There are two paths to superlongevity: only one of them is good

Memento Mori Ivories

Looked at in the longer historical perspective we have already achieved something our ancestors would consider superlongevity. In the UK life expectancy at birth averaged around 37 in 1700. It is roughly 81 today. The extent to which this is a reflection of decreased child mortality versus an increase in the survival rate of the elderly I’ll get to a little later, but for now, just try to get your head around the fact that we have managed to nearly double the life expectancy of human beings in a little over two centuries.

By itself the gains we have made in longevity are pretty incredible, but we have also managed to redefine what it means to be old. A person in 1830 was old at forty not just because of averages, but by the conditions of his body. A revealing game to play is to find pictures of adults from the 19th century and try to guess their ages. My bet is that you, like myself, will consistently estimate the people in these photos to be older than they actually were when the picture was taken. This isn’t a reflection of their lack of Botox and Photoshop, so much as the fact that they were missing the miracle of modern dentistry, were felled, or at least weathered, by diseases which we now consider mere nuisances. If I were my current age in 1830 I would be missing most of my teeth and the pneumonia I caught a few years back would have surely killed me, having been a major cause of death in the age of Darwin and Dickens.

Sixty or even seventy year olds today are probably in the state of health that a forty year old was in the 19th century. In other words we’ve increased the healthspan, not just the lifespan. Sixty really is the new forty, though what is important is how you define “new”. Yet get passed eighty in the early 21st century and you’re almost right back in the world where our ancestors lived. Experiencing the debilitations of old age that is the fate of those of us lucky enough to survive through the pleasures of youth and middle age. The disability of the old is part of the tragic aspect of life, and as always when it comes to giving poetic shape to our comic/ tragic existence, the Greeks got to the essence of old age with their myth of Tithonus.

Tithonus was a youth who had the ill fortune of inspiring the love of the goddess of spring Eos. (Love affairs between gods and mortals never end well). Eos asked Zeus to grant the youth immortality, which he did, but, of course, not in the way Eos intended. Tithonus would never die, but he also would continue to age becoming not merely old and decrepit, but eventually shrivel away to a grasshopper hugging a room’s corner. It is best not to ask the gods for anything.

Despite our successes, those of us lucky enough to live into our 7th and 8th decades still end up like poor old Tithonus. The deep lesson of the ancient myth still holds- longevity is not worth as much as we might hope if not also combined with the health of youth, and despite all of our advances, we are essentially still in Tithonus’ world.

Yet perhaps not for long. At least if one believes the story told by Jonathan Weiner in his excellent book Long for this World.  I learned much about our quest for long life and eternal youth from Long for this World, both its religious and cultural history, and the trajectory and state of its science. I never knew that Jewish folklore had a magical city called Luz where the death unleashed in Eden was prevented from entering, and that existed until  all its inhabitants became so bored that they walked out from its walls and we struck down by the Angel of Death waiting eagerly outside.

I did not know that Descartes, who had helped unleash the scientific revolution, thought that gains in knowledge were growing so fast that he would live to be 1,000. (He died in 1650 at 54). I did not realize that two other key figures of the scientific revolution Roger and Francis Bacon (no relation) thought that science would restore us to the knowledge before the fall (prelapsarian) which would allow us to live forever, or the depth to which very different Chinese traditions had no guilt at all about human immorality and pursued the goal with all sorts of elixirs and practices, none of which, of course, worked. I was especially taken with the story of how Pennsylvania’s most famous son- Benjamin Franklin- wanted to be “pickled” and awoken a century later.

Reviewing the past, when even ancient Egyptian hieroglyphs offer up recipes for “guaranteed to work” wrinkle creams, shows us just how deeply human the longing for agelessness is. It wasn’t invented by Madison Avenue or Dr Oz if even the attempts to find a fountain of youth by the ancients seem no less silly than many of our own. The question, I suppose, is the one that most risks the accusation that one is a fool: “Is this time truly different?” Are we, out of all the generations that have come before us believing the discovery of the route to human “immortality” (and every generation since the rise of modern science has had those who thought so) actually the ones who will achieve this dream?

Long for this World is at its heart a serious attempt to grapple with this question and tries to give us a clear picture of longevity science built around the theoretical biologist, Aubrey de Grey, who will either go down in history as a courageous prophet of a new era of superlongevity, or as just another figure in our long history of thinking biological immortality is at our fingertips when all we are seeing is a mirage.

