's been a two and a half year increase in life expectancy per decade, and therefore, it's reasonable to anticipate that this will continue out for the next six decades. However, I used this same extrapolation method to go backward in time just to see what would happen. And if you go backward in time using the same extrapolation method, life expectancy would be zero in the year 1750. So I have argued, as have some others, that it is no more reasonable to make projections of life expectancy going forward in time using an extrapolation method, than it is to go backward in time. We basically need to understand the underlying biology of humans to make sure forecasts, rather than relying entirely on mathematical extrapolations.

So if there's going to be another quantum leap in life expectancy, we're going to have to extend the duration of life, of people like Madame Jeanne Calment and others who have already lived 70, 80, 90 or 100 years or more by 70 or 80 years, in order to achieve a comparable increase in life expectancy like that observed during the 20th Century. And here's where Steve and I are in complete agreement.

The only way this is going to happen, it's not going to happen by altering our lifestyles. It's not going to happen by ingesting anti-oxidants. It's not going to happen by injecting yourself with growth hormone. It's going to have to happen by altering the basic biological rate of aging itself, which is something we cannot currently do, but researchers are trying to do. And there's one last way to illustrate this point.

You know actually, interestingly enough, Steve, this is the first time I've ever seen you show a figure of running times. Here's mine for the world record for the one mile run, indicating that it's declined steadily, very much like life expectancy has increased steadily in the middle of the last century from about five minutes in 1850, to three minutes and 43 seconds today. So if you do a linear extrapolation of this trend, which is the same method that is being used to generate these much higher life expectancies, you would run one minute — one mile in one minute in the year 2420, and we would do it instantaneously in the year 2580.

Okay. Are there hard physiological barriers to the human life cycle? Now the answer to this question is yes and no, and I'm going to spend much less time on this than I did on the issue of life expectancy, but the yes and no answer, you know, when you say yes and no, some people will only hear the yes, and some people will only hear the no. And I will encourage you to hear both answers, and here's where I get into a bit of evolution biology, which I thought Steve was going to talk more about, but I'll touch upon this issue a bit more.

And it's the issue of why not immortality? Why aren't we immortal? And the answer is, immortality in a way already exists for DNA. And once DNA acquired the property of immortality, its carriers became mortal — you and I.

Now I use this analogy, and have used it for quite some time as a way to illustrate the fairly complex evolutionary theory of senescence. This is the Indianapolis 500 race car analogy. Now we know, of course, what the duration of this race is. It's 500 miles. If something goes wrong with these automobiles during the race, they bring them in, they fix the parts, they send them back out. What's interesting here is that when the race is over, they turn the engine off and they bring the car back into the shop, which is something we can't do in humans. The engine of life is always operating until the end.

If you were to conduct a hypothetical experiment on Indianapolis 500 race cars, where instead of turning the engine off after 500 miles, you continue to operate them, run them around the track until they all failed, you would actually see a distribution of failure times that is very much like that of living organisms, life humans, and mice, and dogs.

The key thing here is that, number one, you would get to see things go wrong with these automobiles that you would never ordinarily have an opportunity to see, because you're operating them beyond the end of their effective warranty period. And the other key point is, is that the engineers in this case did not build in a program for failure. They're simply operating beyond the time period that they were intended to be used.

Well, the same logic actually applies to sexually reproducing species, but the measure — the end of the race is not a measure of distance, it is a measure of time. And in this case, reproductive success includes not just the time period when we are producing offspring, but a time period when we can contribute to the reproductive success or fitness of our offspring as grandparents, so there's a grandparenting period as part of the end of the reproductive period. And in effect, what we are doing to ourselves and other sexually reproducing species is the very experiment that I was talking about with automobiles. We are pushing ourselves well beyond the end of our reproductive window, and we are having an opportunity to see things go wrong with our living machines that we never would ordinarily have an opportunity to see. And the further we push the envelope of survival into the post reproductive region of the life span, the more things we will see go wrong, as well.

Now this is the basic linkage that I know Dr. Kass was looking for on this linkage between reproduction and senescence. The basic evolutionary argument suggesting that natural selection is very effective at influencing gene frequencies in the pre-reproductive period, but as soon as we begin reproducing the ability of natural selection to alter gene frequencies declines very rapidly, as soon as we begin reproduction. The force of selection declines very rapidly, until we reach the post reproductive region of the life span, where the ability of selection to influence gene frequencies declines to very low or negligible levels.

Now this actually is a key figure linking reproductive and senescence. And what I will tell you is, and my colleagues and I have done work in this areas, as well, where have looked at the fundamental linkage between the timing of reproduction when puberty begins, the length of the reproductive window, and the duration of life of a species. And a number of researchers have demonstrated that the duration of life of a species is calibrated to the onset and length of the reproductive window. And we've done this in more than a dozen mouse strains from the Argonne National Laboratory database. We found something similar in humans, in dogs, that there is a fundamental linkage between these biological attributes. And if you're going to alter one, you are likely going to alter the other.

I'm going to skip over — well, actually let me show you. This actually is an important figure. You know, when we talk about death rates, this is what they actually look like. Age on the X axis. This is a semi-log scale, so when there's exponential increases in mortality, you get a straight line here. This is a way to illustrate that there have been — that the age trajectory of mortality really has not changed very much during the course of the 20th Century, even though we have lived much longer. And this actually is an important point, because many of the researchers from the biological sciences who have suggested and have argued that we have altered aging, I believe, have not actually demonstrated that aging itself has been altered, because we can't measure biological aging itself. It has been used as this, the change in the death rate, both the inflection point, the timing with — the age at which the death rate increases, and then the slope of this mortality curve, which is taken as a proxy for aging.

The biological process of aging itself cannot currently be measured, so when somebody says that aging has been altered, or aging has been delayed or postponed, I would say that we don't have definitive evidence to support this particular view. This is what is used, so much of what goes wrong with us as we grow older, as many of us have suggested is not our fault. And senescence is, indeed, an accident of surviving beyond the warranty period for living machines, which is the main point we were making earlier.