One thing we have on our ancestors who chased this dream is that we know much, much, more about the biology of aging. Darwinian evolution allowed us to be able to conceive non- poetic theories on the origins of death. In the 1880’s the German biologist, August Weismann in his essay “Upon the Eternal Duration of Life”, provided a kind of survival of the fittest argument for death and aging. Even an ageless creature, Weismann argued, would overtime have to absorb multiple shocks eventually end up disabled. The the longer something lives the more crippled and worn out it becomes. Thus, it is in the interest of the species that death exists to clear the world of these disabled- very damned German- the whole thing.

Just after World War II the biologist Peter Medawar challenged the view of  Weismann. For Medawar if you look at any species selective pressures are really only operating when the organism is young. Those who can survive long enough to breed are the only ones that really count when it comes to natural selection. Like versions of James Dean or Marilyn Monroe, nature is just fine if we exit the world in the bloom of youth- as long, that is, as we have passed our genes.

In other words, healthful longevity has not really been something that natural selection has been selecting most organisms for, and because of this it hasn’t been selecting against bad things that can happen to old organisms either, as we’re finding when, by saving people from heart attacks in their 50’s, we destin them to die of diseases that were rare or unknown in the past like Alzheimers. In a sense we’re the victim of natural selection not caring about the health of those past reproductive age or their longevity.

Well, this is only partly true. Organisms that live in conditions where survival in youth is more secure end up with stretched longevity for their size. Some bats can live decades when similar sized mice have a lifespan of only a couple of years. Tortoises can live for well over a century while alligators of the same weight live from 30-50 years.

Stretching healthful longevity is also something that occurs when you starve an animal. We’ve know for decades that lifespan (in other animals at least) can be increased through caloric restriction. Although the mechanism is unclear, the Darwinian logic is not. Under conditions of starvation it’s a bad idea to breed and the body seems to respond by slowing development waiting for the return of food and a good time to mate.

Thus, there is no such thing as a death clock, lifespan is malleable and can be changed if we just learn how to work the dials. We should have known this from our historical experience over the last two-hundred years in which we doubled the human lifespan, but now we know that nature itself does it all the time and not by, like we do , by addressing the symptoms of aging but by resetting the clock of life itself.

We might ourselves find it easy to reset our aging clock if there weren’t multiple factors that play a role in its ticking. Aubrey de Grey has identified seven- the most important of which (excluding cancerous mutations) are probably the accumulation of “junk” within cells and the development of harmful “cross links” between cells. Strange thing about these is that they are not something that suddenly appears when we are actually “old” but are there all along, only reaching levels when they become noticeable and start to cause problems after many decades. We start dying the day we are born.

As we learn in Long for This World, there is hope that someday we may be able to effectively intervene against all these causes of aging. Every year the science needed to do so advances. Yet as Aubrey de Grey has indicated, the greatest threat to this quest for biological immortality is something we are all too familiar with – cancer.

The possibility of developing cancer emerges from the very way our cells work. Over a lifetime our trillions of cells replicate themselves an even more mind bogglingly high number of times. It is almost impossible that every copying error will be caught before it takes on a life of its own and becomes a cancerous growth. Increasing lifespan only increases the amount of time such copying errors can occur.

It’s in Aubrey de Grey’s solution to this last and most serious of super-longevity’s medical hurdles that Weiner’s faith in the sense of that project breaks down, as does mine. De Grey’s cure for cancer goes by the name of WILT- whole body interdiction of the lengthening of telomeres. A great deal of the cancers that afflict human beings achieve their deadly replication without limit by taking control of the telomerase gene. De Grey’s solution is to strip every human gene of its telomeres, something that, even if successful in preventing cancerous growths, would also leave us without red and white blood cells. In order to allow us to live without these cells, de Grey proposes regular infusions of stem cells. What this leave us with would be a life of constant chemotherapy and invasive medical interventions just to keep us alive. In other words, a life when even healthy people relate to their bodies and are kept alive by medical interventions that are now only experienced by the terminally ill.

I think what shocks Weiner about this last step in SENS is the that it underscores just how radical the medical requirements of engineering superlongevity might become. It’s one thing to talk about strengthening the cell’s junk collector the lysosome by adding an enzyme or through some genetic tweak, it’s another to talk about removing the very cells and structures which define human biology, cells and platelets, which have always been essential for human life and health.

Yet, WILT struck me with somewhat different issues and questions. Here’s how I have come to understand it. For simplicities sake, we might be said to have two models of healthcare, both of which have contributed to the gains we have seen in human health and longevity since 1800. As is often noted, a good deal of this gain in longevity was a consequence of improving childhood mortality. Having less and less people die at the age of five drastically improves the average lifespan. We made these gains largely through public health: things like drastically improved sanitation, potable water, vaccinations, and, in the 20th century antibiotics.

This set of improvements in human health were cheap, “easy”, and either comprised of general environmental conditions, or administered at most annually- like the flu shoot. These features allowed this first model of healthcare to be distributed broadly across the population leading to increased longevity by saving the lives primarily of the young. In part these improvements, and above all the development of antibiotics, also allowed longevity increases from at older end of the scale, which although less pronounced than improvements in child mortality, are, nonetheless very real. This is my second model of healthcare and includes things everything from open heart surgery, to chemo and radiation treatments for cancer, to lifelong prescription drugs to treat chronic conditions.

As opposed to the first model, the second one is expensive, relatively difficult, and varies greatly among different segments of the population. My Amoxicillin and Larry Page’s Amoxicillin are the same, but the medical care we would receive to treat something like cancer would be radically different.

We actually are making greater strides in the battle against cancer than at any time since Nixon declared war on the scourge way back in the 1970’s. A new round of immunosuppressive drugs that are proving so successful against a host of different cancers that John LaMattina, former head of research and development for Pfizer has stated that “We are heading towards a world where cancer will become a chronic disease in much the same way as we have seen with diabetes and HIV.”

The problem is the cost which can range up to 150,000 per year. The costs of the new drugs are so expensive that the NHS has reduced the amount they are willing to spend on them by 30 percent. Here we are running up against the limits to second model of healthcare, a limit that at some point will force societies to choose between providing life preserving care for all, or only to those rich enough to afford it.

If the superlongevity project is going to be a progressive project it seems essential to me that it look like the first model of healthcare rather than the second. Otherwise it will either leave us with divergences in longevity within and between societies that make us long nostalgically for the “narrowness” of current gap between today’s poorest and richest societies, or it will bankrupt countries that seek to extend increased longevity to everyone.

This would require a u-turn from the trajectory of healthcare today which is dominated and distorted by the lucrative world of the second model. As an example of this distortion: the physicists, Paul Davies, is working on a new approach to cancer that involves attempting to attack the disease with viruses. If successful this would be a good example of model one. Using viruses (in a way the reverse of immunosuppressives) to treat cancer would likely be much cheaper than current approaches to cancer involving radiation, chemotherapy, and surgery due to the fact that viruses can self-replicate after being engineered rather than needing to be expensively and painstakingly constructed in drug labs. The problem is that it’s extremely difficult for Davies to get funding for such research precisely because there isn’t that much money to be made in it.

In an interview about his research, Davies compared his plight to how drug companies treat aspirin. There’s good evidence to show that plain old aspirin might be an effective preventative against cancer. Sadly, it’s almost impossible to find funding for large scale studies of aspirin’s efficacy in preventing cancer because you can buy a bottle of the stuff for a little over a buck, and what multi-billion dollar pharmaceutical company could justify profit margins as low as that?

The distortions of the second model are even more in evidence when it comes to antibiotics. Here is one of the few places where the second model of healthcare is dependent upon the first. As this chilling article by Maryn Mckenna drives home we are in danger of letting the second model lead to the nightmare of a sudden sharp reversal of the health and longevity gains of the last century.

We are only now waking up to the full danger implicit in antibiotic resistance. We’ve so over prescribed these miracle treatments both to ourselves and our poor farms animals who we treat as mere machines and “grow” in hellish sanitary conditions that bacteria have evolved to no longer be treatable with the suite of antibiotics we have, which are now a generation old, or older. If you don’t think this is a big deal, think about what it means to live in a world where a toothache can kill you and surgeries and chemotherapy can no longer be performed. A long winter of antibiotic resistance would just mean that many of our dreams of superlongevity this century would be moot. It would mean many of us might die quite young from common illnesses, or from surgical and treatment procedures that have combined given us the longevity we have now.