Now here's the yes and the no. There is no biological limit to life. Evolution could not have given rise to genes designed for the purpose of killing us, but nevertheless, duration of life is fundamentally influenced by biological clocks that regulate growth, development, and reproduction, and senescence is an inadvertent bi-product of these genetic programs according to evolution theory. So on the one hand no, we don't have a program designed to kill us, but on the other hand we do have programs, very tightly controlled genetic programs for growth, development and reproduction, that have as an inadvertent bi-product of their existence, senescence. And so there can be no aging or longevity genes, nor are there hard physiological barriers to extending the life span, but nevertheless, there are constraints on duration of life that are influenced by both biochemical changes that occur, biomechanical changes. This is an article we published last year of human rebuilt to last in biomechanics, then biodemographic constraints. And this is smaller, but I couldn't find a symbol for stochastic events, but it doesn't mean it's any less important, the stochastic or random nature to the aging process itself.

Now I'm going to spend much less time on this issue, Prospects for Significant Breakthroughs in Aging Research. It is important to distinguish between breakthroughs that modify the biological rate of aging, and breakthroughs that may extend the duration of life. And I think some of these animal models are really modifying the duration of life. Much as we do with humans in altering our risk of heart disease and cancer, one could make the argument that we're altering aging. I don't think we are.

Extension of life can occur without modifying the biological rate of aging. If I was asked to come up with any sort of breakthrough that I would anticipate that would modify the biological rate of aging, I would expect it would come from pharmaceutical industry that alters maintenance and repair functions. I put in slightly smaller letters caloric restriction, emetics, and genetic engineering. I'm less convinced that these will actually work on humans, and we can discuss this later.

Breakthroughs that might extend duration of life without modifying the biological rate of aging, there are plenty of these. There's a whole laundry list of ways in which we can intervene that may extend duration of life without necessarily influencing the biological rate of aging. I know you have personal interest in many of these topics.

All right. Demographic implications of life extension, I'll address very quickly. I wasn't sure which one of these — these are both the same figure, and this one is better, so I'm going to use this one. You know, this is a typical question that students of demography will ask, and so — and I'm not the first one to answer this. It was actually answered by Anthony Cole, a famous economist in the 1950s at Princeton. And so I did some basic calculations to demonstrate what would happen if we achieved immortality today. And I compared it with growth rates for the population in the middle of the 20th Century. This is an estimate of the birth rate and the death rate in the year 1000, birth rate roughly 70, death rate about 69.5. Remember when there's a growth rate of 1 percent, very much like your money, a growth rate of 1 percent leads to a doubling time at about 69 to 70 years. It's the same thing with humans. With a 1 percent growth rate, the population doubles in about 69 years. If you have the growth rate — if you double the growth rate, you have the time it takes for the population to double, so it's nothing more than the difference between the birth rate and the death rate to generate the growth rate. And here you can see in 1900, the growth rate was about 2 percent, which meant the doubling time was about five years. During the 1950s at the height of the baby boom, the growth rate was about 3 percent, which means the doubling time was about 26 years. In the year 2000, we have birth rates of about 15 per thousand, deaths of about 10 per thousand, low mortality populations, which means the growth rate is about one half of 1 percent, which means it would take about 140 years for the population to double.

Well, if we achieved immortality today, in other words, if the death rate went down to zero, then the growth rate would be defined by the birth rate. The birth rate would be about 15 per thousand, which means the doubling time would be 53 years, and more realistically, if we achieved immortality, we might anticipate a reduction in the birth rate to roughly ten per thousand, in which case the doubling time would be about 80 years. The bottom line is, is that if we achieved immortality today, the growth rate of the population would be less than what we observed during the post World War II baby boom.

We would eventually run into problems, of course, a century down the road, but just so you know the growth rates would not be nearly what they were in the post World War II era, even with immortality today. However, it would have a rather dramatic effect on age entitlement programs like Social Security and Medicare. When Social Security was created in 1935, they predicted there would be no more than about 20 million beneficiaries. This is what was actually observed, and their recent prediction, if indeed life expectancy were to go much higher, then we would run into very severe problems with the funding of age entitlement programs like Social Security and Medicare.

If there was another quantum leap in life expectancy, I don't really know how these other attributes of human life would change, marriage, retirement, work, education. I don't know any better than anyone else. What I would anticipate is, is that there would be fundamental differences in all of these attributes of society if there was another quantum leap in life expectancy.

I'm going to end with the position statement on human aging, and I'm only going to touch upon this briefly. This is something we published last year. You might imagine getting 51 scientists to agree on anything is extraordinarily difficult. In fact, as hard as I tried to get Steve to sign onto our position statement, we weren't able to get him to sign on. I will tell you that we didn't all agree on everything that we put into this position statement, but we decided to compromise on some of the language for the purpose of getting across a very important message to the public. And that is, number one, there are no anti-aging medicines in existence today. And number two, there is a great deal of very interesting, fascinating good research ongoing in the field of gerontology designed to understand and modify the biological rate of aging. And we not only support this research, but believe that it's absolutely critical to helping us deal with a much more rapidly aging population. And there was a question associated with this, do the conclusions that we came to in our position statement apply to biomedical interventions? Let me skip — well, actually, I don't want to skip by this.

A number of other publications came out associated with this question of anti-aging medicine. This one came out from International Longevity Center in New York. This is a report that was published by the GAO the week of 9/11, which is why no one saw it, suggesting that anti-aging products pose a potential for physical and economic harm. And I will end by showing you the various issues that we raised during this discussion. I mean, really this position statement grew out of a AAAS meeting that many of us attended about a year and a half ago, where we were discussing for prospects for increasing human life expectancy, and we were lamenting about the problems associated with those selling anti-aging products, so we decided to provide as definitive a statement as we could about each of these issues, about what we know and what we don't know, and whether or not we think that these influence aging itself or duration of life. And so we basically have — we tried to create as short a paragraph as we could on each one of these issues to tell you what we knew, and what we didn't know. And I'm going to end with, I know you don't want to read any of this stuff. And we have published this, but I will point out the very last sentence of our conclusion, which is, for those of you who cannot read this, "Successful efforts to slow the rate of aging would certainly have dramatic health benefits to the population by far exceeding the anticipated changes in health and length of life that would result from the complete elimination of heart disease, cancer stroke, and other age-associated diseases and disorders." So I completely agree with Steve on this point, which is one of the first points that he was making; and that is, is that research on aging is fundamental. If we can succeed in postponing many of the diseases and disorders associated with aging, the benefits would be far exceed those that would accrue, we believe, with the elimination of major fatal diseases in the population. And I think I'll end there.

CHAIRMAN KASS: Thank you very much. We'll get the lights on shortly, but if people are willing to start in semi-darkness, I think I see Robby George's hand. Please.

PROF. GEORGE: Thank you, Dr. Olshansky, for that presentation. One of the figures you had on death rates included, if I saw it correctly, a rather startling statistic on an increase in death rates for persons between the ages of 20 and 35 from the period of 1985 forward. Do you remember that figure? For the U.S., yeah.

CHAIRMAN KASS: You commented on it.

DR. OLSHANSKY: Was it this one?

PROF. GEORGE: No, I don't believe so.

CHAIRMAN KASS: It was the table that you showed with Japan and France.

DR. OLSHANSKY: Oh, this one.

PROF. GEORGE: Yeah. What's the plus one point? I mean, that jumps off the page.

DR. OLSHANSKY: Yes, it should jump off the page.

PROF. GEORGE: 20 to 39, I thought it was 35. It's 39.

DR. OLSHANSKY: 20 to 39, and it's actually — I didn't show this, but there are increases in death rates among some older age groups, individuals at older ages, as well. That's a plus 0.7 percent increase, seven-tenths of 1 percent, a 1.1 percent increase for males probably associated with HIV. But yes, it should jump off the page.

It's a way to illustrate, I think, that — you know, there's a tendency when making forecasts of life expectancy to assume that they're always going to rise. And this issue came up when I was here in Washington a couple of months ago talking to the Trustees of the Social Security Administration about this very issue, about projections of life expectancy. And it is always assumed that they are going to go up, and I have suggested, as have others, that maybe we need to be cautious about this long term projection assuming it's always going to rise. There are sub-groups of the human population that have experienced an actual decline in life expectancy in various parts of the world. Also, at some age groups that there have been increases in mortality, not always decreases in mortality, so you're correct.

DR. ROWLEY: And what's the role of guns and killing with guns in that particular age group?

DR. OLSHANSKY: Well, that's the age window where you would see the effect of extrinsic causes, like homicide and accidents. And clearly, if those are on the rise, you're going to see an increase in mortality in those age groups.

PROF. GEORGE: Do you know if they are on the rise for that period?

DR. OLSHANSKY: Well, for that period they were on the rise, absolutely. This is 1985 to 1995.

PROF. GEORGE: I'm asking whether you know if the murder rate is on the rise.

DR. OLSHANSKY: Oh, I don't know. I didn't break down the seven-tenths of a year, or the 7 percent and the 1.1 percent into the underlying causes. I'm guessing that HIV has contributed significantly to this in the United States, but I don't know about the change in homicide rate.

PROF. GEORGE: But if it were HIV, should the statistics be that out of whack with what's going on in France? I just don't know. We're talking about a rate here.

DR. OLSHANSKY: This is a percentage change in the conditional probability of death, and I just don't — I didn't break it down, so I don't know with certainty what led to the increase in mortality in that age range. But those are real numbers for the United States.

DR. ROWLEY: But isn't homicide the most common cause of death in males, particularly black males, age something like 18 to 30?

DR. OLSHANSKY: I think so, yes. Yes.


DR. FOSTER: There are certain precincts in Washington where the life expectancy of young males in certain racial groups is, you know, like Bangladesh and so forth. But in the current science, there is an estimate in regard to what was just said, that the AIDS is the leading cause of death in the world from Gallow and so forth. There are three articles there.

I think most people believe that it's Tuberculosis. And one of the things, as you may know, and particularly resistant Tuberculosis, I think one of the things that may, in fact, change things unless science is able to deal with this better, is the resistance of organisms that are going to cause a back movement into death. If I were to say, I mean other than the enemy or anarchy in the world that wars are doing and so forth, I would say that is the greatest problem that is likely to move us back, because a great deal of what that early life change and so forth has to do with the antibiotic appearance and so forth.

DR. OLSHANSKY: Yeah. There are two things that I would put my finger on that might change this trend in life expectancy. One would be the re-emergence of infectious diseases, as you were saying. And number two, the obesity epidemic which will eventually be translated into number of late onset diseases in populations. It's actually a paper that I'm just now working on.

DR. FOSTER: Yeah. This is an area I'm very interested in, but the pharmacologic approach to obesity is likely to be much more effective than the things that are going on in terms of, you know, senescence and so forth. I mean, because we already have drugs in the system that I work, you know, you worked out all the details on, that you can dramatically change obesity in experimental animals now by altering activities of one or two enzymes, which you can do with small molecules. So I'd be much more optimistic about curtailing — no, I don't know what it will do in the third world, these things will probably cost too much, but at least theoretically, the obesity problem and lipotoxicity, what we call lipotoxicity, the death of organs, heart and so forth and so on, that's an achievable thing, much more easily achievable than what we're talking about here. So that's why — I mean, if you just looked at it right now, I would absolutely agree with you.

I heard a talk this week that said obesity is the leading cause of death in the world, you know, but I think that's very different than this biological senescence that you're talking about.

CHAIRMAN KASS: Mary Ann Glendon.

PROF. GLENDON: First of all, thank you both for terrific presentations. This question is addressed to you both. We read a lot in popular literature about the implications for the welfare state, this phenomenon of relatively low birth rates and greater longevity even at present rates. And I'm wondering where — if we wanted to look into the implications for health care, for social services, for Social Security, where is that work — where is the best work done? It's an inter-disciplinary field, and I found myself wondering as I was listening to both of you, is this one of the things that demographers do, or do sociologists do it, or political theorists, or is it one of the things that falls between the cracks? I notice that one of your collaborators is from ENAD in France. I understand the French have a wonderful multi-disciplinary demography institute. If we wanted to know more, should we perhaps get somebody from over there, just on the implications for the welfare society.

DR. OLSHANSKY: You know, this is — actually, it's not an area that I address personally, and this is not one of those things where I'd like to give you an immediate answer, but I'd like to go back and find the right people to put you in touch with. There is a lot of very good work on this topic going on in the United States. I think you're right, ENAD is a place where there's a lot of good work going on, but I'd like to think about the answer to this question, and get back to you with the right contacts. Off the top of my head, I prefer not to guess.