Again, the reason we don’t have alternatives to legacy antibiotics is that pharmaceutical companies don’t see any profit in these as opposed to, say Viagra. But the other part of the reason for their failure, is just as interesting. It’s that we have overtreated ourselves because we find the discomfort of being even mildly sick for a few days unbearable. It’s also because we want nature, in this case our farm animals, to function like machines. Mechanical functioning means regularity, predictability, standardization and efficiency and we’ve had to so distort the living conditions, food, and even genetics of the animals we raise that they would not survive without our constant medical interventions, including antibiotics.

There is a great deal of financial incentive to build solutions to human medical problems around interminable treatments rather than once and done cures or something that is done only periodically. Constant consumption and obsolescence guarantees revenue streams.  Not too long ago, Danny Hillis, who I otherwise have the deepest respect for, gave an interview on, among other things, proteomics, which, for my purposes here, essentially means the minute analysis of bodily processes with the purpose of intervening the moment things begin to go wrong- to catch diseases before they cause us to exhibit symptoms. An audience member asked a thought provoking question, which when followed up by the interviewer Alexis Madrigal, seemed to leave the otherwise loquacious Hillis, stumped. How do you draw the line between illness without symptoms and what the body just naturally does? The danger is you might end up turning everyone, including the healthy, into “patients” and “profit centers”.

We already have a world where seemingly healthy people needed to constantly monitor and medicate themselves just to keep themselves alive, where the body seems to be in a state of almost constant, secret revolt. This is the world as diabetics often experience it, and it’s not a pretty one.  What I wonder is if, in a world in which everyone sees themselves as permanently sick- as in the process of dying- and in need of medical intervention to counter this sickness if we will still remember the joy of considering ourselves healthy? This is medicine becoming subsumed under our current model of consumption.   

Everyone, it seems, has woken up to the fact that consumer electronics has the perfect consumption sustaining model. If things quickly grow “old” to the point where they no longer work with everything else you own, or become so rare that one is unable to find replacement parts, then one if forced to upgrade if merely to insure that your stuff still works. Like the automotive industry, healthcare now seems to be embracing technological obsolescence as a road to greater profitability. Insurance companies seem poised to use devices like the Apple watch to sort and monitor customers, but that is likely only the beginning.

Let me give you my nightmare scenario for a world of superlongevity. It’s a world largely bereft of children where our relationship to our bodies has become something like the one we have with our smart phones, where we are constantly faced with the obsolescence of the hardware and the chemicals, nano-machines and genetically engineered organisms under our own skins and in near continuous need of upgrades to keep us alive. It is a world where those too poor to be in the throes of this cycle of upgrades followed by obsolescence followed by further upgrades are considered a burden and disposable in  the same way August Weismann viewed the disabled in his day.  It’s a world where the rich have brought capitalism into the body itself, an individual life preserved because it serves as a perpetual “profit center”.

The other path would be for superlongevity to be pursued along my first model of healthcare focusing its efforts on understanding the genetic underpinnings of aging through looking at miracles such as the bowhead whale which can live for two centuries and gets cancer no more often than we do even though it has trillions more cells than us. It would focus on interventions that were cheap, one time or periodic, and could be spread quickly through populations. This would be a progressive superlongevity.  If successful, rather than bolster, it would bankrupt much of the system built around the second model of healthcare for it would represent a true cure rather than a treatment of many of the diseases that ail us.

Yet even superlongevity pursued to reflect the demands for justice seems to confront a moral dilemma that seems to be at the heart of any superlongevity project. The morally problematic features of superlongevity pursued along the second model of healthcare is that it risks giving long life only to the few. Troublingly, even superlongevity pursued along the first model of healthcare ends up in a similar place, robbing from future generations of both human beings and other lifeforms the possibility of existing, for it is very difficult to see how if a near future generation gains the ability to live indefinitely how this new state could exist side-by-side with the birth of new people or how such a world of many “immortals” of the types of highly consuming creatures we are is compatible with the survival of the diversity of the natural world.

I see no real solution to this dilemma, though perhaps as elsewhere, the limits of nature will provide one for us, that we will discover some bound to the length of human life which is compatible with new people being given the opportunity to be born and experience the sheer joy and wonder of being alive, a bound that would also allow other the other creatures with whom we share our planet to continue to experience these joys and wonders as well. Thankfully, there is probably some distance between current human lifespans and such a bound, and thus, the most important thing we can do for now, is try to ensure that research into superlongevity has the question of sustainable equity serve as its ethical lodestar.

 Image: Memento Mori, South Netherlands, c. 1500-1525, the Thomson collection

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