CHAIRMAN KASS: Rebecca Dresser. I'm sorry.

DR. AUSTAD: No, I wouldn't really — yeah, I wouldn't really have any — you know, biologists certainly don't do this. One place I think might provide a suitable guide is probably Japan, which has had a more rapid rate of increase in longevity than we have, has greater longevity now, and presumably will encounter all the same problems earlier.

PROF. DRESSER: I wanted to ask about your point that we should de-link increased life expectancy from anti-aging. Those are two different things, if that's what you meant. So I just wondered, is it — I guess two questions. One is, is it a matter of spin so that we might say that what we've achieved now is an increase in aging, rather than anti-aging in terms of success. We have successfully extended the life expectancy, however, instead of talking about this as an anti-aging measure, we could talk about it as an aging increase measure, and that the period of aging has increased.

CHAIRMAN KASS: You mean senescence. Right?

PROF. DRESSER: Yes, senescence.

DR. OLSHANSKY: Well, actually when I was talking about de-coupling, I was talking about de-coupling efforts to modify the biological rate of aging itself, and efforts to alter the manifestations of aging. And most of what we do today is an effort to modify its manifestations.

Some of the work that Steve was talking about and others, is an effort to modify the basic biological process of senescence itself, which presumably would postpone into later ages all of the manifestations of aging. So when we alter the risk of heart disease, or we alter the risk of stroke or cancer, we're not influencing the process of aging. We are actually enabling — or senescence, I should be using my own terminology. We're enabling senescence to be expressed in new ways by pushing people out into the post reproductive window of the life span, and we get to see things that we ordinarily wouldn't see. And I'm not sure if I answered your question.

The de-coupling is between, you know, efforts to go after aging, and efforts to influence its manifestations. Anti-aging, what's known to some as anti-aging medicine, and the claim is made by some that we can alter, that we can slow down, stop, or reverse aging is really nothing more than classic demonstration of the ability to become more physically fit at any age. Whether you're 60, 90, or 100, if you choose to be more physically fit tomorrow than you are today, that is a matter of choice. You can increase your muscle mass. You can reduce your rate of bone loss. You can alter mental acuity and skin elasticity. These are not alterations in the basic biological process of aging, but rather its manifestations.

PROF. DRESSER: I guess this is difficult for a non-scientist. Isn't there some overlap? I mean, for example, your last point you said in terms of research priorities, well, if we put this money into anti-aging research rather than research on various diseases, it would have a much bigger impact. But I mean, aren't some studies on cancer and so forth looking partly at aging? It's just difficult to see how those are totally distinct.

DR. OLSHANSKY: Well, I guess I don't see ongoing research in cancer as an effort to attack the fundamental biological process of aging itself, which influences virtually every cell in the body. So no, I would not see them as the same. If we were to succeed, I mean, let's say we did come up with some sort of pill that we could take that would enable us to postpone aging, then everything that we see that we associate with senescence, with growing older, with basic changes in joints and organs, and tissues and so forth, and its manifestations would be pushed to later ages.

Now we wouldn't necessarily be younger longer. We would be more physically fit longer. I don't know necessarily if we would be living longer. And I'm not sure living longer should be the goal, but living healthier should be the goal. And one of the best ways to achieve that is to go after senescence itself.

CHAIRMAN KASS: Michael Sandel.

PROF. SANDEL: This is not really a question for the presenters, both of whom really informed us in very rich ways. It's an observation, and a puzzlement about what's at stake for us in this question about longevity. We, after all, take it up under the heading of enhancement, and in other discussions of enhancement, sex selection, for example, the ethical questions have been more transparent than they are in this case of longevity.

As I — so the question I'm wondering is, why it's ethically interesting. It's clearly of great social, and economic and political importance for reasons that Mary Ann Glendon's question raised, we were to think about the implications of life expectancy for Social Security and for various other social policies. That's clear. But what hangs on this discussion for purposes of ethics?

And as I understand the ethical concerns that might be lurking here, concerns about the implications of extending life, I've only been able to glean one or two. One of them, I associate with out chairman, who worries about immortality, who wants to make the world safe for death, because immortality would raise fundamental questions about the construction of human meaning and meaningful lives. And I take that point as a powerful insight, and I certainly wouldn't quarrel with it, and perhaps no one would quarrel with it. But none of the research that we've been discussing implicates immortality. It involves longevity. To double or triple, or quadruple longevity short of immortality wouldn't raise those big questions about the meaning of life if there were no death, so this is not implicated.

A second possible ethical implication might have to do with this question of relations among the generations, would the ethical character of the relations among generations be altered if longevity were extended in some significant way. So I can see that as a possible area of ethical inquiry.

And then the third area really doesn't have to do with longevity, as such, but with alleviated infirmities and senescence, the prospect of dying at about the same age, but in the pink, as Gil was saying. And there, the question — Leon has posed this interesting question about whether that might dull our readiness to die, so I understand that question might arise. But apart from those, I don't really see what the ethical issue is, so my instinct is to say longevity, we shouldn't aim at it as a priority for research, extending life as such. I don't see any reason to do that. But neither should we worry about it. If it comes about as the side effect of research that aims at alleviating infirmities and reducing the debilitating effects of senescence. Am I missing something? And as I said, I don't mean this to be directed to — it shouldn't fall on the shoulders of our guest. The Chair can address it, if he likes.

CHAIRMAN KASS: I'll wait because —

DR. KRAUTHAMMER: Why are you assuming that we shouldn't aim at longevity? I thought you said —

CHAIRMAN KASS: He said longevity. He meant immortality.

DR. KRAUTHAMMER: No. Were you talking about longevity as a research endeavor.

PROF. SANDEL: Well, I don't see why there's any particular — given the other important things to aim at in terms of medicine, I don't know why adding numbers of years without improving the quality of life in the last part of — I don't know why that's morally compelling.

DR. KRAUTHAMMER: If we call it postponing senescence, you would say that it's not a worthy goal for research?

PROF. SANDEL: Oh, that would be.


PROF. SANDEL: But they've drawn our attention very well to the distinction between those two things, between enabling people to live longer, and combating the infirmities that go with senescence. I'm all for the second, but I don't think anyone has presented an argument for the first. Have they?

DR. KRAUTHAMMER: No, I'm just trying to clarify what you were saying we were against.

CHAIRMAN KASS: Mike Gazzaniga, please.

DR. GAZZANIGA: Well, just — I know if I'm silent, pretty soon Mike Sandel will ask the question I wish I could have asked, so I second his question, what is it we're doing here on the ethical dimensions of this?

CHAIRMAN KASS: I'm ready, but let other people go first. Mary Ann Glendon.

PROF. GLENDON: I don't know whether this qualifies as ethical. I'm just a lawyer so, you know, we're not famous for being strong in that department. But looking at your description of what happened to longevity over just the 20th Century in developed countries, would it be fair to say that at the beginning of the 20th Century, the dependent population was largely composed of children, rather than the elderly? And at the end of the 20th Century, the dependent population was largely composed of elderly, rather than children. Would that be right?

DR. OLSHANSKY: Well, the use of the word "dependent" is problematic, as you might imagine.

PROF. GLENDON: People needing care. I'm getting back to my interest in the welfare state, that people needing care, people who in varying degrees have to have somebody attending to basic needs.

DR. OLSHANSKY: There is clearly a shift. There's a measure called the Age of Dependency Ratio, which is the proportion of the population over 65 divided by the working age population. And that ratio has increased quite dramatically during the course of the 20th Century. I pretty much object to the word "dependency", because it implies that they're not contributing anything to society, and I would completely disagree with that.

Let me follow on on this discussion here, because the use of the word "enhancement" came up, and I think it addresses the issue that you're raising here, because there are a number of researchers who believe that a dramatic extension to the human life span would be an enhancement, however it occurs, whether it's through genetic engineering, through some biomedical technology that permits us to dramatically extend duration of life. And here's where I would throw out a caution.

I would say enhancement is a word I would only use if we knew that we were extending quality years. And the feel that I have is that we are going to rush head-on into this effort to alter aging without knowing what its consequences will be, what its manifestations will be, both in terms of the health of the population itself that's making it out to older ages, and its influence on social institutions, such as the ones that you're talking about, the contract between the older population and the — the non-working population and the working population. And there — you know, if there's just a minor difference in the projection of life expectancy, just one or two years, the size of the population, the beneficiary population increases dramatically.

When you talk about a 15 year difference in a projection of life expectancy, it's a quantum difference in an effect on entitlement programs such as Social Security and Medicare. So enhancement is a word I would use very cautiously when it comes to life expectancy.

DR. KRAUTHAMMER: But couldn't you rectify that imbalance if you have a large increase in the say non-working population by simply altering our definition of working? I mean, if you get an increase in the over 65 population, and you increase — you raise the retirement age one or two years, you've dramatically altered — you can restore that ratio, so I'm wondering why you would object to a change in what science does, and what science might achieve because of the constraints that are now set by social conventions, which can easily be changed. I mean, Bismark is the one who came up with 65 because nobody lived to be 65. It was a very reasonable way to establish a welfare state. There would be no old people, but it's a long time since Bismark, so that age is rather arbitrary.

I'm just saying if we were to make progress, if we wanted to define it as progress, we can argue about that, I'm not so concerned about the social, at least the economic implications because it depends on certain conventions which are very alterable.

CHAIRMAN KASS: Do you want to comment?

DR. OLSHANSKY: Well, in a way I agree. I think — I mean, my personal concern is more with the health implications. I think that extending the envelope of human survival, combating death by any means is going to push people into an age window where we see things that we don't want to see. And I think the modern rise of Alzheimer's Disease might be in part a classic example of a product of our success. The more successful we are at extending duration of life, the more we are going to see the diseases that are most common among the extreme elderly occurring. This was the point that Steve was making very early in his presentation, and that's the main concern that I have, is the health of the older population.

DR. KRAUTHAMMER: Can I push you on that for a second, if I may? If you were then retroactively reordering history, would you have preferred that we had not engaged in the medical efforts that reduce heart disease and others that have created the epidemic of Alzheimer's?

DR. OLSHANSKY: No. And that question, as you might imagine, I have faced many times. No, I would not ask that we stop our effort to go after the major fatal diseases. All I'm saying is we need to be aware of the consequences of our success. And if we continue to succeed in enabling people with heart disease, cancer and stroke to survive longer with their disease, we may not necessarily like what we see. I'm not saying we should be truncating that effort, we just need to be aware of the consequences of our effort.

DR. KRAUTHAMMER: But you would truncate it if it were not disease-specific, if it were just extending age for its own sake, you'd say no, let's not do that. But if it's preventing heart disease, yes, even though it'll have these consequences.

DR. OLSHANSKY: Actually, I think what I'm suggesting is that not only should we go after the major fatal diseases, and the non-fatal disabling conditions, but also in a way, perhaps more importantly, aging itself. I mean, the entire medical model is very much taking — it's a product of our effort to go after infectious diseases. It's whatever disease is in our face at the moment, and I refer to it as the hurdle approach to disease. You know, whatever is in front of us, we jump over it, only to face another one later on. And the hurdles get more frequent and higher the older we get, and I'm suggesting we push the hurdles back, and that's the effort to go after the aging process itself.


DR. McHUGH: I also want to thank you for that wonderful discussion, and I learned a lot from it. And I'm just not sure how I'm going to phrase this, but I think you and I, and perhaps all of us are in agreement that we want to do away with the things that impair our old people, which may well include, after all, Alzheimer's Disease. Alzheimer's Disease is a specific disorder, and we may be able to postpone its onset. Instead of having a 65 year old average age, we might be able to make it 95 or 100 before it comes in, in which case it would move things along.

On the other hand, so there wouldn't be any ethical problem, it seems to me, to work on improving that. The real issue is whether we're wasting time and effort in the ultimate striving for something which is intrinsically limited, the thing that both of you spoke about at the beginning, that there is an intrinsic limit to what we are. And I would like to tell you a little point that kind of makes that clear from the opposite end; that is, how do you define a child prodigy, that is somebody who knows at 40 what he knew at 8, because you get smart but you don't — you know, there's a limit to what you can do. And similarly here, there may be a limit, after all, to what we want. We want an age period which, again, it would be nice to be as long as it could be, but during which time the health was rosy, and the people were enjoying even their limited capacities. So just as you showed us that the mile run is not going to — has a natural limit, fundamentally out of the muscles and engineering of our body, are you agreed, and is aging research now agreed that listen, fundamentally there's a limit to this longevity business, and we ought to — we've got there now. Science has told us what that is, and now we just ought to be working on correcting the things which burden us from childhood to the end.

DR. OLSHANSKY: Well, no. I would certainly not suggest that by any means. And this issue of a limit, I would be careful about. I mean, I completely agree, there are clearly constraints to the duration of life, many of which I discussed during the presentation. There are biomechanical constraints to the way in which the body is constructed. There are biochemical constraints to the way in which our cells operate. But that doesn't mean we can't intervene in these processes. And, in fact, the approach that we're taking, in a way is the one that's going to permit many more of these age-associated problems to be expressed; which is precisely the reason why aging should be the enemy, not death. Going after the aging process itself, I think is fundamental.

It was one of the primary conclusions that we came to in our position statement on human aging, is that we need to attack the aging process itself. We haven't, you know — again, this issue of how much longer we can live I think should not necessarily be an important part of our discourse. It's trying to push back the envelope of the things that we don't like to see.

As you said, using Alzheimer's as an example, if we could push it back 25 years, the time in which it expressed itself, you could say the same thing about Osteoarthritis and Osteoporosis, and vision and hearing impairments, and the major fatal diseases, if we could push them back, if we could delay them, it would have a dramatic positive impact. And I don't know if we would necessarily live longer, but it would be a huge benefit to society.

DR. McHUGH: Oh, I absolutely agree, and so then you would accept then, if we could push all those back to 100, and say well listen, 100 is where we're going to get to and that would be it, and not worry about whether we're going to get to 102.

DR. OLSHANSKY: Right. Yes.

CHAIRMAN KASS: Let me join in since I was on queue, and partly to address Michael's question. And this is not as coherent as it will be, Michael, once I listen to this discussion and realize the various things that one might have thought to say.

First of all, it seems to me if you take by what you mean by an ethical question, not is it moral or immoral, or does it violate some rule that we have before us, but is it good, then it's perfectly clear that what's under discussion here is whether it's good to proceed in the direction that this research points us to. And there's some dispute about what it is that it's pointing us to, whether it really is retardation of senescence with only modest increases of the possible life span, potential species life span if I've got it right, or whether these things are linked. And more is better, if I understand my friend Charles. I mean, life is good, and the healthier and the longer, the better.

Second, and this is one of the reasons why it's interesting to take this topic up for us, is the people who are doing the research, very exciting research, talk at most about the possible health benefits that could come from this research, but declare themselves absolutely agnostic on the larger questions of what this would mean for the broader society, whether it has to do with work, retirement, education, opportunities for relations amongst the generations, the perception of time which is very different from the gift of time. And I have a passage from a wise physician I want to introduce in the discussion. And this is one of those areas where this is kind of paradigmatic for a lot of this area.

We can agree that disease is bad and health is good, and life is good, and death is bad, and here's research which will contribute to the things known to be good. The side consequences, and they're not merely accidental consequences. They may be built-in consequences of success in this area, have — go well beyond the question of the state of health of the individuals, as has already been indicated by Mary Ann's question, by Dr. Olshansky's comments, and it seems to me that we have a circumstance, and Professor Austad — the paper he submitted for us to read was wonderfully polemical in the sense that it argued not only that this research was good, but that it was only various kinds of political obstacles that stood in the way of our doing what is really important to do. Yet, I'm not sure that if we were convening ourselves as a wise council charged with the decision as to whether to pursue this, and I'm not saying — I don't prejudge the answer, but I'm not sure that the answer that it might, in fact, retard senescence with or without dramatic increases in the maximum human life expectancy, I'm not sure we have the information to discuss that. So this is one of these areas where there's an area of research potentially profound in its importance, potentially profound in its importance, is pursued with — and let me say this with a kind of cheerful naivete about what it means.

It's not to say that it's wrong. I mean, I think there's a way in which one will be hope filled with respect, especially if you define the meaning of this in such a narrow way. Well, who wouldn't want to be rid of the need for dentures, and hearing aides, and I can't remember what the next point I was going to make, those sorts of things. But that's why I think this is — and this is a kind of window into a whole range of other things pursued for the same goal.

If you listen to the conversation, no one is interested in immortality, but everyone is interested in getting rid of the latest obstacle that stands in the way of either fitness, or of sticking around. And, therefore, that's partly why —

PROF. SANDEL: No, but that was my question. Fitness or sticking around, which is it? I'm trying to understand what the research is aiming at. That's the question.

CHAIRMAN KASS: But if I understood Dr. Austad's point, although Professor Olshansky suggests that at least with respect to the research on specific diseases, we're not doing anything with respect to senescence. But if I understood your point, that these things may very well be linked, that if you somehow retard senescence, whether you want it or not, you're getting increases in the maximum possible human life span, and you're buying the whole package.

Now you don't have to talk about immortality to think that the world would be a very different place if, in fact, there were not just centenarians around, but the centenarians were the norm. And if one talked about 120 or 150, or even 200, and I mean, there are reputable scientists who are talking this kind of language.

If I might just permit one — let me just read something which is not usually entered into this discussion. Let me mention as homework, we'll dig it out and send it around. There's a wonderful meditation on this question of the life cycle in Aristotle's Rhetoric. It's admittedly presented for the purpose of rhetorical speech, but he's got a wonderful presentation of the young, the old, and those in their prime, in which the crucial thing is not in the way the biology, but things having to do with the experience of life, and what it does to people's outlook.

Let me read one passage, if I might. This is from Eric Cassell, a physician, very wise physician. This is on "Death and the Physician", written over 30 years ago. "While the gift of life must surely be marked as a great blessing, the perception of time as stretching out endlessly before us is somewhat threatening. Many of us function best under deadlines and tend to procrastinate when time limits are not set. Thus, this unquestioned boon, the extension of life, and the renewal of the threat of premature death - sorry - and the removal of the threat of premature death carries with it an unexpected anxiety, the anxiety of an unlimited future." And here's the part that I especially like, and I'd be interested in the remarks of the young people who are with us.

"In the young, the sense of limitless time has apparently imparted not a feeling of limitless opportunity, but increased stress and anxiety, in addition to the anxiety which results from other modern freedoms, personal mobility, a wide range of occupational choice, and independence from the limitations of class and familial patterns of work. A certain aimlessness characterizes discussions about their own aspirations. The future is endless, and their inner demands seem minimal. Although it may be uncharitable say-so, they seem to be acting in a way best described as `childish', particularly in their lack of a time sense. They behave as though there were no tomorrow, or as though the time limits imposed by the biological facts of life had become so vague for them, as to be non-existent."

That's a mouthful, and it's debatable, but if you simply think about the end of life, and sort of fiddling around with what you do for the elderly, you're producing something that affects the whole perception of a life course for everybody. And since the generations are inter-linked, and since the perception of time affects how one chooses to live one's life, these are momentous things. I think not — and the study of the past century for all of its blessings, has some insights about what it would mean to continue these blessings, and add another 50 years.

I'm sorry for the sermonette, but this was intended to the two Michaels, as to why I think this is weighty and why it matters. It's not a question for immediate public policy. The research is going to go forward, but to think about it as simply an extension of more of the same without realizing that there have been hidden costs of the same for which we are now blessed, I think is to miss the opportunity that this kind of research offers for taking a look at lots of things that we've been doing, which is not to say that we shouldn't have done them, or that we shouldn't do this. But I think there is a kind of weightiness to this that is worth our attention.

DR. McHUGH: But, Leon, you say 50 years. That was my point. Is this a ridiculous idea to think that there would be 50 years added onto this?

CHAIRMAN KASS: Two-fold and three-fold increases in the worms, six of these genes in the mice, this is stuff we know for how many years? Less than ten years. And by the way, the insulin-like growth factor 1, that's the stuff that Dr. Sweeney was talking about here, and making super-mice and super-rats, in which Mike Sandel can compete favorably with his son on the baseball field at the age of 80.

DR. McHUGH: Yes. Well, if he can continue to play baseball up to age 80 but, you know, all ended at about 100, then I'm all for it. The real question here is whether we're tilting against something that has an intrinsic limit, that hence — you know, what I said about the prodigy really meant that we can all catch up with the prodigy by working hard between the ages of 8 and 40, and know what he knows then. And similarly — and we want to do that. We want to make that a possibility. But when we think about this outside limits as though they were accessible, instead of — it confronts the issue that the prodigy doesn't learn an awful lot more than what human beings can learn. We can't live longer than what human beings really can live.

CHAIRMAN KASS: Gil Meilaender, Bill, and then Mary Ann, and then I think we should probably —

PROF. MEILAENDER: Well, I'm not sure I am all for it, Paul. I want to come back to Mike and Mike's question a little bit also. I mean, although there's something a little peculiar, Michael, about you know, laying out two or three really important moral issues, and saying apart from these, what morally is at stake here? But immortality, which was one of them, isn't implicated in this research. I understand. But the question was, what are we interested in, fitness or sticking around, as you said. And I think Professor Olshansky said, and surely some others. I mean, Paul's comments have been agreeing that aging or senescence should be the enemy, and not death. And that's what I'm not sure I believe, actually.

I think that, in fact, something probably the contrary of that. I think that death is an enemy, which doesn't mean it should always be resisted. There are enemies to which one must submit on occasion, but I'm a lot less sure about aging. I love baseball. Would it really be so good if I were still playing at age 80, or would that suggest some sort of fundamental immaturity in me? I'm not sure.

PROF. SANDEL: Come on.

PROF. MEILAENDER: No, I'm serious. The notion of getting rid of all the burdens in life. I mean, you see, what we're really after here is to live perfectly fit right up until the moment of our death, and then to say okay. And say we'd really like to kind of control it and master it, and I understand that. And when my right elbow bothers me, as it's bothering me right now, I appreciate that, but I'm not sure that, you know, it's my soundest instincts that would uttered if that's what I wanted. So it seems to me that one of the moral questions that's at issue here is precisely whether certain kinds of very natural instincts that we have ought to be resisted, in a way. And one of those is that desire not see my capacities wane.

I'm not so sure that the waning of them is, in fact, in and of itself an enemy. There are aspects of it that are. I understand that, but not entirely. And so, you know, if that's — then I think there's a genuine question there about which we probably do not agree, and I wouldn't know what to call it, other than a moral question, unless, you know, a spiritual question in some ways, but it certainly is an important question.


DR. ROWLEY: Well, I'd like to come back to your use of the term "manufactured survival time", because that bothers me, in that it implies that there really is an appropriate or biologically relevant time for death. And that what we've somehow done has been able to trick the system so the people are living longer. And then what you cite are all the negatives, kidney failure, cancer, things of that sort. And I, as somebody who's 77 years old, believe that one of the remarkable things that's happened during my lifetime is that older people are much more healthy, I suspect, than they were in previous decades and previous centuries. And I think that to the extent that we can enhance this, which again is related to somehow learning how to control or diminish senescence, is a real goal. And so I think that the positive aspects of this should be emphasized more. And I would come again to what Charles said. Fortunately, in the United States, probably almost entirely due to Claude Pepper, we don't have the mandatory retirement that faced my talented colleagues in Europe, Japan and Australia, where they have to leave their countries and go elsewhere if they want to continue an intellectually productive life, so I think that we should be looking at the positive things, not the negative.

CHAIRMAN KASS: Would you like to comment?

DR. OLSHANSKY: Well, this question of manufactured survival time, that came from one of the articles that we had published. And this actually — I'm not sure we're in any disagreement at all. I mean, this is an idea — this issue is one that I've discussed many times with my students, I'll be honest, about what would happen hypothetically if we didn't have any medicine at all? We just took a human population. We raised them in an environment where they had optimum food, they exercised every day, you know, no stress at all, and we followed this population across time, and we observed the time at which death occurred.

What would the life expectancy of this population be? Now I don't know the answer to this question definitively, but I would assume that it would be significantly lower than it is today, the life expectancy that we observe today of 80 and about 75 for males, which is a suggestion that much of time that is being lived by individuals, whether young or old, and I'm 48, and I would have died in my early 20s had it not been for time manufactured for me by medical technology, and I suspect the same can be said for many people in the room, that medical technology has saved us.

I consider the notion of manufactured time as something that is good, that is desirable, that it saves us both at younger and at older ages, and I do not object to this by any means, which relates to the question you were asking earlier, do we not support the idea of going after many of these fatal diseases. We do. I do suggest that we go after them, so I think we're really not in disagree about this issue of manufactured survival time. And if, indeed, we can push out the — we can push back senescence, then I think many of the things that you're talking about in terms of a healthy, productive, vibrant older age is something that we will see more of. It's a desirable goal.

CHAIRMAN KASS: We've got time for just two, and then we'll break. Bill Hurlbut and Mary Ann.

DR. HURLBUT: While we've been talking, I've been thinking that if that old French lady were Strom Thurman's mother, she could have been there to celebrate the — she could have restrained Trent Lott. So I've also been thinking about Michael Sandel's thoughtful little essay. I don't know if you had a chance to read that, but concerning the gift of the givenness of nature, and how interesting this is. That here we are talking about a major alteration of at least the way things play out in the environment. We've altered dramatically the curves you've showed us, and yet somehow we have this underlying impression that the goodness of the givenness of nature is achieved by opening this scenario to further life span. And I feel it too, but what worries me little bit are a couple of issues that have already been touched here better than I could phrase them, but it might be called the coordinate integration of meaningful existence. And I see several conflicting impulses going on here at once.

I agree with Gil that I don't exactly think aging is the enemy. In fact, I'd like to go a little bit on Michael's side, and say there's something about the givenness of aging that might have some good things about it, but how do we sort out what those are, and in which to intervene, if we can? I want to be used up in life. I don't want to be on reserve, or alter myself in such a way that I'm preserved but not engaged as deeply as I can, meaningfully as I can in my life.

Another thing worries me about this, is that in the initiation of the Society for Reproductive Medicine, William Hazeltine is quoted in "Science Magazine", and you probably saw that, as saying something to the effect of the real goal of medicine is to live forever. Well, if that's a little bit like worrying whether a new kind of pole is going to allow a pole vaulter to vault right over the moon, but nonetheless, there is this impulse in human nature to try to get more of life, whatever kind of life it is, or more of a better life. And I look at some of the proposals being put on the table, stem cells growing organs, which would be a wonderful possibility, but you can see how some day we might end up having a whole visceral retread, so that our basic physiological support systems were — I mean, this would be the equivalent of what you said you couldn't do, that's taking the car into the shop.

And I guess, I'm just trying to say something general here. I think a moral life is a meaningful life. And that's an integrated life, and not just an integrated personal life, but an integrated social life. And I guess it keeps coming back to Michael's interesting question here, what is there about the givenness of nature that provides meaning, and could we disrupt that? And I guess what I'm really asking for is your deepest thoughts on this. You must think about this all the time, and what do you really think is going on here? Is there a worrisome realm here, and how do you see it? You said some, but how do you see it best playing out?

DR. OLSHANSKY: Well, I don't want you to get me wrong here when I talk about efforts to go after aging. I can see how some might interpret that in a negative light, as if there's something bad or wrong with individuals growing older. I know this is the point you've raised repeatedly. I will patently admit that all the smartest people I know are over the age of 75.

When we talk about going after the aging process itself, it's a celebration of what happens as we grow older. It's a way to enhance and extend the benefits that accrue with the passage of time. It is not — it should not be interpreted in a negative light. It should be interpreted in a positive light, as something that is desirable that we want to happen, and I view aging, and I was taught about aging from Bernice Newgarden at the University of Chicago, who addressed this issue quite extensively. It's something to be celebrated. It's something to be enjoyed. That's my personal — you know, my deepest personal feeling is that I would like to see this process. I would like to live as long as I can, as healthy as I can with my mental and physical faculties operating as efficiently as possible, for as long as possible. And as a society, I see us benefitting by our aging.

I know somebody mentioned earlier that, you know, we're about to go into a radical transformation in our society. We've already gone through a radical transformation in our society in the past century in terms of population aging, and we're still here. And we're better off for it, as far as I'm concerned. And all we're saying is that I think it's something to be enhanced, but we need to be aware of our current approach to medicine.

Having said all of that, I also want to make a related point. And I know it relates to many of the issues that you've been addressing here for a while, and that is, the technologies associated with aging or efforts to influence aging process are going to happen anyway. Regardless of whether you and I want to happen, the scientific research devoted to the issue of modifying the biological rate of aging will happen. I believe efforts, and there are a number of scientists who are creating companies where they intend to sell products to the public to influence the aging process, well-known scientists are doing this. And so whether you want it to happen or not, if indeed it does happen, it's probably going to come from one of these major scientists who have created these companies. And whether or not it extends duration of life dramatically, I don't know, but much like cloning, and much like many of these other issues that you're dealing with, the battle — I mean, people are going to battle against death. They are going to fight against aging, and developing these technologies are a fundamental part of the biological sciences. And it's going to happen whether we want it to or not, so being aware of the consequences of this, understanding what it means, I think is what many of us are really devoted to working on.

CHAIRMAN KASS: Thank you. The last question from Mary Ann Glendon.

PROF. GLENDON: This is just a comment, and I'll make it very brief, but I think we shouldn't leave this subject of longevity and the diseases of old age without reminding ourselves that we're discussing it in a part of the world where people are living much longer than they are in the majority of countries in the world, where the single biggest killer is still an infectious disease, Malaria. And to my mind, it's very hard to separate the political and economic questions from the moral and ethical questions concerning what is the broader society, and what are we doing with the allocation of resources?

CHAIRMAN KASS: Thank you very much. Our deep thanks to both of our visitors this morning for wonderful presentations, very engaging and open and illuminating discussion. We will adjourn and meet back here promptly at 2:00, where Dr. Lawrence Diller will be with us for an afternoon presentation. Thank you.

(Off the record 12:27 p.m.)

  - The President's Council on Bioethics -  
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